{"id":26924,"date":"2023-06-30T09:00:42","date_gmt":"2023-06-30T06:00:42","guid":{"rendered":"https:\/\/www.klimikdergisi.org\/?p=26924"},"modified":"2026-02-14T23:01:13","modified_gmt":"2026-02-14T20:01:13","slug":"klimik-bruselloz-tani-ve-tedavi-rehberi","status":"publish","type":"post","link":"https:\/\/www.klimikdergisi.org\/tr\/2023\/06\/30\/klimik-bruselloz-tani-ve-tedavi-rehberi\/","title":{"rendered":"T\u00fcrk Klinik Mikrobiyoloji ve \u0130nfeksiyon Hastal\u0131klar\u0131 Derne\u011fi Kan\u0131ta Dayal\u0131 Bruselloz Tan\u0131 ve Tedavi Klinik Uygulama Rehberi, 2023"},"content":{"rendered":"<p class=\"p1\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2024\/09\/p_1277Artboard-1.png\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-29962 alignnone\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2024\/09\/p_1277Artboard-1.png\" alt=\"\" width=\"29\" height=\"29\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2024\/09\/p_1277Artboard-1.png 512w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2024\/09\/p_1277Artboard-1-260x260.png 260w\" sizes=\"auto, (max-width: 29px) 100vw, 29px\" \/> <\/a>Bu makaleye ili\u015fkin\u00a0<span style=\"color: #ff0000;\"><strong><span class=\"s1\"><a href=\"https:\/\/www.klimikdergisi.org\/tr\/2026\/02\/14\/duzeltme-klimik-kanita-dayali-bruselloz-tani-ve-tedavi-klinik-uygulama-rehberi-2023\/\">bir d\u00fczeltme<\/a><\/span><\/strong><\/span> 14 \u015eubat 2026\u2019da yay\u0131nland\u0131: <a href=\"https:\/\/www.klimikdergisi.org\/tr\/2026\/02\/14\/duzeltme-klimik-kanita-dayali-bruselloz-tani-ve-tedavi-klinik-uygulama-rehberi-2023\/\">https:\/\/doi.org\/10.36519\/kd.2026.5533<\/a><\/p>\n<hr \/>\n<h2 class=\"p1\">\u00d6NER\u0130LER\u0130N \u00d6ZET\u0130<\/h2>\n<h4 class=\"p2\">1- Brusellozdan ku\u015fkulan\u0131lan hastalarda Rose Bengal testinin tan\u0131daki yeri nedir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Rose Bengal (RB) testinin bruselloz tan\u0131s\u0131nda duyarl\u0131l\u0131\u011f\u0131 y\u00fcksektir. Temas \u00f6yk\u00fcs\u00fc ve uyumlu semptomlar\u0131 olan hastalarda h\u0131zl\u0131 tan\u0131 testi olarak kullan\u0131lmas\u0131 \u00f6nerilir (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>). Yap\u0131lan meta-analizlerinde testin \u00f6zg\u00fcll\u00fc\u011f\u00fc de y\u00fcksek bulunmu\u015ftur, ancak de\u011ferlendirilen kontrol gruplar\u0131 uygun olmad\u0131\u011f\u0131 i\u00e7in, mevcut veriler bruselloz tan\u0131s\u0131nda tek ba\u015f\u0131na kullan\u0131lmas\u0131 konusunda yeterli de\u011fildir. Antikor taramaya y\u00f6nelik bir test olmas\u0131 nedeniyle hastal\u0131\u011f\u0131n erken d\u00f6nemlerinde yalanc\u0131 negatiflik olabilece\u011finin de ak\u0131lda tutulmas\u0131 \u00f6nerilir (<i>\u00c7ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<\/p>\n<h4 class=\"p2\">2- Brusellozdan ku\u015fkulan\u0131lan hastalarda Wright standart t\u00fcp agl\u00fctinasyon testinin tan\u0131daki yeri nedir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Brusellozdan ku\u015fkulan\u0131lan hastalarda Wright standart t\u00fcp agl\u00fctinasyon (STA) testinin \u22651:160 titrasyonda pozitifli\u011finin, bruselloz tan\u0131s\u0131 i\u00e7in duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fc y\u00fcksek bulunmu\u015ftur. Erken tedavi ba\u015flanmas\u0131n\u0131n gerekli oldu\u011fu durumlarda h\u0131zl\u0131 tan\u0131da veya k\u00fclt\u00fcr\u00fcn yap\u0131lamad\u0131\u011f\u0131 durumlarda tan\u0131da Wright STA testi kullan\u0131labilir. Brusellozdan ku\u015fkulan\u0131lan hastalarda RB testi pozitif saptand\u0131\u011f\u0131 durumlarda tan\u0131n\u0131n, daha \u00f6zg\u00fcl olmas\u0131 nedeniyle, Wright STA testi ile do\u011frulanmas\u0131 \u00f6nerilir (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<\/p>\n<p class=\"p3\">Brusella endokarditi olan hastalarda, Wright STA\u2019n\u0131n, \u22651:1280 titrede pozitif olmas\u0131 mortalite ile ili\u015fkili bulunmu\u015ftur. Bu nedenle bu grup hastalarda ayn\u0131 zamanda, prognozu \u00f6ng\u00f6rmek i\u00e7in de Wright STA testinin kullan\u0131lmas\u0131 d\u00fc\u015f\u00fcn\u00fclebilir (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, zay\u0131f \u00f6neri<\/i>).<\/p>\n<h4 class=\"p2\">3- Brusellozdan ku\u015fkulan\u0131lan hastalarda enzim i\u015faretli imm\u00fcn deney (ELISA) temelli testlerin tan\u0131daki yeri nedir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Brusellozdan ku\u015fkulan\u0131lan ve RB testi pozitif olan hastalarda do\u011frulama amac\u0131yla STA testi yerine ELISA temelli testler de kullan\u0131labilir. Tan\u0131da ELISA temelli testler kullan\u0131lacaksa IgM ve IgG testlerinin birlikte kullan\u0131lmas\u0131 \u00f6nerilir (<i>\u00c7ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<\/p>\n<h4 class=\"p2\">4- Brusellozdan ku\u015fkulan\u0131lan hastalarda polimeraz zincir reaksiyonu (PCR) temelli testlerin tan\u0131daki yeri nedir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Bruselloz tan\u0131s\u0131nda PCR temelli testlerin duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fc y\u00fcksektir, ancak pahal\u0131 olmalar\u0131, deneyimli personel ve teknik donan\u0131m gerektirmeleri nedeniyle ilk a\u015famada tan\u0131 testi olarak kullan\u0131m\u0131 \u00f6nerilmez. Wright STA testinin negatif \u00e7\u0131kmas\u0131na kar\u015f\u0131l\u0131k klinik ku\u015fkunun devam etti\u011fi ve k\u00fclt\u00fcr sonucunun beklenmesinin tan\u0131 ve tedaviyi geciktirerek hastada olumsuz sonu\u00e7lara yol a\u00e7abilece\u011fi d\u00fc\u015f\u00fcn\u00fcld\u00fc\u011f\u00fc durumlarda bruselloz tan\u0131s\u0131 koymak i\u00e7in PCR temelli testlerin kullan\u0131m\u0131 d\u00fc\u015f\u00fcn\u00fclebilir <i>(D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri)<\/i>.<\/p>\n<h4 class=\"p2\">5- N\u00f6robruselloz tan\u0131s\u0131nda hangi tan\u0131sal testler tercih edilmelidir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> N\u00f6robrusellozdan ku\u015fkulan\u0131lan hastalarda kesin tan\u0131 i\u00e7in, beyin omurilik s\u0131v\u0131s\u0131 (BOS)\u2019nda h\u00fccre say\u0131m\u0131, protein ve glukoz \u00f6l\u00e7\u00fcmleri, kan ve BOS k\u00fclt\u00fcr\u00fc, serum ve BOS\u2019ta Wright STA testi ve\/veya Coombs\u2019lu Wright STA testlerinin hepsinin bir arada yap\u0131lmas\u0131 \u00f6nerilir <i>(\u00c7ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri).<span class=\"Apple-converted-space\">\u00a0<\/span><\/i><\/p>\n<p class=\"p3\">Az say\u0131da do\u011frulanm\u0131\u015f n\u00f6robruselloz tan\u0131s\u0131 alan olgudan elde edilen verilerde, BOS\u2019ta ELISA ile <i>Brucella<\/i> spp. IgM ve\/veya IgG bak\u0131lmas\u0131n\u0131n, BOS Wright STA testine k\u0131yasla daha duyarl\u0131 oldu\u011fu g\u00f6r\u00fcld\u00fc\u011f\u00fcnden, ula\u015f\u0131labilen yerlerde BOS\u2019ta Wright STA yerine ELISA IgM\/IgG testinin tercih edilmesi d\u00fc\u015f\u00fcn\u00fclebilir <i>(\u00c7ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, zay\u0131f \u00f6neri)<\/i>.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h4 class=\"p2\">6- Bruselloz tedavisinde alt\u0131 haftal\u0131k tedavi s\u00fcresi d\u00f6rt haftal\u0131k tedavi s\u00fcresinden \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Komplike bruselloz olgular\u0131n\u0131n (endokardit, n\u00f6robruselloz ve spondilit) d\u0131\u015flanarak bruselloz tedavi s\u00fcresinin kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131 \u00e7al\u0131\u015fmalar\u0131n meta-analizinde, d\u00f6rt haftal\u0131k rejimlerle kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, alt\u0131 haftal\u0131k antimikrobiyal tedavilerle relaps geli\u015fme riski daha d\u00fc\u015f\u00fck bulunmu\u015ftur. Akut bruselloz tan\u0131s\u0131 konulan hastalarda alt\u0131 haftal\u0131k tedavi kullan\u0131lmas\u0131 \u00f6nerilir <i>(D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<\/p>\n<h4 class=\"p2\">7-Bruselloz tedavisinde doksisiklin + streptomisin kombinasyonu, doksisiklin + rifampisin kombinasyonundan \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Akut bruselloz tan\u0131s\u0131 konulan hastalarda tedavi rejimlerinin kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131 \u00e7al\u0131\u015fmalar\u0131n meta-analizinde doksisiklin-streptomisin (DOX-STREP) rejimi, doksisiklin-rifampisin (DOX-RIF) rejimine g\u00f6re daha d\u00fc\u015f\u00fck tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 ve relapsla ili\u015fkili bulunmu\u015ftur. Her iki tedavi rejimi aras\u0131nda yan etki geli\u015fimi a\u00e7\u0131s\u0131ndan fark saptanmam\u0131\u015ft\u0131r. Kullan\u0131m zorlu\u011fu ve uyum sorunu ya\u015famayacak akut bruselloz tan\u0131s\u0131 konulan hastalarda \u00f6ncelikle DOX-STREP kombinasyonunun kullan\u0131lmas\u0131 \u00f6nerilir <i>(D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, zay\u0131f \u00f6neri)<\/i>.<\/p>\n<h4 class=\"p2\">8-Bruselloz tedavisinde doksisiklin + streptomisin kombinasyonu, doksisiklin + gentamisin kombinasyonundan \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Akut bruselloz tedavisinde DOX-STREP kombinasyonunun, doksisiklin+gentamisin (DOX-GEN) kombinasyonuna, tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, relaps ve yan etki geli\u015fimi a\u00e7\u0131s\u0131ndan \u00fcst\u00fcnl\u00fc\u011f\u00fc yoktur. Tedavide DOX ile kombinasyonda STREP veya GEN\u2019den birinin tercih edilmesi \u00f6nerilir <i>(Orta kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<\/p>\n<h4 class=\"p2\">9-Bruselloz tedavisinde kinolon grubu antimikrobik i\u00e7eren kombinasyonlar, kinolon i\u00e7ermeyen kombinasyonlardan \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri: <\/strong>Akut bruselloz tedavi rejimlerini kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n meta-analizinde kinolon grubu antimikrobikleri i\u00e7eren kombinasyonlar\u0131n, i\u00e7ermeyen kombinasyonlara g\u00f6re, tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, relaps ve yan etki geli\u015fimi a\u00e7\u0131s\u0131ndan \u00fcst\u00fcn olmad\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Ek olarak son y\u0131llarda kinolon grubu antimikrobiklerle ilgili artan g\u00fcvenlik endi\u015feleri nedeniyle,<b> <\/b>akut bruselloz tedavisinde<b> <\/b>kinolon grubu antimikrobik i\u00e7eren kombinasyonlar\u0131n \u00f6ncelikli olarak tercih edilmemesi \u00f6nerilir. Bruselloz tedavisinde kinolonlar\u0131n, sadece ilk se\u00e7enek ila\u00e7lar\u0131n [DOX, RIF, GEN, STREP] yan etki, ila\u00e7 etkile\u015fimi gibi herhangi bir nedenle kullan\u0131lamad\u0131\u011f\u0131 durumlarda kombinasyonun bir bile\u015feni olarak d\u00fc\u015f\u00fcn\u00fclmesi \u00f6nerilir <i>(\u00c7ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri).<\/i><\/p>\n<h4 class=\"p2\">10-Bruselloz tan\u0131s\u0131 konmu\u015f gebelerde rifampisin + seftriakson tedavisi, rifampisin + trimetoprim-s\u00fclfametoksazol tedavisine g\u00f6re daha etkili midir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Bruselloz tan\u0131s\u0131 konmu\u015f gebelerin tedavisinde farkl\u0131 kombinasyonlar\u0131 kar\u015f\u0131la\u015ft\u0131ran olgu serilerinin analizinde RIF + trimetoprim-s\u00fclfametoksazol (<span class=\"s1\">TMP-SMX)<\/span> kombinasyonuyla, RIF+seftriakson (CRO) kombinasyonu aras\u0131nda gebelik komplikasyonu geli\u015fimi a\u00e7\u0131s\u0131ndan bir fark belirlenmemi\u015ftir. Gebe bruselloz olgular\u0131n\u0131n tedavisinde RIF+<span class=\"s1\">TMP-SMX<\/span> veya RIF+CRO kombinasyonlar\u0131ndan birinin kullan\u0131lmas\u0131 \u00f6nerilmekle birlikte <span class=\"s1\">TMP-SMX kombinasyonunun<\/span> birinci trimesterde teratojenik etki, son trimesterde ise kernikterus geli\u015ftirme riski bulunmas\u0131 nedeniyle birinci ve \u00fc\u00e7\u00fcnc\u00fc trimesterde RIF+CRO kombinasyonunun tercih edilmesi \u00f6nerilir <i>(<\/i>\u00c7<i>ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, zay\u0131f \u00f6neri)<\/i>.<\/p>\n<h4 class=\"p2\">11-N\u00f6robruselloz tedavisinde seftriakson i\u00e7eren kombinasyon rejimi, seftriakson i\u00e7ermeyen rejime g\u00f6re daha etkili midir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Tedavi rejimlerinin kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131 n\u00f6robruselloz olgu serilerinin \u201cindividual participant data\u201d (IPD) meta-analizinde tedaviye CRO eklenmesinin tedavi ba\u015far\u0131s\u0131n\u0131 anlaml\u0131 olarak art\u0131rd\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. N\u00f6robruselloz tedavisinde standart tedaviye CRO eklenmesi \u00f6nerilir <i>(D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g<\/i>\u00fc\u00e7l\u00fc \u00f6neri).<\/p>\n<h4 class=\"p2\">12-<i>Brucella <\/i>spp. endokarditi olan hastalarda, tan\u0131 an\u0131ndaki Wright STA testi titresi olumsuz sonu\u00e7lar\u0131 g\u00f6sterir mi?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp.<b> <\/b>endokarditi olgular\u0131n\u0131n IPD meta-analizinde, tan\u0131 an\u0131ndaki Wright agl\u00fctinasyon titresinin 1\/1280\u2019in \u00fczerinde olmas\u0131n\u0131n, \u00f6l\u00fcm riskini belirgin olarak art\u0131rd\u0131\u011f\u0131<span class=\"Apple-converted-space\">\u00a0 <\/span>belirlenmi\u015ftir. <i>Brucella<\/i> spp. endokarditi olan hastalarda, tan\u0131 an\u0131ndaki Wright STA testi titresinin 1\/1280\u2019in \u00fczerinde olmas\u0131 \u00f6l\u00fcm riskinin y\u00fcksek olabilece\u011fini \u00f6ng\u00f6rmek amac\u0131yla kullan\u0131labilir <i>(D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, zay\u0131f \u00f6neri)<\/i>.<\/p>\n<h4 class=\"p2\">13-<i>Brucella <\/i>spp. endokarditi olan hastalarda, 3\u2019l\u00fc antimikrobik tedavi rejimleri, 2\u2019li antimikrobik tedavi rejimlerinden daha \u00fcst\u00fcn m\u00fcd\u00fcr?<span class=\"Apple-converted-space\">\u00a0<\/span><\/h4>\n<p class=\"p3\"><strong>\u00d6neri: <\/strong><i>Brucella<\/i> spp.<b> <\/b>endokarditi olgular\u0131n\u0131n IPD meta-analizinde, 2\u2019li antimikrobik tedavi alanlarda \u00f6l\u00fcm oran\u0131, istatistiksel olarak anlaml\u0131 olmasa da 3\u2019l\u00fc tedavi alanlardan daha y\u00fcksek<span class=\"Apple-converted-space\">\u00a0 <\/span>bulunmu\u015ftur.<span class=\"Apple-converted-space\">\u00a0 <\/span>\u00d6l\u00fcm d\u0131\u015f\u0131 istenmeyen etkiler birle\u015fik sonlan\u0131m\u0131 (rek\u00fcrans veya istenmeyen ila\u00e7 etkileri veya yeniden hastane yat\u0131\u015f\u0131 veya hastane yat\u0131\u015f\u0131nda postoperatif komplikasyonlar veya bir y\u0131l i\u00e7inde yeniden ameliyat edilmede) 2\u2019li antimikrobik tedavi alanlarda 3\u2019l\u00fc tedavi alanlardan anlaml\u0131 olarak daha y\u00fcksek bulunmu\u015ftur. Bir di\u011fer komplike bruselloz olan spondilodiskit \u00e7al\u0131\u015fmalar\u0131n\u0131n meta-analizinde de 3\u2019l\u00fc tedaviler daha \u00fcst\u00fcn bulunmu\u015ftur. <i>Brucella <\/i>spp. endokarditi olgular\u0131n\u0131n tedavisinde 3\u2019l\u00fc antimikrobik tedavi rejimleri \u00f6nerilir <i>(D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>)<i>.<\/i> <span class=\"Apple-converted-space\">\u00a0 \u00a0<\/span><\/p>\n<h4 class=\"p2\">14-<i> Brucella <\/i>spp. endokarditi olan hastalarda aminoglikozid i\u00e7eren ve i\u00e7ermeyen tedaviler aras\u0131nda olumsuz sonu\u00e7lar a\u00e7\u0131s\u0131ndan fark var m\u0131d\u0131r?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp.<span class=\"Apple-converted-space\">\u00a0 <\/span>endokarditi olgular\u0131n\u0131n IPD meta-analizinde,<span class=\"Apple-converted-space\">\u00a0 <\/span>aminoglikozid i\u00e7eren rejimlerle tedavi edilenlerde \u00f6l\u00fcm oran\u0131 belirgin olarak daha d\u00fc\u015f\u00fck, ancak ba\u015fta istenmeyen ila\u00e7 etkileri olmak \u00fczere \u00f6l\u00fcm d\u0131\u015f\u0131 istenmeyen sonlan\u0131mlar\u0131n geli\u015fme riski belirgin olarak daha y\u00fcksek bulunmu\u015ftur. <i>Brucella<\/i> spp. endokarditlerinde aminoglikozid i\u00e7eren rejimlerle tedavi \u00f6nerilir, ancak aminoglikozid verilen hastalarda, nefrotoksisite y\u00f6n\u00fcnden yak\u0131n izlem yap\u0131lmal\u0131, ek nefrotoksik ajanlar\u0131n kullan\u0131m\u0131ndan ka\u00e7\u0131n\u0131lmal\u0131d\u0131r <i>(D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h4 class=\"p2\">15- <i>Brucella<\/i> spp. endokarditi olan hastalarda kapak cerrahisi uygulamas\u0131n\u0131n olumsuz sonu\u00e7lar\u0131 azaltmada etkisi var m\u0131d\u0131r?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp.<b> <\/b>endokarditi olgular\u0131n\u0131n IPD meta-analizinde, kapak cerrahisi uygulanmas\u0131n\u0131n \u00f6l\u00fcm riskini belirgin olarak azaltt\u0131\u011f\u0131 belirlenmi\u015ftir. <i>Brucella<\/i> spp. endokarditi tan\u0131s\u0131 konulan hastalarda, infektif endokardit ekipleri taraf\u0131ndan acil veya elektif kapak cerrahisi indikasyonlar\u0131<span class=\"Apple-converted-space\">\u00a0 <\/span>dikkatle de\u011ferlendirilerek, uygun bulunan hastalarda cerrahinin<span class=\"Apple-converted-space\">\u00a0 <\/span>yap\u0131lmas\u0131 \u00f6nerilir <i>(D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h4 class=\"p2\">16-<i> Brucella<\/i> spp. endokarditi olan hastalarda \u22643 ayl\u0131k antimikrobiyal tedaviler ile &gt;3 ayl\u0131k tedaviler aras\u0131nda olumsuz sonu\u00e7lar a\u00e7\u0131s\u0131ndan fark var m\u0131d\u0131r?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp.<b> <\/b>endokarditi olgular\u0131n\u0131n IPD meta-analizinde, \u00f6len hastalar\u0131n hemen hepsinin ilk \u00fc\u00e7 ayda hayat\u0131n\u0131 kaybetti\u011fi g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Bu nedenle tedavi s\u00fcresinin \u00f6l\u00fcm \u00fczerine etkisi belirlenememi\u015ftir.<span class=\"Apple-converted-space\">\u00a0 <\/span>Ayn\u0131 analizde &gt;3 ay tedavi alan ve almayan hastalar aras\u0131nda \u00f6l\u00fcm d\u0131\u015f\u0131 istenmeyen sonlan\u0131mlar\u0131n s\u0131kl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan bir fark bulunamam\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span><i>(Bilgi bo\u015flu\u011fu nedeniyle \u00f6neri yap\u0131lamaz)<\/i>.<\/p>\n<h4 class=\"p2\">17- <i>Brucella<\/i> spp. spondilodiskiti tedavisinde doksisiklin + streptomisin rejimi, doksisiklin + rifampisin rejimine \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><span class=\"s2\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp. spondilodiskiti olan hastalarda DOX+STREP rejimini DOX+RIF\u2019le kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n kan\u0131t d\u00fczeylerinin ve kalitesinin yetersiz oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella<\/i> spp. spondilodiskiti tedavisinde antimikrobiyal tedavi rejimi konusunda kan\u0131ta dayal\u0131 \u00f6neri yap\u0131labilmesi m\u00fcmk\u00fcn de\u011fildir, bu konuda bilgi bo\u015flu\u011fu vard\u0131r. Akut bruselloz tedavi rejimlerini kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n meta-analizinde STREP i\u00e7eren rejimin daha etkili bulunmu\u015f olmas\u0131 nedeniyle, ek olarak rehber grubunda yer alan uzmanlar\u0131n da uzla\u015f\u0131s\u0131yla, <i>Brucella<\/i> spp. spondilodiskiti tedavisinde de DOX+STREP rejimine \u00f6ncelik verilmesi \u00f6nerilmi\u015ftir (<i>Bilgi bo\u015flu\u011fu<\/i>).<\/span><\/p>\n<h4 class=\"p2\">18- <i>Brucella<\/i> spp. spondilodiskiti tedavisinde 3\u2019l\u00fc antimikrobiyal kombinasyon rejimleri, 2\u2019li kombinasyon rejimlerinden \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp. spondilodiskiti olan hastalarda tedavi rejimlerini kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n meta-analizinde, 3\u2019l\u00fc antimikrobiyal kombinasyonlar\u0131n, 2\u2019li kombinasyonlardan daha ba\u015far\u0131l\u0131 oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella <\/i>spp. spondilodiskiti tedavisinde 3\u2019l\u00fc antimikrobiyal i\u00e7eren kombinasyon tedavisi \u00f6nerilir <i>(\u00c7ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, zay\u0131f \u00f6neri).<\/i><\/p>\n<h4 class=\"p2\">19- <i>Brucella<\/i> spp. spondilodiskiti tedavisinde kinolon i\u00e7eren tedavi rejimleri i\u00e7ermeyen rejimlere \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri: <\/strong><i>Brucella<\/i> spp. spondilodiskiti olan hastalarda kinolon i\u00e7eren antimikrobiyal kombinasyonlarla, i\u00e7ermeyen kombinasyonlar\u0131 kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n kan\u0131t d\u00fczeylerinin ve kalitesinin yetersiz oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella<\/i> spp. spondilodiskiti tedavisinde kinolon i\u00e7eren kombinasyonlar\u0131n kullan\u0131m\u0131 konusunda kan\u0131ta dayal\u0131 \u00f6neri yap\u0131labilmesi m\u00fcmk\u00fcn de\u011fildir. Bu konuda bilgi bo\u015flu\u011fu vard\u0131r. Rehberi haz\u0131rlayan uzmanlar taraf\u0131ndan, <i>Brucella<\/i> spp. spondilodiskiti olgular\u0131n\u0131n kombinasyon tedavisinde kinolonlar\u0131n, artan g\u00fcvenlik endi\u015feleri nedeniyle ilk se\u00e7enek olarak yer almamas\u0131, ilk se\u00e7enek ila\u00e7lar\u0131n (DOX, RIF, GEN, STREP) yan etki, ila\u00e7 etkile\u015fimi gibi herhangi bir nedenle kullan\u0131lamad\u0131\u011f\u0131 durumlarda d\u00fc\u015f\u00fcn\u00fclmesi \u00f6nerilmektedir (<i>Bilgi bo\u015flu\u011fu<\/i>).<\/p>\n<h4 class=\"p2\">20- <i>Brucella <\/i>spp. spondilodiskiti tedavisinde \u00fc\u00e7 aydan uzun s\u00fcreli tedavi \u00fc\u00e7 aydan k\u0131sa s\u00fcreli tedavilere \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp. spondilodiskiti olan hastalarda 3 aydan uzun s\u00fcren antimikrobiyal tedavi rejimlerini, 3 aydan k\u0131sa s\u00fcren tedavilerle kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n kan\u0131t d\u00fczeylerinin ve kalitesinin yetersiz oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella<\/i> spp. spondilodiskiti tedavisinin s\u00fcresinin ne kadar olmas\u0131 gerekti\u011fi konusunda kan\u0131ta dayal\u0131 \u00f6neri yap\u0131labilmesi m\u00fcmk\u00fcn de\u011fildir, bu konuda bilgi bo\u015flu\u011fu vard\u0131r. Rehberi haz\u0131rlayan uzmanlar taraf\u0131ndan, <i>Brucella<\/i> spp. spondilodiskiti tedavisinin en az 3 ay uygulanmas\u0131, tedavi sonunda klinik ve radyolojik olarak hasta baz\u0131nda de\u011ferlendirme yap\u0131larak gerekmesi halinde s\u00fcrenin uzat\u0131lmas\u0131 \u00f6nerilmektedir (<i>Bilgi bo\u015flu\u011fu<\/i>).<\/p>\n<h2 class=\"p1\">AMA\u00c7 VE KAPSAM<\/h2>\n<p class=\"p3\">Bruselloz hem \u00fclkemizde hem de d\u00fcnyan\u0131n pek \u00e7ok b\u00f6lgesinde yayg\u0131n olarak g\u00f6r\u00fclmeye devam eden zoonotik bir hastal\u0131k olmas\u0131na kar\u015f\u0131n genel olarak ihmal edilmi\u015ftir. D\u00fcnyada y\u0131ll\u0131k 150-250 bin aras\u0131nda insan brusellozu olgusu bildirilmekle birlikte, \u00f6zellikle d\u00fc\u015f\u00fck gelirli \u00fclkelerde bruselloz s\u0131kl\u0131\u011f\u0131 konusunda g\u00fcvenilir veriler bulunmamaktad\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>Hastal\u0131k \u00fclkemizde halen endemiktir ve \u00e7ok say\u0131da insan\u0131 etkilemektedir.<span class=\"Apple-converted-space\">\u00a0 <\/span>Hastal\u0131\u011f\u0131n tan\u0131 ve tedavisi genellikle ki\u015fisel\/b\u00f6lgesel tecr\u00fcbeler, k\u00fc\u00e7\u00fck \u00e7apl\u0131 kar\u015f\u0131la\u015ft\u0131rmal\u0131 klinik ara\u015ft\u0131rmalar ve olgu serilerinden elde edilen deneyimlerle y\u00f6nlendirilmektedir. Bruselloz tan\u0131 ve tedavisini y\u00f6nlendirmede kullan\u0131labilecek kan\u0131ta dayal\u0131 herhangi bir rehber bulunmad\u0131\u011f\u0131 i\u00e7in, brusellozun tan\u0131 ve tedavisinde kan\u0131ta dayal\u0131 \u00f6neriler sunmak \u00fczere bu rehber haz\u0131rlanm\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0 \u00a0<\/span><\/p>\n<p class=\"p3\">Rehber, T\u00fcrk Klinik Mikrobiyoloji ve \u0130nfeksiyon Hastal\u0131klar\u0131 (KL\u0130M\u0130K) Derne\u011fi\u2019nin \u00fcyeleri ve y\u00f6netiminin katk\u0131lar\u0131yla haz\u0131rlanm\u0131\u015f olup brusellozun tan\u0131 ve tedavisini kapsamaktad\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>Rehberin hedef grubunu gerek \u00fclkemizde, gerekse d\u00fcnyada bruselloz hastalar\u0131n\u0131 g\u00f6r\u00fcp, tan\u0131 ve tedavilerini y\u00f6nlendiren aile hekimleri ve ba\u015fta infeksiyon hastal\u0131klar\u0131 ve klinik mikrobiyoloji, i\u00e7 hastal\u0131klar\u0131, n\u00f6roloji, kardiyoloji, romatoloji olmak \u00fczere t\u00fcm uzmanl\u0131k alanlar\u0131ndan hekimler olu\u015fturmaktad\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h2 class=\"p1\">REHBER HAZIRLAMA BASAMAKLARI VE Y\u00d6NTEMLER\u0130 <span class=\"Apple-converted-space\">\u00a0<\/span><\/h2>\n<p class=\"p3\">Rehberin haz\u0131rlanmas\u0131nda ABD \u0130nfeksiyon Hastal\u0131klar\u0131 Derne\u011fi\u2019nin (IDSA) Klinik Uygulama K\u0131lavuzlar\u0131n\u0131n Geli\u015ftirilmesi Rehberi (1) \u00f6nerileri esas al\u0131nm\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h3 class=\"p7\"><span class=\"s3\"><b><br \/>\n<\/b>Rehber Haz\u0131rlama Grubunun ve G\u00f6revlerinin Belirlenmesi<\/span><\/h3>\n<p class=\"p3\">Dernek Y\u00f6netim Kurulu, KL\u0130M\u0130K Derne\u011fi\u2019nin rehber haz\u0131rlama \u00e7a\u011fr\u0131s\u0131na olumlu yan\u0131t veren, bruselloz konusunda yay\u0131n\u0131 bulunan ve \u201csistematik derleme ve meta-analizi yapma\u201d konusunda e\u011fitim ald\u0131\u011f\u0131n\u0131 kan\u0131tlayan 12 infeksiyon hastal\u0131klar\u0131 ve klinik kikrobiyoloji uzman\u0131n\u0131 rehberi haz\u0131rlamak \u00fczere se\u00e7mi\u015ftir. D\u00fczenli yap\u0131lan haftal\u0131k toplant\u0131lar\u0131n \u00fc\u00e7\u00fcnc\u00fcs\u00fcnden sonra istatistiksel analizler ve GRADE sistemi kapsam\u0131nda ortaya \u00e7\u0131kan destek ihtiyac\u0131 nedeniyle bir biyoistatistik uzman\u0131 (CA) da gruba dahil edilmi\u015ftir. Rehber Haz\u0131rlama Grubu\u2019na se\u00e7ilen \u00fcyelerden bir grup (AB, S\u00d6, FK, SB, ETY, EMS) literat\u00fcr\u00fc sistematik olarak taram\u0131\u015f, uygun makaleleri belirlemi\u015f ve PICO [hasta\/pop\u00fclasyon (P), m\u00fcdahale\/indikator (I), kar\u015f\u0131la\u015ft\u0131rma\/kontrol (C), sonu\u00e7 (O)] format\u0131ndaki sorular\u0131 kullanarak bilimsel kan\u0131tlar\u0131 \u00f6zetlemi\u015ftir.<\/p>\n<h3 class=\"p3\"><b><\/b>\u00c7\u0131kar \u00c7at\u0131\u015fmas\u0131 Bildirimleri<\/h3>\n<p class=\"p8\"><span class=\"s4\">Rehber Grubu\u2019nda yer alan ki\u015filerin \u201cInternational Committee of Medical Journal Editors\u201d (ICMJE) taraf\u0131ndan olu\u015fturulmu\u015f formla (2) yapt\u0131klar\u0131 \u00e7\u0131kar \u00e7at\u0131\u015fmas\u0131 bildirimleri, KL\u0130M\u0130K Derne\u011fi 18. D\u00f6nem Etik Kurul\u2019u taraf\u0131ndan g\u00f6zden ge\u00e7irilmi\u015f, de\u011ferlendirilmi\u015f ve onaylanm\u0131\u015ft\u0131r. <\/span><span class=\"s3\">\u015eeffafl\u0131k sa\u011flamak i\u00e7in Etik Kurul, konuyla ilgili t\u00fcm ili\u015fkilerin tam olarak a\u00e7\u0131klanmas\u0131n\u0131 talep etmi\u015f ve R<\/span><span class=\"s4\">ehber Grubu\u2019nun t\u00fcm \u00fcyeleri, <\/span><span class=\"s3\">Etik Kurul\u2019un, k\u0131lavuz konusuyla ilgili ger\u00e7ek, potansiyel veya g\u00f6r\u00fcn\u00fcr bir \u00e7at\u0131\u015fma olu\u015fturdu\u011fu \u015feklinde yorumlanabilecek herhangi bir finansal, fikri veya di\u011fer \u00e7\u0131karlar\u0131n if\u015fa edilmesi talebine uymu\u015ftur. Etik Kurul taraf\u0131ndan a\u00e7\u0131klanan ili\u015fkilerin olas\u0131 \u00e7\u0131kar \u00e7at\u0131\u015fmas\u0131 a\u00e7\u0131s\u0131ndan de\u011ferlendirilmesi, mali ili\u015fkinin g\u00f6reli a\u011f\u0131rl\u0131\u011f\u0131na (parasal miktar) ve ili\u015fkinin alakas\u0131na (<\/span><span class=\"s4\">konuyla veya s\u00f6z konusu olan \u00f6neriyle ili\u015fkili olabilece\u011fi ba\u011f\u0131ms\u0131z bir g\u00f6zlemci taraf\u0131ndan kolayca de\u011ferlendirilebilen seviyesine)<\/span><span class=\"s3\"> dayand\u0131r\u0131lm\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>Ek olarak, Rehber Grubu\u2019nun t\u00fcm \u00fcyeleri, 2547 say\u0131l\u0131 Y\u00fcksek \u00d6\u011fretim Kanunu Madde 37\u2019de belirtilen kurallara da uymakla y\u00fck\u00fcml\u00fcd\u00fcr (3).<span class=\"Apple-converted-space\">\u00a0 <\/span><\/span><span class=\"s4\">\u00c7\u0131kar \u00e7at\u0131\u015fmas\u0131 olarak kabul edilen ve edilmeyen ili\u015fki t\u00fcrleri Ek Dok\u00fcmanlar\u0131n 4. maddesinde verilmi\u015ftir.<span class=\"Apple-converted-space\">\u00a0<\/span><\/span><\/p>\n<h3 class=\"p7\">PICO Sorular\u0131n\u0131n Olu\u015fturulmas\u0131<\/h3>\n<p class=\"p3\">\u00d6ncelikle Rehber Grubu\u2019nun t\u00fcm \u00fcyelerinden PICO format\u0131nda sorular haz\u0131rlamas\u0131 istenmi\u015ftir. Haz\u0131rlanan sorular, t\u00fcm \u00fcyeler taraf\u0131ndan \u00f6nem derecesine g\u00f6re puanlanarak en \u00e7ok puan\u0131 alan ve \u00fczerinde uzla\u015f\u0131lm\u0131\u015f olan toplam 20 soru se\u00e7ilmi\u015ftir. Her bir klinik sorunun yan\u0131tlanmas\u0131 i\u00e7in 2-4 \u00fcye g\u00f6revlendirilmi\u015ftir. Yay\u0131nlar\u0131n taranmas\u0131ndan sonra uygun yan\u0131tlar\u0131n verilemeyece\u011fi durumlar i\u00e7in sorularda de\u011fi\u015fiklik yap\u0131lm\u0131\u015ft\u0131r (5. ve 12. PICO sorular\u0131).<\/p>\n<h3 class=\"p7\">Sonlan\u0131mlar ve M\u00fcdahalelerin, De\u011ferlerin, Tercihlerin ve Olanaklar\u0131n De\u011ferlendirilmesi<span class=\"Apple-converted-space\">\u00a0<\/span><\/h3>\n<p class=\"p3\">De\u011ferlendirilmesi uygun bulunan t\u00fcm sonlan\u0131mlar \u00f6nceden belirlendi ve karar vermedeki \u00f6nemlerine g\u00f6re derecelendirildi. Her bir PICO sorusu i\u00e7in kullan\u0131lacak sonlan\u0131mlar\u0131n s\u0131ralanmas\u0131na grubun tamam\u0131n\u0131n uzla\u015f\u0131s\u0131yla karar verildi. Tan\u0131 testleri i\u00e7in \u201cduyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fck\u201d, tedavilerde \u201crelaps, tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, yan etki\u201d, ek olarak infektif endokarditle ilgili olanlarda \u201c\u00f6l\u00fcm\u201d, hastal\u0131\u011f\u0131n gebelerdeki y\u00f6netimi i\u00e7in \u201cgebelik komplikasyonlar\u0131\u201d sonlan\u0131m olarak belirlendi. \u00d6zg\u00fcl bir antibiyotik rejimini, di\u011fer bir rejimle kar\u015f\u0131la\u015ft\u0131ran ve ayn\u0131 etkinlik\/faydada bulunan PICO sorular\u0131 i\u00e7in, karar vermede \u201cistenmeyen etkiler\u201d sonlan\u0131m\u0131 kritik olarak s\u0131ralanabildi, ancak ak\u0131lc\u0131 kullan\u0131m, ula\u015f\u0131labilir olmas\u0131, hasta konforu ve maliyet gibi di\u011fer konular da de\u011ferlendirildi.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h3 class=\"p3\">Kan\u0131tlar\u0131n Ara\u015ft\u0131r\u0131lmas\u0131, Toplanmas\u0131 ve Hangi Kan\u0131tlar\u0131n Kullan\u0131laca\u011f\u0131n\u0131n Belirlenmesi<span class=\"Apple-converted-space\">\u00a0<\/span><\/h3>\n<p class=\"p3\">Literat\u00fcr taramas\u0131n\u0131 yapan ekip (AB, S\u00d6, FK, SB, ETY, EMS) \u00e7al\u0131\u015fmalar\u0131n\u0131 klinik sorular\u0131 yan\u0131tlayabilecek \u015fekilde y\u00fcr\u00fctt\u00fc.<b> <\/b>ULAKB\u0130M TR Dizin, PubMed ve Cochrane elektronik veritabanlar\u0131nda dizinlenmi\u015f T\u00fcrk\u00e7e ve \u0130ngilizce dillerindeki \u226517 ya\u015f hastalar\u0131 i\u00e7eren yay\u0131nlar y\u0131l s\u0131n\u0131r\u0131 olmaks\u0131z\u0131n tarand\u0131. \u0130lk tarama 2 Mart 2022 tarihinde yap\u0131ld\u0131 ve ard\u0131ndan 15-30 Haziran 2022 tarihinde tekrarland\u0131. Taramalar\u0131 yapanlar elde ettikleri makalelerin ba\u015fl\u0131k ve \u00f6zetlerini okuduktan sonra \u00f6zg\u00fcl pop\u00fclasyon, dahil edilme ve hari\u00e7 tutulma \u00f6l\u00e7\u00fctlerine g\u00f6re uygun bulduklar\u0131n\u0131n tam metnini incelediler. Tam metin incelemelerinde, her bir PICO sorusundaki pop\u00fclasyona, m\u00fcdahaleye, kar\u015f\u0131la\u015ft\u0131rma grubuna, sonlan\u0131ma dair veri i\u00e7erenlerin dahil olmas\u0131 sa\u011flanacak \u015fekilde \u00f6nceden haz\u0131rlanm\u0131\u015f dahil edilme ve hari\u00e7 tutulma \u00f6l\u00e7\u00fctlerine g\u00f6re uygun bulunanlardan elde edilen veriler haz\u0131rlanm\u0131\u015f formlara kaydedildi. Literat\u00fcr taramalar\u0131ndan elde edilmi\u015f makaleler, t\u00fcm grup taraf\u0131ndan dikkatle de\u011ferlendirildi ve hangi \u00e7al\u0131\u015fmalar\u0131n son analize dahil edilece\u011fine karar verildi. Kar\u015f\u0131la\u015ft\u0131rmal\u0131 klinik ara\u015ft\u0131rmalar\u0131n olmas\u0131 halinde \u00e7al\u0131\u015fmalar\u0131n PICO sorular\u0131na yan\u0131t olu\u015fturabilecek \u015fekilde meta-analizleri yap\u0131ld\u0131.<span class=\"Apple-converted-space\">\u00a0 <\/span>Kar\u015f\u0131la\u015ft\u0131rmal\u0131 \u00e7al\u0131\u015fma bulunamayan infektif endokardit, n\u00f6robruselloz ve gebelik i\u00e7in, tek olgu sunumlar\u0131 ve olgu serilerinden, PICO sorular\u0131na yan\u0131t i\u00e7erenlerin verileri \u00f6nceden haz\u0131rlanm\u0131\u015f formlara kaydedilerek, sistematik derleme ve IPD meta-analizleri yap\u0131ld\u0131. <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h3 class=\"p3\">Rehberde ve Yay\u0131n Taramalar\u0131nda Kabul Edilen Tan\u0131mlamalar<\/h3>\n<p class=\"p3\"><em><strong>Akut Bruselloz: <\/strong><\/em>Bir y\u0131ldan daha k\u0131sa s\u00fcredir<b><i> <\/i><\/b>devam eden ate\u015f, yorgunluk, i\u015ftahs\u0131zl\u0131k, kilo kayb\u0131, ba\u015f a\u011fr\u0131s\u0131, gece terlemesi, yayg\u0131n kas ve eklem a\u011fr\u0131lar\u0131 olan hastada;<\/p>\n<ul>\n<li class=\"p9\">Kan, v\u00fccut s\u0131v\u0131lar\u0131 (idrar, BOS, sinovyal s\u0131v\u0131 ve plevral s\u0131v\u0131 vb.) veya dokudan (kemik ili\u011fi, karaci\u011fer biyopsisi vb) bakterinin \u00fcretilmesi,<span class=\"Apple-converted-space\">\u00a0<\/span><\/li>\n<li class=\"p10\">Standart t\u00fcp agl\u00fctinasyon testinde <i>Brucella<\/i> total antikor titresinin \u22651:160 pozitif olmas\u0131,<\/li>\n<li class=\"p10\">\u22652 hafta arayla al\u0131nm\u0131\u015f akut ve konvalesan serum \u00f6rneklerinde <i>Brucella<\/i> antikor titresinde 4 kat veya daha fazla art\u0131\u015f olmas\u0131 (\u00fcstteki laboratuvar kriterini kar\u015f\u0131lamayan hastalarda).<\/li>\n<\/ul>\n<p class=\"p3\"><strong><em>Relaps Bruselloz:<\/em> <\/strong>Akut bruselloz tedavisi tamamland\u0131ktan ve iyile\u015fme g\u00f6zlendikten sonra brusellozla uyumlu objektif semptom ve bulgular\u0131n yeniden ortaya \u00e7\u0131kmas\u0131d\u0131r;<\/p>\n<ul>\n<li class=\"p11\">Yeniden k\u00fclt\u00fcr pozitifle\u015fmesi veya<\/li>\n<li class=\"p10\">Antikor titrelerinde art\u0131\u015f olmal\u0131d\u0131r.<\/li>\n<\/ul>\n<p class=\"p3\"><strong><em>Kronik Bruselloz:<\/em><\/strong>On iki aydan daha uzun s\u00fcredir brusellozla uyumlu semptom veya bulgular\u0131n olmas\u0131 ve yukar\u0131da tan\u0131mlanm\u0131\u015f \u201cakut bruselloz\u201d \u00f6l\u00e7\u00fctlerinin kar\u015f\u0131lanmas\u0131;<\/p>\n<ul>\n<li class=\"p10\">Fokal infeksiyon (tek bir organ veya organ sistemiyle ili\u015fkili semptomlar\u0131n belirgin olmas\u0131) veya<\/li>\n<li class=\"p10\">Relaps bruselloz \u015feklinde g\u00f6r\u00fclebilir<\/li>\n<\/ul>\n<p class=\"p3\"><strong><em>Uzam\u0131\u015f Konvalesan: <\/em><\/strong>Bruselloz tan\u0131s\u0131yla bir tedavi k\u00fcr\u00fcn\u00fc tamamlam\u0131\u015f ve antikor titreleri d\u00fc\u015fm\u00fc\u015f, hatta kaybolmu\u015f bir hastada, ate\u015f gibi objektif bulgular\u0131 olmaks\u0131z\u0131n infeksiyonun baz\u0131 semptomlar\u0131n\u0131n devam etmesidir. <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong><em>Komplike Olmam\u0131\u015f Bruselloz:<\/em><\/strong><i> <\/i>Fokal tutulumun olmad\u0131\u011f\u0131 hastal\u0131k.<\/p>\n<p class=\"p3\"><strong><em>Komplike Bruselloz:<\/em><\/strong> Fokal tutulumlar\u0131n [kemik, eklem, genitor\u00fcriner, kardiyak, merkezi sinir sistemi (MSS), vb.] oldu\u011fu hastal\u0131k.<\/p>\n<h3 class=\"p7\">Kan\u0131tlar\u0131n \u00d6zetlenmesi, Kan\u0131tlar\u0131n G\u00fcc\u00fcn\u00fcn Derecelendirilmesi ve \u00d6nerilerin Olu\u015fturulmas\u0131<\/h3>\n<p class=\"p3\">Se\u00e7ilen makaleler i\u00e7in kalitatif veya kantitatif analizlerden hangisinin yap\u0131laca\u011f\u0131na t\u00fcm grup birlikte karar verdi. Her PICO sorusu i\u00e7in kan\u0131tlar\u0131n \u00f6zeti tablosu literat\u00fcr tarama ekibi taraf\u0131ndan haz\u0131rland\u0131.<span class=\"Apple-converted-space\">\u00a0 <\/span>Randomize kontroll\u00fc \u00e7al\u0131\u015fmalar\u0131n, non-randomize kar\u015f\u0131la\u015ft\u0131rmal\u0131 \u00e7al\u0131\u015fmalar\u0131n, tan\u0131 testi \u00e7al\u0131\u015fmalar\u0131n\u0131n ve olgu serilerinin yanl\u0131l\u0131k de\u011ferlendirmelerinde, her PICO sorusu ve her bir ayr\u0131 sonlan\u0131m i\u00e7in kan\u0131tlar\u0131n derecelendirilmesinde ve \u00f6nerilerin g\u00fcc\u00fcn\u00fcn belirlenmesinde \u201cGrading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group\u201d \u00f6nerileri kullan\u0131ld\u0131 (4-8).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Her bir PICO sorusu i\u00e7in haz\u0131rlanm\u0131\u015f kan\u0131tlar\u0131n \u00f6zeti tablosu, t\u00fcm rehber grubu \u00fcyeleri taraf\u0131ndan dikkatle incelendi ve uygun \u015fekilde d\u00fczenlendi. Bu incelemeler tamamlanarak haz\u0131rlanan son kan\u0131t \u00f6zetleri, t\u00fcm gruba sunularak tart\u0131\u015f\u0131ld\u0131ktan sonra \u00f6neriler yap\u0131ld\u0131. Literat\u00fcr tarama y\u00f6ntemlerine, tarama sonu\u00e7lar\u0131n\u0131 detayland\u0131ran PRISMA ak\u0131\u015f \u015femalar\u0131na, veri bilgi formlar\u0131na, kan\u0131tlar\u0131n \u00f6zet tablolar\u0131na ve meta-analizi sonu\u00e7lar\u0131na ek d\u00f6k\u00fcmanlar k\u0131sm\u0131ndan ula\u015f\u0131labilir.<\/p>\n<div id=\"attachment_26964\" style=\"width: 2196px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S1.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-26964\" class=\"wp-image-26964 size-full\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S1.png\" alt=\"\" width=\"2186\" height=\"1784\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S1.png 2186w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S1-319x260.png 319w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S1-662x540.png 662w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S1-768x627.png 768w\" sizes=\"auto, (max-width: 2186px) 100vw, 2186px\" \/><\/a><p id=\"caption-attachment-26964\" class=\"wp-caption-text\"><strong>\u015eekil 1.<\/strong> GRADE Y\u00f6ntemiyle Kan\u0131tlar\u0131n Kalitesini ve \u00d6nerilerin G\u00fcc\u00fcn\u00fc Derecelendirme Yakla\u015f\u0131m\u0131 ve Anlamlar\u0131 (1, 4)<\/p><\/div>\n<p class=\"p3\"><span class=\"s2\">\u00d6neriler, GRADE yakla\u015f\u0131m\u0131yla uyumlu olacak \u015fekilde \u201cg\u00fc\u00e7l\u00fc\u201d veya \u201czay\u0131f\u201d olarak s\u0131n\u0131fland\u0131r\u0131lm\u0131\u015f olup \u201c\u00f6nerilir\u201d ifadesi g\u00fc\u00e7l\u00fc \u00f6neriyi, \u201cd\u00fc\u015f\u00fcn\u00fclebilir\u201d ifadesi zay\u0131f \u00f6neriyi yans\u0131tmaktad\u0131r. Sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131 ve sa\u011fl\u0131k politikas\u0131 yap\u0131c\u0131lar\u0131 i\u00e7in g\u00fc\u00e7l\u00fc ve zay\u0131f \u00f6nerilerin ne anlama geldi\u011fi \u015eekil 1\u2019de a\u00e7\u0131kland\u0131.<span class=\"Apple-converted-space\">\u00a0<\/span><\/span><\/p>\n<p class=\"p3\">Bir\u00e7ok \u00f6neri i\u00e7in y\u00fcksek kalitede kan\u0131t yoktu.<span class=\"Apple-converted-space\">\u00a0 <\/span>Kan\u0131t kalite seviyesi d\u00fc\u015f\u00fck olmas\u0131na kar\u015f\u0131n g\u00fc\u00e7l\u00fc \u00f6neri sadece, rehber grubu \u00fcyelerinin, \u00f6nerinin bir veya daha fazla paradigmaya uygun oldu\u011funu d\u00fc\u015f\u00fcnmeleri durumunda yap\u0131ld\u0131. Bu t\u00fcr \u00f6nerilerde, GRADE\u2019de de \u00f6nerilen a\u015fa\u011f\u0131daki iki paradigma dikkate al\u0131nd\u0131:<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<ol>\n<li class=\"p12\">Hayat\u0131 tehdit eden bir durum i\u00e7in d\u00fc\u015f\u00fck kaliteli kan\u0131tlarla yarar\u0131n g\u00f6sterilmesi (zarara dair kan\u0131tlar\u0131n d\u00fc\u015f\u00fck veya y\u00fcksek olmas\u0131yla birlikte),<\/li>\n<li class=\"p12\">D\u00fc\u015f\u00fck kaliteli kan\u0131tlarla yarar g\u00f6sterilirken, y\u00fcksek kaliteli kan\u0131tlarla zarar olmad\u0131\u011f\u0131n\u0131n g\u00f6sterilmesi.<span class=\"Apple-converted-space\">\u00a0<\/span><\/li>\n<\/ol>\n<p class=\"p3\">\u0130yi klinik uygulamalar ile ilgili \u00f6neriler i\u00e7in de GRADE y\u00f6ntemleri kullan\u0131ld\u0131. \u0130yi bir klinik uygulama, rehber grubu taraf\u0131ndan sa\u011fl\u0131k bak\u0131m\u0131 uygulamas\u0131 i\u00e7in zorunlu kabul edilen, \u00f6zetlenmesi g\u00fc\u00e7 olan \u00e7ok say\u0131da dolayl\u0131 kan\u0131tla desteklenen ve bu \u00f6nerinin uygulanmas\u0131n\u0131n b\u00fcy\u00fck, net bir pozitif sonuca yol a\u00e7aca\u011f\u0131n\u0131 i\u015faret eden bir mesaj\u0131 temsil eder.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">\u201cBilgi bo\u015flu\u011fu\u201d, klinik \u00f6neri yapabilmek i\u00e7in \u00f6nemli ara\u015ft\u0131rma gereksiniminin oldu\u011fu durumlarda kullan\u0131ld\u0131.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">T\u00fcm grup \u00fcyeleri, dokuz ay boyunca her \u00e7ar\u015famba g\u00fcn\u00fc Zoom platformu \u00fczerinden yap\u0131lan toplant\u0131larda bir araya gelerek kan\u0131t \u00f6zetlerini sundular ve \u00f6nerileri geli\u015ftirdiler. \u00dcyeler rehberin haz\u0131rlanmas\u0131na e\u015fit oranda katk\u0131 verdi ve \u00f6nerileri onaylad\u0131.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h3 class=\"p7\"><b><br \/>\n<\/b>Rehberin Yaz\u0131lmas\u0131<\/h3>\n<p class=\"p3\">Rehber tasla\u011f\u0131 grup \u00fcyeleri taraf\u0131ndan olu\u015fturularak, Microsoft word dosyas\u0131 halinde Google Drive\u2019a y\u00fcklendi. Her bir PICO sorusu i\u00e7in, ilgili ki\u015filer taraf\u0131ndan toplant\u0131larda elde edilmi\u015f uzla\u015f\u0131 \u00f6nerileri ve kan\u0131tlar\u0131n \u00f6zeti bu tasla\u011fa eklendi. T\u00fcm grup \u00fcyeleri taslak metni okuyarak uygun buldu\u011fu d\u00fczenlemeleri yapt\u0131.<\/p>\n<h3 class=\"p7\">Rehberin Revizyonu<span class=\"Apple-converted-space\">\u00a0<\/span><\/h3>\n<p class=\"p3\"><span class=\"s2\">Mevcut literat\u00fcr g\u00f6zden ge\u00e7irilerek, \u00f6nerilere etki edebilecek yeni veri olup olmad\u0131\u011f\u0131 kontrol edilecektir. Yeni veri olmas\u0131 halinde rehber grubu bir araya gelerek olas\u0131 de\u011fi\u015fiklikleri tart\u0131\u015facak ve yeni \u00f6nerilerde bulunacakt\u0131r. <span class=\"Apple-converted-space\">\u00a0<\/span><\/span><\/p>\n<h2 class=\"p1\">GENEL B\u0130LG\u0130LER<\/h2>\n<p class=\"p3\"><span class=\"s2\"><i>Brucella<\/i> cinsi bakterilerin neden oldu\u011fu bruselloz, esas olarak bir \u00e7iftlik hayvan\u0131 hastal\u0131\u011f\u0131d\u0131r, insanlar kazara konak olur. \u0130lk kez 1859\u2019da Malta\u2019da, \u0130ngiliz birliklerindeki askerler aras\u0131nda y\u00fcksek ate\u015fle giden bir hastal\u0131\u011f\u0131n ortaya \u00e7\u0131kmas\u0131 \u00fczerine David Bruce ve arkada\u015flar\u0131n\u0131n yapt\u0131\u011f\u0131 ara\u015ft\u0131rma s\u0131ras\u0131nda tan\u0131nm\u0131\u015f, etken bakteri ise ayn\u0131 ara\u015ft\u0131rmac\u0131lar taraf\u0131ndan 1887 y\u0131l\u0131nda izole edilmi\u015ftir. Almroth Wright taraf\u0131ndan Widal testinin bu hastal\u0131\u011fa uyarlanmas\u0131yla 1897 y\u0131l\u0131nda bruselloz tan\u0131s\u0131nda agl\u00fctinasyon testlerinin kullan\u0131m\u0131na ba\u015flanm\u0131\u015ft\u0131r (9). Ond\u00fclan ate\u015f, Akdeniz ate\u015fi veya Malta ate\u015fi diye de adland\u0131r\u0131labilen insan brusellozu, hayvan brusellozunun ortadan kald\u0131r\u0131lmas\u0131yla geli\u015fmi\u015f \u00fclkelerde elimine edilmi\u015ftir.<span class=\"Apple-converted-space\">\u00a0 <\/span>Buna kar\u015f\u0131l\u0131k geli\u015fmekte olan \u00fclkelerde hayvan brusellozunun devam etmesinin do\u011fal bir sonucu olarak halen endemik \u015fekilde g\u00f6r\u00fclen bir zoonozdur. \u0130nsanlarda s\u0131kl\u0131kla akut ate\u015fli bir hastal\u0131k olarak ortaya \u00e7\u0131kar, ancak persiste ederek kronik, \u00e7ok \u00e7e\u015fitli komplikasyonlar\u0131 olan bir hastal\u0131k \u015feklinde de seyredebilir. <i>Brucella<\/i> spp. do\u011fal kona\u011f\u0131 olan hayvanlarda hafif veya asemptomatik infeksiyonlara yol a\u00e7ar, glukoza tercih etti\u011fi bir \u015feker olan eritritolden zengin organlarda yerle\u015fmeyi tercih eder. Hayvanlardaki meme, uterus, plasenta ve epididim gibi organlar eritritolden zengindir; b\u00f6ylece bakteri hayvanlarda bu dokulara yerle\u015ferek d\u00fc\u015f\u00fc\u011fe, infertiliteye veya hayat boyu s\u00fcrecek ta\u015f\u0131y\u0131c\u0131l\u0131\u011fa yol a\u00e7abilir. <i>Brucella<\/i> spp., infekte hayvanlar\u0131n s\u00fct\u00fcnde, idrar\u0131nda ve do\u011fum salg\u0131lar\u0131nda bol miktarda bulunur. \u0130nsan plasentas\u0131nda eritritol bulunmaz ancak bruselloz olmu\u015f gebelerde gebelik komplikasyonlar\u0131n\u0131n artt\u0131\u011f\u0131 da g\u00f6sterilmi\u015ftir (10,11).<span class=\"Apple-converted-space\">\u00a0<\/span><\/span><\/p>\n<h3 class=\"p7\">Etken<\/h3>\n<p class=\"p3\">Brusellozun etkeni Gram-negatif kokobasil g\u00f6r\u00fcn\u00fcml\u00fc, fak\u00fcltatif intrasell\u00fcler mikroorganizmalar olan <i>Brucella<\/i> cinsi bakterilerdir. <i>Brucella<\/i> spp.\u2019nin molek\u00fcler \u00e7al\u0131\u015fmalar\u0131, su\u015flar\u0131n genetik yap\u0131lar\u0131n\u0131n \u00e7ok benzer oldu\u011funu, asl\u0131nda tek t\u00fcr \u015feklinde de\u011ferlendirebilece\u011fini ve \u00f6nceden tan\u0131mlanm\u0131\u015f t\u00fcrlerin varyant olarak kabul edilebilece\u011fini g\u00f6stermi\u015ftir. Ancak klinik pratikte bu yakla\u015f\u0131m tatmin edici bulunmam\u0131\u015f ve sekizi kara, d\u00f6rd\u00fc ise deniz memelerinde hastal\u0131k yapan 12 t\u00fcr tan\u0131mlanm\u0131\u015ft\u0131r. \u0130nsanlarda hastal\u0131k yapan d\u00f6rt t\u00fcr <i>Brucella<\/i> <i>abortus<\/i>, <i>Brucella<\/i> melitensis, <i>Brucella<\/i> <i>suis<\/i> ve <i>Brucella<\/i> <i>canis<\/i>\u2019tir. <i>B. abortus<\/i>, s\u0131\u011f\u0131rlarda ve Amerikan bizonlar\u0131nda, <i>B. suis <\/i>domuzlarda ve Ren geyiklerinde, <i>B. melitensis<\/i> ise ke\u00e7i ve koyunlarda hastal\u0131k yapar. Bu 3 t\u00fcr insanda klasik bruselloza neden olur. \u00dclkemizde en yayg\u0131n olarak g\u00f6r\u00fclen t\u00fcr <i>B. melitensis<\/i>\u2019tir. <i>B. abortus<\/i>, <i>B. melitensis, B. suis<\/i>\u2019in fenotipik ve antijenik \u00f6zelliklerine g\u00f6re s\u0131ras\u0131yla yedi, \u00fc\u00e7 ve be\u015f biyovar\u0131 bulunmaktad\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span><i>B. canis<\/i> k\u00f6pek, tilki ve \u00e7akallar\u0131 infekte eder, insanda hafif hastal\u0131k yapt\u0131\u011f\u0131 bildirilmi\u015ftir. <i>Brucella<\/i> <i>delphini<\/i>, <i>Brucella<\/i> <i>pinnipediae <\/i>ve <i>Brucella<\/i> <i>cetaceae<\/i> deniz memelilerinde hastal\u0131k tablolar\u0131na neden olur. <i>B. abortus<\/i> ve <i>B. canis<\/i> nadir s\u00fcp\u00fcratif komplikasyonlarla daha hafif seyirli bir hastal\u0131k yaparken, <i>B. suis<\/i> destr\u00fcktif lezyonlara ve uzun s\u00fcren bir hastal\u0131\u011fa yol a\u00e7ar. <i>B. melitensis<\/i> de fagositik h\u00fccrelerde daha yo\u011fun konsantrasyonlarda \u00e7o\u011falabilmesi nedeniyle daha ciddi hastal\u0131\u011fa ve komplikasyonlara yol a\u00e7ar (10-12).<\/p>\n<div id=\"attachment_26971\" style=\"width: 2196px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S2.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-26971\" class=\"wp-image-26971 size-full\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S2.png\" alt=\"\" width=\"2186\" height=\"2021\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S2.png 2186w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S2-281x260.png 281w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S2-584x540.png 584w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S2-768x710.png 768w\" sizes=\"auto, (max-width: 2186px) 100vw, 2186px\" \/><\/a><p id=\"caption-attachment-26971\" class=\"wp-caption-text\"><strong>\u015eekil 2.<\/strong> Olas\u0131 <i>Brucella <\/i>spp. Tan\u0131mlanmas\u0131 \u0130\u00e7in Ak\u0131\u015f \u015eemas\u0131 (12)<\/p><\/div>\n<p class=\"p3\"><i>Brucella<\/i> t\u00fcrleri, k\u00fc\u00e7\u00fck (0.5\u00d70.6-1.5 \u03bcm), hareketsiz, kaps\u00fcls\u00fczd\u00fcr. K\u00fclt\u00fcrde, kompleks besiyerlerinde bir hafta kadar bir s\u00fcrede yava\u015f \u00fcrerler, baz\u0131lar\u0131 zorunlu aeroptur. <i>B. abortus<\/i> ve <i>B. suis<\/i> ise kapnofilik olup \u00fcreme i\u00e7in %5-10 karbondioksit gerektirirler. Karbonhidratlar\u0131 fermente etmezler. \u015eekil 2\u2019de olas\u0131 <i>Brucella<\/i> spp. tan\u0131mlamas\u0131nda kullan\u0131labilecek ak\u0131\u015f \u015femas\u0131 verilmi\u015ftir. Ekzotoksini olmayan <i>Brucella<\/i> t\u00fcrlerinin endotoksini de di\u011fer Gram-negatif \u00e7omaklar\u0131nkinden daha az toksiktir.<i> Brucella<\/i> t\u00fcrleri h\u00fccre duvar\u0131ndaki lipopolisakkarid (LPS)\u2019in O antijeni i\u00e7erip i\u00e7ermemesine g\u00f6re p\u00fcrt\u00fcks\u00fcz (\u201csmooth\u201d, translusen, homojen) veya p\u00fcrt\u00fckl\u00fc (\u201crough\u201d, opak, gran\u00fcler veya yap\u0131\u015fkan) bir \u015fekil alabilirler.<span class=\"Apple-converted-space\">\u00a0 <\/span>P\u00fcrt\u00fckl\u00fc koloni morfolojisinde bakterilerin virulans\u0131n\u0131n b\u00fcy\u00fck oranda azalmas\u0131, p\u00fcrt\u00fcks\u00fcz LPS O zincirinin virulans i\u00e7in \u00f6nemli bir fakt\u00f6r oldu\u011funu d\u00fc\u015f\u00fcnd\u00fcrmektedir.<span class=\"Apple-converted-space\">\u00a0 <\/span><i>Brucella<\/i> t\u00fcrleri retik\u00fcloendotelyal sistemde intrasell\u00fcler olarak da ya\u015fayabilir.<span class=\"Apple-converted-space\">\u00a0 <\/span>\u0130lk temastan sonr<span class=\"s5\">a <\/span>makrofaj ve monositler taraf\u0131ndan fagosite edilen bakteriler, bu h\u00fccreler i\u00e7inde ya\u015famaya ve \u00e7o\u011falmaya devam edebilir. Fagosite edilen bakteriler dalak, karaci\u011fer, kemik ili\u011fi, lenf nodlar\u0131 ve b\u00f6breklere ta\u015f\u0131n\u0131r. Bakteri, bu organlarda granulom formasyonunu ind\u00fckleyen proteinler salg\u0131lar (10-12).<\/p>\n<h3 class=\"p7\">D\u00fcnyada Brusellozun Epidemiyolojisi<\/h3>\n<div id=\"attachment_26973\" style=\"width: 2108px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S3.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-26973\" class=\"wp-image-26973 size-full\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S3.png\" alt=\"\" width=\"2098\" height=\"971\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S3.png 2098w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S3-390x181.png 390w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S3-810x375.png 810w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S3-768x355.png 768w\" sizes=\"auto, (max-width: 2098px) 100vw, 2098px\" \/><\/a><p id=\"caption-attachment-26973\" class=\"wp-caption-text\"><strong>\u015eekil 3.<\/strong> B\u00f6lgelere G\u00f6re D\u00fcnya Hayvan Sa\u011fl\u0131\u011f\u0131 Organizasyonu (WOAH\/OIE)\u2019na Bildirilmi\u015f Bruselloz Olgu Say\u0131lar\u0131 (2005\u20132019) (A) (Grafikteki her bir nokta, her bir y\u0131l i\u00e7inde bildirilen insan brusellozu olgular\u0131n\u0131n say\u0131s\u0131n\u0131, \u00e7ubuklarsa ortalama ve standart sapmay\u0131 g\u00f6stermektedir) ve y\u0131llar i\u00e7indeki seyri (B) (13)<\/p><\/div>\n<p class=\"p3\">Bruselloz hem insanlarda hem de \u00e7iftlik hayvanlar\u0131nda ciddi hastal\u0131klara neden olan, k\u00fcresel olarak g\u00f6r\u00fclen bir infeksiyon hastal\u0131\u011f\u0131d\u0131r. D\u00fcnyada y\u0131ll\u0131k olarak 150-250 bin aras\u0131nda insan brusellozu olgusu bildirilmesine ra\u011fmen, \u00f6zellikle d\u00fc\u015f\u00fck gelirli \u00fclkelerde bruselloz s\u0131kl\u0131\u011f\u0131 konusunda g\u00fcvenilir veriler bulunmamaktad\u0131r. K\u00fcresel insan brusellozu s\u0131kl\u0131\u011f\u0131n\u0131 belirlemek amac\u0131yla d\u00fcnyada mevcut raporlama sistemlerinde bulunan ulusal verileri bir araya getiren, k\u0131sa s\u00fcre \u00f6nce yay\u0131mlanm\u0131\u015f bir \u00e7al\u0131\u015fmada, s\u00f6z konusu verilerin y\u0131ll\u0131k k\u00fcresel s\u0131kl\u0131\u011f\u0131 belirlemek i\u00e7in olduk\u00e7a yetersiz oldu\u011fu, gereken raporlar\u0131n sadece %48\u2019inin girildi\u011fi, d\u00fcnya pop\u00fclasyonunun yakla\u015f\u0131k %47\u2019sinin bu raporlarda temsil edildi\u011fi g\u00f6r\u00fclm\u00fc\u015ft\u00fcr.<span class=\"Apple-converted-space\">\u00a0 <\/span>Ek olarak raporlarda temsil edilen pop\u00fclasyon ve ger\u00e7ek olgu say\u0131lar\u0131n\u0131n b\u00f6lgesel olarak b\u00fcy\u00fck farkl\u0131l\u0131klar g\u00f6sterdi\u011fi belirlenmi\u015f, t\u00fcm bu nedenlerle insan brusellozu s\u0131kl\u0131\u011f\u0131n\u0131n do\u011fru tahmin edilmesinin m\u00fcmk\u00fcn olmad\u0131\u011f\u0131 bildirilmi\u015ftir. Bu \u00e7al\u0131\u015fman\u0131n verileriyle haz\u0131rlanm\u0131\u015f, bildirimi yap\u0131lm\u0131\u015f olgu say\u0131lar\u0131n\u0131n b\u00f6lgesel da\u011f\u0131l\u0131m\u0131 ve y\u0131llar i\u00e7indeki seyri \u015eekil 3\u2019te verilmi\u015ftir (13).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<div id=\"attachment_26975\" style=\"width: 2963px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S4_V2.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-26975\" class=\"wp-image-26975 size-full\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S4_V2.png\" alt=\"\" width=\"2953\" height=\"2186\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S4_V2.png 2953w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S4_V2-351x260.png 351w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S4_V2-729x540.png 729w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S4_V2-768x569.png 768w\" sizes=\"auto, (max-width: 2953px) 100vw, 2953px\" \/><\/a><p id=\"caption-attachment-26975\" class=\"wp-caption-text\"><strong>\u015eekil 4.<\/strong> G\u00fcncel K\u00fcresel \u0130nsan Brusellozu S\u0131kl\u0131\u011f\u0131 (ula\u015f\u0131labilen en g\u00fcncel verilere g\u00f6re haz\u0131rlanm\u0131\u015ft\u0131r).<\/p><\/div>\n<p class=\"p3\">\u0130nsan brusellozu, Avrupa\u2019da genel olarak eradike edilmi\u015f olmas\u0131na ra\u011fmen Arnavutluk, Bosna-Hersek, Kuzey Makedonya, S\u0131rbistan, Kosova, Yunanistan, Portekiz ve \u0130talya\u2019da halen yerel insan brusellozu olgular\u0131 endemik olarak g\u00f6r\u00fclmektedir. Ancak \u00f6zellikle 2016 y\u0131l\u0131ndan itibaren olgu say\u0131lar\u0131nda belirgin azalma oldu\u011fu ifade edilmektedir. Avrupa Hastal\u0131k \u00d6nleme ve Kontrol Merkezi (ECDC) 2022 Raporu\u2019nda, Avrupa Birli\u011fi ve Avrupa Ekonomik Alan\u0131 (EU\/EEA)\u2019nda bruselloz insidans\u0131n\u0131n 0.03 olgu\/100 000 ki\u015fi oldu\u011fu, 2020 y\u0131l\u0131nda Yunanistan ve Portekiz\u2019in en y\u00fcksek yerel olgu say\u0131lar\u0131na sahip oldu\u011fu belirtilmektedir. En d\u00fc\u015f\u00fck olgu say\u0131s\u0131n\u0131n 2020\u2019de g\u00f6r\u00fclmesinde gerek hafif seyirli olgular\u0131n ba\u015fvurmamas\u0131na gerekse seyahatlerin azalmas\u0131na yol a\u00e7mas\u0131 nedeniyle COVID-19 pandemisinin etkili oldu\u011fu d\u00fc\u015f\u00fcn\u00fclmektedir (14,15). Asya\u2019da bruselloz ba\u015fta Yemen, Suriye, \u0130ran, Filistin ve Suudi Arabistan olmak \u00fczere halen \u00e7ok say\u0131da \u00fclkede endemik olarak g\u00f6r\u00fclen bir hastal\u0131kt\u0131r. Afrika\u2019da yeterli veri olmamakla birlikte \u00f6zellikle Kenya, Eritre ve Cezayir\u2019den \u00e7ok say\u0131da olgu bildirilmektedir. Kuzey Amerika\u2019da olgu say\u0131lar\u0131 olduk\u00e7a d\u00fc\u015f\u00fckt\u00fcr; G\u00fcney Amerika\u2019da ise Asya kadar \u00e7ok olmamakla birlikte Arjantin, Brezilya, Venezuela ve Ekvador\u2019da di\u011fer b\u00f6lgelere g\u00f6re daha s\u0131k tan\u0131mlanmaktad\u0131r. Son olarak Avustralya\u2019da da d\u00fc\u015f\u00fck s\u0131kl\u0131kta olmakla birlikte halen tan\u0131mlanan bir hastal\u0131kt\u0131r. Brusellozun s\u0131kl\u0131\u011f\u0131n\u0131 ara\u015ft\u0131ran g\u00fcncel \u00e7al\u0131\u015fmalardan (13-20) yararlanarak haz\u0131rlam\u0131\u015f oldu\u011fumuz harita (\u015eekil 4), Papas ve arkada\u015flar\u0131n\u0131n (19) 2006 y\u0131l\u0131nda yapm\u0131\u015f oldu\u011fu harita ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, ge\u00e7en 16 y\u0131lda b\u00fcy\u00fck bir de\u011fi\u015fiklik olmad\u0131\u011f\u0131 dikkati \u00e7ekmektedir. Bu nedenle <span class=\"s1\">Laine ve arkada\u015flar\u0131 (13) taraf\u0131ndan da <\/span>belirtildi\u011fi gibi insan brusellozunun D\u00fcnya Sa\u011fl\u0131k \u00d6rg\u00fct\u00fc (WHO) taraf\u0131ndan tekrar \u201cihmal edilen \u00f6ncelikli zoonotik hastal\u0131k\u201d olarak tan\u0131mlanmas\u0131n\u0131n, gerekli kaynaklar\u0131n ayr\u0131lmas\u0131n\u0131 sa\u011flayarak hastal\u0131\u011f\u0131n neden oldu\u011fu zarar\u0131 ve kontrol stratejilerini belirlemede olduk\u00e7a \u00f6nemli olaca\u011f\u0131 a\u00e7\u0131kt\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Avrupa Birli\u011fi 2020 Zoonozlar Raporu\u2019nda, \u00fcye \u00fclkeler aras\u0131nda resmen brusellozdan ar\u0131nm\u0131\u015f 20 \u00fclkede sadece alt\u0131 s\u0131\u011f\u0131r s\u00fcr\u00fcs\u00fcnde infeksiyon tan\u0131mlanm\u0131\u015f ve prevalans\u0131n \u00e7ok d\u00fc\u015f\u00fck (&lt;%0.001) oldu\u011fu bildirilmi\u015ftir (15). Bulgaristan, H\u0131rvatistan, Macaristan, \u0130talya, Portekiz ve \u0130spanya\u2019dan olu\u015fan di\u011fer \u00fclkelerde ise s\u0131\u011f\u0131r brusellozu belirgin d\u00fc\u015f\u00fc\u015f g\u00f6stermi\u015f, taranan 157 000 s\u00fcr\u00fcn\u00fcn 603 (%0.38)\u2019\u00fcnde tan\u0131mlanm\u0131\u015ft\u0131r. Koyun ve ke\u00e7i brusellozu, ar\u0131nm\u0131\u015f \u00fclkelerde de di\u011fer \u00fclkelerde de stabil bir seyir izlenmi\u015f olup di\u011fer grupta yer alan \u00fclkelerde taranan 160 000 s\u00fcr\u00fcn\u00fcn 349 (%0.22)\u2019unda pozitiflik saptanm\u0131\u015ft\u0131r (21).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h3 class=\"p7\">T\u00fcrkiye\u2019de Brusellozun Epidemiyolojisi<\/h3>\n<div id=\"attachment_26981\" style=\"width: 1456px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T1.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-26981\" class=\"size-full wp-image-26981\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T1.png\" alt=\"\" width=\"1446\" height=\"998\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T1.png 1446w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T1-377x260.png 377w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T1-782x540.png 782w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T1-768x530.png 768w\" sizes=\"auto, (max-width: 1446px) 100vw, 1446px\" \/><\/a><p id=\"caption-attachment-26981\" class=\"wp-caption-text\"><strong>Tablo 1.<\/strong> 2008-2019 Y\u0131llar\u0131 Aras\u0131nda \u00dclkemizde Bildirimi Yap\u0131lm\u0131\u015f Bruselloz Olgu ve \u00d6l\u00fcm Say\u0131lar\u0131 (13, 20)<\/p><\/div>\n<p class=\"p3\">Bruselloz \u00fclkemizde endemik bir hastal\u0131kt\u0131r (\u015eekil 4). En fazla G\u00fcneydo\u011fu Anadolu ve Do\u011fu Anadolu b\u00f6lgelerinde g\u00f6r\u00fclmektedir. Tablo 1\u2019de 2008 y\u0131l\u0131ndan 2019 y\u0131l\u0131na kadar \u00fclkemizde bildirilmi\u015f bruselloz olgu say\u0131lar\u0131 g\u00f6r\u00fclmektedir (13,20).<span class=\"Apple-converted-space\">\u00a0 <\/span>\u0130llere g\u00f6re olgular\u0131n da\u011f\u0131l\u0131m\u0131na bak\u0131ld\u0131\u011f\u0131nda hastal\u0131\u011f\u0131n Do\u011fu ve G\u00fcneydo\u011fu Anadolu b\u00f6lgelerinde daha fazla olmak \u00fczere t\u00fcm \u00fclkede endemik \u015fekilde g\u00f6r\u00fcld\u00fc\u011f\u00fc dikkat \u00e7ekmektedir.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Hayvan brusellozu konusunda \u00fclkemizde ula\u015f\u0131labilen son yay\u0131nda ortalama s\u00fcr\u00fc prevalans\u0131n\u0131n 2012 y\u0131l\u0131ndan itibaren kitlesel a\u015f\u0131lama programlar\u0131yla %12.3\u2019e d\u00fc\u015ft\u00fc\u011f\u00fc bildirilmi\u015ftir (21).<\/p>\n<p class=\"p3\">T\u00fcm veriler bir arada de\u011ferlendirildi\u011finde \u00fclkemizde insan brusellozu insidans\u0131n\u0131n, \u00f6zellikle 2012\u2019deki kitlesel hayvan a\u015f\u0131lamalar\u0131yla hayvan brusellozunun azalmas\u0131na ba\u011fl\u0131 olarak 2012\u2019den 2015 y\u0131l\u0131na kadar d\u00fc\u015f\u00fc\u015f<span class=\"Apple-converted-space\">\u00a0 <\/span>g\u00f6sterdi\u011fi ve en d\u00fc\u015f\u00fck seviye olan 5.30\/100 000 ki\u015fiye indi\u011fi ancak 2016 y\u0131l\u0131ndan itibaren, yine muhtemelen hayvanlarda hastal\u0131\u011f\u0131n kontrol\u00fcn\u00fcn yetersizli\u011finin bir sonucu olarak tekrar y\u00fckselmeye ba\u015flad\u0131\u011f\u0131 ve 2019\u2019da, 2012 \u00f6ncesi seviyelere ula\u015farak 12.32\/100 000 ki\u015fiye \u00e7\u0131kt\u0131\u011f\u0131 g\u00f6r\u00fclmektedir.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h3 class=\"p7\">Brusellozun Bula\u015fmas\u0131<span class=\"Apple-converted-space\">\u00a0<\/span><\/h3>\n<p class=\"p3\">Brusellozun bula\u015fmas\u0131, hemen her zaman hayvan kaynaklar\u0131yla direkt veya indirekt temasla olur; s\u0131\u011f\u0131r, koyun, ke\u00e7i ve domuzlar en \u00f6nemli kaynaklard\u0131r. Hastal\u0131k, infekte hayvan doku veya sekresyonlar\u0131n\u0131n (kan, idrar, vajinal sekresyon, aborte fetus ve \u00f6zellikle plasenta) konjunktivayla veya \u00e7izilmi\u015f, hasarlanm\u0131\u015f deriyle direkt temas\u0131yla, infekte hayvanlar\u0131n \u00e7i\u011f veya past\u00f6rize edilmemi\u015f veya kaynat\u0131lmam\u0131\u015f s\u00fct ve s\u00fct \u00fcr\u00fcnlerinin a\u011f\u0131zdan al\u0131nmas\u0131yla, infekte aerosollerin inhalasyonla al\u0131nmas\u0131yla ve \u00e7ift\u00e7ilerin, mezbaha \u00e7al\u0131\u015fanlar\u0131n\u0131n ve laboratuvar \u00e7al\u0131\u015fanlar\u0131n\u0131n mesleki olarak mikroorganizmayla temas\u0131 yoluyla edinilebilir (22,23). Etteki bakteri miktar\u0131n\u0131n az olmas\u0131 ve genel olarak etin pi\u015firilerek t\u00fcketilmesi nedeniyle infekte hayvan etleriyle bula\u015fma nadirdir. <i>Brucella<\/i> t\u00fcrleri ah\u0131rlarda, laboratuvarlarda ve mezbahalarda hava yoluyla da bula\u015fabilir. Hayvanlarda kullan\u0131lan canl\u0131 a\u015f\u0131n\u0131n yanl\u0131\u015fl\u0131kla insanlara inok\u00fcle edilmesiyle de bula\u015fmalar bildirilmektedir. RB-51 a\u015f\u0131s\u0131, subinhibit\u00f6r konsantrasyonda RIF i\u00e7eren besiyerinde yineleyen pasajlarla elde edilmi\u015f bir <i>B. abortus<\/i> su\u015fu i\u00e7erdi\u011finden, bu yolla infekte olan ki\u015fideki etkenin RIF\u2019e diren\u00e7li oldu\u011fu bilinmelidir. \u0130nsanlar aras\u0131nda bula\u015fma nadir olmakla birlikte cinsel yolla, intrauterin, emzirmeyle, organ nakli ve kan transf\u00fczyonuyla bula\u015fmalar bildirilmi\u015ftir. <i>Brucella<\/i> t\u00fcrleri \u00e7i\u011f s\u00fct i\u00e7inde 2-6 hafta, kremada 4\u00b0C\u2019de 6 hafta, dondurmada 30 g\u00fcn, taze peynirde 15-100 g\u00fcn ya\u015fayabilirken, s\u00fct\u00fcn past\u00f6rizasyonu veya kaynat\u0131lmas\u0131yla \u00f6l\u00fcr (24,25).<\/p>\n<h3 class=\"p7\">Brusellozun Klinik \u00d6zellikleri<\/h3>\n<p class=\"p3\">Hastal\u0131\u011f\u0131n ink\u00fcbasyon s\u00fcresi 2-4 haftad\u0131r (5 g\u00fcn-6 ay). Hastal\u0131k, semptomlar\u0131n s\u00fcresine g\u00f6re akut (semptom ve bulgular\u0131n bir y\u0131ldan daha k\u0131sa s\u00fcredir oldu\u011fu durum) veya kronik (semptom ve bulgular\u0131n bir y\u0131ldan daha uzun s\u00fcredir devam etti\u011fi durum) olarak grupland\u0131r\u0131l\u0131r. Baz\u0131 yay\u0131nlar, semptomlar\u0131 3 aydan k\u0131sa s\u00fcrenleri akut, 3 ay -1 y\u0131l aras\u0131nda devam edenleri subakut olarak s\u0131n\u0131fland\u0131rmaktad\u0131r. Akut semptomatik hastal\u0131k, hastalar\u0131n yakla\u015f\u0131k yar\u0131s\u0131nda geli\u015fir, yar\u0131s\u0131nda ise asemptomatik seyir s\u00f6z konusudur. Ate\u015f aral\u0131kl\u0131 olabilir; bu nedenle ond\u00fclan (dalgal\u0131) ate\u015f diye de adland\u0131r\u0131l\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>Semptomatik hastalarda; ate\u015f, titreme, ba\u015f a\u011fr\u0131s\u0131, myalji, artralji, a\u015f\u0131r\u0131 gece terlemeleri, yorgunluk, i\u015ftahs\u0131zl\u0131k, kilo kayb\u0131, depresyon ve e\u015flik eden lokalize infeksiyon varsa tutulan v\u00fccut b\u00f6lgesini ilgilendiren semptomlar g\u00f6r\u00fcl\u00fcr. Fizik muayenede hastalar\u0131n %10\u201320\u2019sinde lenfadenomegali, %20-30\u2019unda splenomegali belirlenir (24-27).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Kronik brusellozda ya primer infeksiyonun yinelemesi (%5-15) ya da lokalize bir infeksiyona ait semptom ve bulgular vard\u0131r; bir y\u0131ldan uzun s\u00fcren klinik bulgular ve infeksiyonun objektif kan\u0131tlar\u0131 (y\u00fcksek antikor titreleri ve\/veya kan veya dokudan <i>Brucella<\/i> spp. \u00fcretilmesi) s\u00f6z konusudur. Akut bruselloz s\u0131ras\u0131nda da ortaya \u00e7\u0131kabilen lokalize infeksiyonlarda, en s\u0131k sakroiliit, spondilit veya artrit \u015feklinde seyreden osteoartik\u00fcler (%2), epididimoor\u015fit (%6) \u015feklinde seyreden genito\u00fcriner (%2-20), bron\u015fit\/pn\u00f6moni \u015feklinde seyreden pulmoner (%7), hepatit \u015feklinde seyreden gastrointestinal (%3-6), menenjit \u015feklinde seyreden n\u00f6rolojik (%2-7), endokardit \u015feklinde seyreden kardiyak (nadir), \u00fcveit \u015feklinde seyreden ok\u00fcler ve d\u00f6k\u00fcnt\u00fc \u015feklinde seyreden dermatolojik tutulumlar olabilir. Brusellozdan en s\u0131k \u00f6l\u00fcm nedeni infektif endokardittir.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Akut ve kronik bruselloz d\u0131\u015f\u0131nda baz\u0131 hastalarda \u201cuzam\u0131\u015f konvalesan d\u00f6nem\u201d de g\u00f6zlenebilir. Bu tablo, bruselloz tan\u0131s\u0131yla tedavi k\u00fcr\u00fcn\u00fc tamamlam\u0131\u015f ve antikor titreleri d\u00fc\u015fm\u00fc\u015f, hatta kaybolmu\u015f bir hastada, infeksiyonun baz\u0131 semptomlar\u0131n\u0131n, ate\u015f gibi objektif bulgular olmaks\u0131z\u0131n devam etmesidir. Uzam\u0131\u015f konvalesan d\u00f6nemin nedeni tam olarak bilinmemekle birlikte, yap\u0131lm\u0131\u015f psikolojik \u00e7al\u0131\u015fmalarda bu ki\u015filerde, genellikle bruselloz tan\u0131s\u0131ndan \u00f6nce olmak \u00fczere ki\u015filik bozukluklar\u0131n\u0131n daha s\u0131k g\u00f6r\u00fcld\u00fc\u011f\u00fc belirlenmi\u015ftir. Her durumda, bu tabloda antimikrobiyal tedavinin yarar\u0131 g\u00f6sterilmemi\u015ftir ve \u00f6nerilmemektedir (24).<\/p>\n<p class=\"p3\">Gebede bruselloz spontan d\u00fc\u015f\u00fck veya bebe\u011fe intrauterin bula\u015fma riski ta\u015f\u0131maktad\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>\u0130nsan plasentas\u0131nda eritritol bulunmamas\u0131na ra\u011fmen, \u00f6zellikle erken trimesterlerde <i>Brucella<\/i> spp. bakteriyemisi olanlarda d\u00fc\u015f\u00fck g\u00f6r\u00fclebilir. Brusellozdaki d\u00fc\u015f\u00fck riskinin, di\u011fer bakteriyemilerdeki d\u00fc\u015f\u00fck riskinden daha y\u00fcksek olup olmad\u0131\u011f\u0131 bilinmemektedir. Her durumda gebede brusellozun h\u0131zla tespit edilerek tedavi edilmesi fetus i\u00e7in hayat kurtar\u0131c\u0131 olabilir. Emzirmeyle anneden bebe\u011fe bula\u015fma nadir de olsa bildirilmi\u015ftir (24-27).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Akut brusellozda; ate\u015f, hepatosplenomegali, yayg\u0131n lenfadenomegali ve lokal tutulum \u015feklinde fizik muayene bulgular\u0131 olabilir. Bruselloz, \u00fclkemizde endemik bir hastal\u0131k olmas\u0131 nedeniyle, uzam\u0131\u015f ate\u015fle ba\u015fvuran hastalar\u0131n ay\u0131r\u0131c\u0131 tan\u0131s\u0131nda d\u00fc\u015f\u00fcn\u00fclmesi gereken hastal\u0131klar\u0131n en ba\u015f\u0131nda gelmektedir. Brusellozlu hastalar\u0131n kan say\u0131m\u0131nda anemi, l\u00f6kopeni, trombositopeni, pansitopeni gibi hematolojik anormallikler olabilir.<\/p>\n<h3 class=\"p7\">Bruselloz Tan\u0131s\u0131<\/h3>\n<p class=\"p14\"><em><strong>K\u00fclt\u00fcr<\/strong><\/em><\/p>\n<p class=\"p3\">Brusellozlu hastalar\u0131n kan\u0131ndan, etkilenmi\u015f dokular\u0131ndan veya kemik ili\u011fi \u00f6rne\u011finden bakteri izole edilebilir. Tan\u0131da k\u00fclt\u00fcr \u00e7ok \u00f6nemlidir ve alt\u0131n standartt\u0131r; kan k\u00fclt\u00fcr\u00fc akut olgular\u0131n %70\u2019inde pozitiftir ve elde etmesi zor olmas\u0131na ra\u011fmen kemik ili\u011fi aspirasyonunun olgular\u0131n yakla\u015f\u0131k %92\u2019sinde pozitif olabilece\u011fi bildirilmektedir. Ancak <i>Brucella<\/i> spp.\u2019nin \u00fcremesi zor ve yava\u015f olup primer \u00f6rnekten \u00fcretilmesi 21 g\u00fcn kadar uzun s\u00fcrebilir. Kronik infeksiyonu olanlarda k\u00fclt\u00fcr\u00fcn pozitif olma olas\u0131l\u0131\u011f\u0131 d\u00fc\u015f\u00fckt\u00fcr. <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Laboratuvarda \u00f6rneklerle g\u00fcvenli bir \u015fekilde \u00e7al\u0131\u015f\u0131lmas\u0131 ve bula\u015fmalar\u0131n \u00f6n\u00fcne ge\u00e7ilmesi i\u00e7in, bruselloz d\u00fc\u015f\u00fcn\u00fclen hastalardan k\u00fclt\u00fcr i\u00e7in g\u00f6nderilen \u00f6rnekler konusunda laboratuvar mutlaka bilgilendirilmelidir. <i>Brucella <\/i>spp. otomatize kan k\u00fclt\u00fcr\u00fc sistemlerinde s\u0131kl\u0131kla \u00fc\u00e7 g\u00fcn i\u00e7inde \u00fcremektedir; mevcut kan k\u00fclt\u00fcr\u00fc sistemlerindeki be\u015f g\u00fcnl\u00fck ink\u00fcbasyon s\u00fcresi, \u00f6zellikle akut bruselloz olgular\u0131n\u0131n kan k\u00fclt\u00fcrlerinde <i>Brucella <\/i>spp.\u2019nin \u00fcremesi i\u00e7in de yeterlidir.<span class=\"Apple-converted-space\">\u00a0 <\/span>Ancak hastal\u0131k semptomlar\u0131 uzun s\u00fcredir devam edenlerde veya fokal infeksiyonlarla ba\u015fvuranlarda kan k\u00fclt\u00fcr \u015fi\u015felerinin ink\u00fcbasyon s\u00fcresinin iki haftaya uzat\u0131lmas\u0131 ve ink\u00fcbasyon s\u00fcresi sonunda bir pasaj yap\u0131larak \u00fcreme olup olmad\u0131\u011f\u0131n\u0131n kontrol edilmesi gerekebilir.<span class=\"Apple-converted-space\">\u00a0 <\/span>K\u00fclt\u00fcrde uygun koloni morfolojisinde Gram-negatif, oksidaz pozitif, \u00fcreaz pozitif kokobasiller \u00fcredi\u011finde <i>Brucella<\/i> akla gelmeli ve ileri tiplendirme yap\u0131lmal\u0131d\u0131r (\u015eekil 2). <i>Brucella<\/i> spp.\u2019nin tan\u0131mlanmas\u0131 ve tiplendirilmesinde klasik olarak biyokimyasal testler (boya duyarl\u0131l\u0131klar\u0131, H<sub>2<\/sub>S \u00fcretimi ve \u00fcreaz aktivitesi), faj lizisi, antiserum agl\u00fctinasyonu ve molek\u00fcler teknikler kullan\u0131lmaktad\u0131r (24-29). Mevcut ticari biyokimyasal tan\u0131mlama sistemleri yeterli de\u011fildir; <i>Brucella<\/i> spp. yanl\u0131\u015fl\u0131kla yak\u0131n t\u00fcrler olan <i>Ochrobactrum anthropi<\/i> veya <i>Ochrobactrum intermedium<\/i> veya <i>Haemophilus influenza<\/i>, <i>Bergeyella zoohelcum<\/i>, <i>Bordetella bronchiseptica<\/i> veya <i>Psychrobacter phenylpyruvicus<\/i> \u015feklinde tan\u0131mlanarak laboratuvardan edinilmi\u015f infeksiyonlar dahil ciddi sonu\u00e7lara yol a\u00e7abilir. Bu nedenle bu sistemlerin <i>Brucella<\/i> spp. tan\u0131mlamas\u0131nda kullan\u0131m\u0131 \u00f6nerilmemektedir.<span class=\"Apple-converted-space\">\u00a0 <\/span>Son y\u0131llarda mikroorganizmalar\u0131n tan\u0131mlanmas\u0131nda s\u0131kl\u0131kla kullan\u0131lan MALDI-TOF MS, <i>Brucella<\/i> spp. tan\u0131mlamas\u0131nda da h\u0131zl\u0131, ekonomik ve g\u00fcvenilir bir y\u00f6ntem olarak \u00f6ne \u00e7\u0131kmaktad\u0131r (30).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p14\"><strong><em>Serolojik Antikor Belirleme Testleri<\/em><\/strong><\/p>\n<p class=\"p3\">K\u00fclt\u00fcrde \u00fcreme olmayan veya k\u00fclt\u00fcr olanaklar\u0131 olmayan yerlerde serolojik testler olduk\u00e7a \u00f6nemlidir. <i>Brucella<\/i> bakterilerine kar\u015f\u0131 antikor yan\u0131t\u0131, semptomatik\/asemptomatik t\u00fcm hastalarda geli\u015fir; aylar ve hatta y\u0131llar boyunca kalabilir. Agl\u00fctinasyon testleri, bruselloz tan\u0131s\u0131n\u0131 do\u011frulamada kullan\u0131lan ve antikor yan\u0131t\u0131n\u0131 ara\u015ft\u0131ran serolojik testlerdir. P\u00fcrt\u00fcks\u00fcz koloni olu\u015fturan <i>Brucella <\/i>t\u00fcrlerine (<i>B. melitensis, B. abortus<\/i>, <i>B. suis<\/i>) kar\u015f\u0131 geli\u015fen h\u00fcmoral imm\u00fcn yan\u0131tta, O antijeni i\u00e7eren LPS (S-LPS)\u2019ye kar\u015f\u0131 geli\u015fen antikorlar bask\u0131nd\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>Brusellozun serolojik tan\u0131s\u0131nda kullan\u0131lan S-LPS antijeni s\u0131kl\u0131kla <i>B. abortus<\/i> S19 su\u015fundan elde edilir; insanda patojenik olan di\u011fer iki t\u00fcrde (<i>B. melitensis <\/i>ve <i>B. suis) <\/i>de bu antijen bulunmaktad\u0131r. Do\u011fal olarak bu antijenlerin kullan\u0131ld\u0131\u011f\u0131 RB, Wright STA gibi testlerle t\u00fcr d\u00fczeyinde ay\u0131r\u0131m yap\u0131lamamaktad\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>P\u00fcr\u00fczl\u00fc <i>Brucella<\/i> t\u00fcrleri olan <i>B. canis<\/i> ve <i>B. ovis<\/i>\u2019te ise LPS\u2019nin O zinciri yoktur ve bu nedenle infeksiyonlar\u0131n\u0131n tan\u0131s\u0131 S-LPS antikorlar\u0131n\u0131n ara\u015ft\u0131r\u0131lmas\u0131yla konulamaz. LPS molek\u00fcl\u00fc, <i>Francisella tularensis, Escherichia coli O116 ve O157, Salmonella urbana, Yersinia enterocolitica O:9, Vibrio cholerae<\/i>, <i>Stenotrophomonas maltophilia<\/i> ve <i>Afipia clevelandensis<\/i> dahil bir\u00e7ok Gram-negatif bakteriyle \u00e7arpraz reaksiyon veren epitoplar ta\u015f\u0131maktad\u0131r. Bu nonspesifik reaksiyonlardan sorumlu olan antikorlar genellikle IgM tipindedir. <i>Brucella<\/i> t\u00fcrlerinin sitozolik proteinleri, \u00f6nemli \u00e7apraz reaksiyon g\u00f6stermezler, bu nedenle antijen olarak kullan\u0131labilece\u011fi d\u00fc\u015f\u00fcn\u00fclmektedir.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S5.V2.png\"><img loading=\"lazy\" decoding=\"async\" class=\"alignleft size-full wp-image-30433\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S5.V2.png\" alt=\"\" width=\"1526\" height=\"592\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S5.V2.png 1526w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S5.V2-390x151.png 390w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S5.V2-810x314.png 810w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S5.V2-768x298.png 768w\" sizes=\"auto, (max-width: 1526px) 100vw, 1526px\" \/><\/a>Brusellaya \u00f6zg\u00fc serolojik agl\u00fctinasyon testlerinde, bakteriyel antijenlerin hasta serumundaki \u00f6zg\u00fcl antikorlarla direkt agl\u00fctinasyonuna bak\u0131l\u0131r. Rose Bengal, Wright STA, brusella mikroagl\u00fctinasyon testi (BMAT) (k\u00fc\u00e7\u00fck plaklarda yap\u0131lan SAT), 2-merkaptoetanol STA, Coombs\u2019lu STA ve imm\u00fcn yakalama agl\u00fctinasyon testlerinin (<i>Brucella<\/i>Capt) hepsinde S-LPS\u2019ye kar\u015f\u0131 antikorlar ara\u015ft\u0131r\u0131l\u0131r. Rose Bengal kart testi, h\u0131zl\u0131 testtir. Duyarl\u0131l\u0131\u011f\u0131n\u0131n olduk\u00e7a y\u00fcksek (&gt;%90) olmas\u0131 ama \u00f6zg\u00fcll\u00fc\u011f\u00fcn\u00fcn d\u00fc\u015f\u00fck olmas\u0131 nedeniyle tarama i\u00e7in kullan\u0131labilece\u011fi belirtilmektedir. Wright STA testi referans y\u00f6ntem olup hem IgM, hem IgG, hem de IgA s\u0131n\u0131f\u0131 antikorlar belirlenir. \u0130nsanlarda <i>Brucella<\/i> infeksiyonlar\u0131na kar\u015f\u0131 imm\u00fcn yan\u0131t farkl\u0131l\u0131k g\u00f6stermekle birlikte genel olarak brusellozun ilk haftas\u0131nda IgM, ard\u0131ndan 2. haftada IgG ve sonras\u0131nda IgA yan\u0131t\u0131 geli\u015fir. Hastal\u0131\u011f\u0131n erken d\u00f6nemlerinde hepsinin titresi artar ve yakla\u015f\u0131k 4. haftada en y\u00fcksek seviyelerine ula\u015f\u0131r. Uzam\u0131\u015f olgularda IgM konsantrasyonlar\u0131 d\u00fc\u015febilir ve esas olarak IgG ve IgA yan\u0131t\u0131 vard\u0131r; ancak tamamen iyile\u015fmi\u015f olgular\u0131n %20-25\u2019inde tedaviden sonraki ilk y\u0131lda bile IgM antikorlar\u0131 belirlenmi\u015ftir. \u0130lerleyen s\u00fcre\u00e7te non-agl\u00fctinan (inkomplet) antikorlar, agl\u00fctinanlardan daha fazla hale gelebilir ki bu da klasik STA\u2019n\u0131n yalanc\u0131 negatifli\u011fine yol a\u00e7abilir. Bu non-agl\u00fctinan antikorlar, agl\u00fctinasyon testine Coombs serumunun da eklenmesiyle (Coombs STA) g\u00f6sterilebilir. <i>Brucella<\/i>Capt, ayn\u0131 test i\u00e7inde hem agl\u00fctinan IgG ve IgM\u2019yi hem de non-agl\u00fctinan IgG antikorlar\u0131n\u0131 g\u00f6sterebilen bir testtir. Erken antimikrobik tedavi sitozolik <i>Brucella<\/i> proteinlerine kar\u015f\u0131 antikor yan\u0131t\u0131n\u0131 azalt\u0131rken, LPS antikor yan\u0131t\u0131n\u0131 daha az oranda etkiler. IgG ve IgA\u2019da h\u0131zl\u0131 bir d\u00fc\u015f\u00fc\u015f olmas\u0131 genellikle antimikrobik tedaviye iyi bir yan\u0131t oldu\u011funu g\u00f6sterirken, titrelerin art\u0131\u015f\u0131 veya \u00e7ok y\u00fcksek antikor seviyelerinin d\u00fc\u015fmemesi tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131n\u0131, rezid\u00fcel hastal\u0131\u011f\u0131 veya relaps\u0131 d\u00fc\u015f\u00fcnd\u00fcr\u00fcr. Ancak \u00f6zellikle fokal komplikasyonu ve ilk tan\u0131 an\u0131ndaki titreleri \u00e7ok y\u00fcksek olan hastalarda antikor titrelerinin daha yava\u015f d\u00fc\u015febilece\u011fi, bu nedenle tedavi sonunda pozitifli\u011fin devam etmesinin her zaman tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131n\u0131, kronikle\u015fmeyi veya relaps\u0131 g\u00f6stermeyece\u011fi de ak\u0131lda tutulmal\u0131d\u0131r; hastalar esas olarak klinik semtom ve bulgular\u0131na g\u00f6re de\u011ferlendirilmelidir.<span class=\"Apple-converted-space\">\u00a0 <\/span>Relaps durumunda genellikle IgG seviyelerinde belirgin, IgA seviyelerinde orta dereceli bir art\u0131\u015f olurken, IgM seviyelerinde art\u0131\u015f olmaz. Wright STA testinde iki hafta ara ile al\u0131nan akut ve konvalesan serumda titrenin \u22654 kat artmas\u0131 veya \u22651\/160 tek titre pozitifli\u011fi (endemik b\u00f6lgelerde \u22651\/320) olmas\u0131 tan\u0131sal olarak kabul edilir (24-29).<span class=\"Apple-converted-space\">\u00a0 <\/span>\u015eekil 5\u2019te brusellozun evrelerine g\u00f6re antikorlar\u0131n seyri g\u00f6sterilmi\u015ftir.<\/p>\n<p class=\"p3\">Serolojik agl\u00fctinasyon testlerinin en \u00f6nemli sorunlar\u0131 infeksiyonun erken evrelerinde yalanc\u0131 negatiflikleri, IgM tipi antikorlar\u0131n yukar\u0131da belirtilmi\u015f baz\u0131 Gram-negatif \u00e7omaklarla \u00e7apraz reaksiyon vermesi, \u00e7ok fazla miktarda antikor olmas\u0131 veya \u00f6zg\u00fcl olmayan serum fakt\u00f6rleri nedeniyle d\u00fc\u015f\u00fck dilusyonlarda agl\u00fctinasyonun inhibisyonu (prezon olay\u0131), inkomplet antikorlar nedeniyle yalanc\u0131 negatiflik olmas\u0131 ve <i>B. canis<\/i> infeksiyonlar\u0131n\u0131n tan\u0131s\u0131n\u0131 koyamamalar\u0131d\u0131r. Bu durumlar i\u00e7in s\u0131ras\u0131yla testin 2-3 hafta sonra tekrarlanmas\u0131, IgM cinsi antikorlar\u0131n merkaptoetanol veya daha az toksik olan ditiyotreitol gibi maddelerle par\u00e7alanarak STA testi yap\u0131lmas\u0131, serumun ileri dil\u00fcsyonlar\u0131n\u0131n (&gt;1\/320) yap\u0131lmas\u0131, Coombs\u2019lu STA veya <i>Brucella<\/i>Capt testleriyle yap\u0131lmas\u0131 ve t\u00fcre \u00f6zg\u00fc bir test kullan\u0131lmas\u0131 \u00f6nerilmektedir (29). <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Tan\u0131 i\u00e7in gerek LPS gerek di\u011fer antijenlerin kullan\u0131ld\u0131\u011f\u0131 ELISA ve benzeri y\u00f6ntemlerle yap\u0131lan serolojik testler de bulunmaktad\u0131r. Ancak bu testler her yerde bulunamamalar\u0131, duyarl\u0131l\u0131k, \u00f6zg\u00fcll\u00fck sorunlar\u0131 gibi nedenlerle halen agl\u00fctinasyon testlerinin yerine ge\u00e7memektedir.<\/p>\n<p class=\"p14\"><strong><em>N\u00fckleik Asit Amplifikasyon Testleri<span class=\"Apple-converted-space\">\u00a0<\/span><\/em><\/strong><\/p>\n<div id=\"attachment_26979\" style=\"width: 2196px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S6.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-26979\" class=\"wp-image-26979 size-full\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S6.png\" alt=\"\" width=\"2186\" height=\"2233\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S6.png 2186w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S6-255x260.png 255w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S6-529x540.png 529w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-S6-768x785.png 768w\" sizes=\"auto, (max-width: 2186px) 100vw, 2186px\" \/><\/a><p id=\"caption-attachment-26979\" class=\"wp-caption-text\"><strong>\u015eekil 6.<\/strong> Bruselloz D\u00fc\u015f\u00fcn\u00fclen Olgularda Tan\u0131 Testleri \u0130\u00e7in Kullan\u0131m Algoritmas\u0131<\/p><\/div>\n<p class=\"p3\">Ba\u015fta PCR olmak \u00fczere olduk\u00e7a duyarl\u0131 y\u00f6ntemler olan n<i>\u00fckleik <\/i>asit amplifikasyon testleri<i> <\/i>(NAAT), hem brusellozun hem de fokal komplikasyonlar\u0131n tan\u0131s\u0131nda gittik\u00e7e artan oranlarda kullan\u0131lmaktad\u0131r. \u00c7ok duyarl\u0131 olmalar\u0131, gittik\u00e7e kolayla\u015fan yap\u0131lma \u015fekilleri, h\u0131zl\u0131 ve g\u00fcvenilir olmalar\u0131 gibi avantajlar\u0131 bulunmakla birlikte, semptomu olmayan hastalarda da pozitif olarak belirlenebilmeleri, dolay\u0131s\u0131yla aktif infeksiyonu belirlemedeki sorunlar\u0131, pahal\u0131 olmalar\u0131, kolay ula\u015f\u0131lamamalar\u0131 gibi bir\u00e7ok dezavantaj\u0131 da bulunmaktad\u0131r. Amerikan Hastal\u0131k Kontrol ve Korunma Merkezleri (CDC) taraf\u0131ndan klinik \u00f6rneklerde PCR ile <i>Brucella<\/i>\u00a0DNA belirlenmesi, olas\u0131 laboratuvar tan\u0131 \u00f6l\u00e7\u00fct\u00fc olarak \u00f6nerilmektedir (11,29,31). Bruselloz d\u00fc\u015f\u00fcn\u00fclen olgularda tan\u0131 testlerinin kullan\u0131m\u0131 i\u00e7in, rehber \u00e7al\u0131\u015fmas\u0131nda elde edilen kan\u0131tlara dayan\u0131larak olu\u015fturulan algoritma \u015eekil 6\u2019da sunulmu\u015ftur.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h3 class=\"p7\">Bruselloz Olgu Tan\u0131mlar\u0131<\/h3>\n<div id=\"attachment_26985\" style=\"width: 2195px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T2-1.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-26985\" class=\"size-full wp-image-26985\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T2-1.png\" alt=\"\" width=\"2185\" height=\"2039\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T2-1.png 2185w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T2-1-279x260.png 279w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T2-1-579x540.png 579w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T2-1-768x717.png 768w\" sizes=\"auto, (max-width: 2185px) 100vw, 2185px\" \/><\/a><p id=\"caption-attachment-26985\" class=\"wp-caption-text\"><strong>Tablo 2.<\/strong> Bruselloz \u0130\u00e7in \u00d6nerilen Olgu Tan\u0131mlar\u0131<\/p><\/div>\n<p class=\"p3\">Bruselloz i\u00e7in T.C. Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131, WHO ve CDC taraf\u0131ndan hastal\u0131\u011f\u0131n s\u00fcrveyans\u0131nda kullan\u0131lmas\u0131 \u00f6nerilen olgu tan\u0131mlar\u0131 Tablo 2\u2019de verilmi\u015ftir. <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h3 class=\"p7\">N\u00f6robruselloz Tan\u0131 \u00d6l\u00e7\u00fctleri<span class=\"Apple-converted-space\">\u00a0<\/span><\/h3>\n<p class=\"p3\">Laboratuvar taraf\u0131ndan do\u011frulanm\u0131\u015f bruselloz tan\u0131s\u0131 olan hastada (serum SAT \u22651:160 veya k\u00fclt\u00fcr pozitif) a\u015fa\u011f\u0131dakilerden en az birisinin varl\u0131\u011f\u0131;<\/p>\n<ul>\n<li class=\"p15\">N\u00f6robruselloz ile uyumlu semptom ve bulgu (kronik ba\u015f a\u011fr\u0131s\u0131, insomnia, depresyon, konf\u00fczyon, ki\u015filik de\u011fi\u015fiklikleri, n\u00f6rolojik tutulumlar),<\/li>\n<li class=\"p10\">BOS k\u00fclt\u00fcr pozitifli\u011fi ve\/veya BOS antikor pozitifli\u011fi,<\/li>\n<li class=\"p10\">BOS lenfositoz, protein y\u00fcksekli\u011fi, glukoz d\u00fc\u015f\u00fckl\u00fc\u011f\u00fc ve\/veya radyolojik bulgular (n\u00f6rolojik tutulumu destekleyen kraniyal manyetik rezonans g\u00f6r\u00fcnt\u00fcleme (MRI) veya bilgisayarl\u0131 tomografi (BT) bulgular\u0131) (33-54).<\/li>\n<\/ul>\n<p class=\"p3\">Bu \u00f6l\u00e7\u00fctler d\u0131\u015f\u0131nda baz\u0131 \u00e7al\u0131\u015fmalarda sadece serum ve\/veya BOS\u2019ta brusella antikorlar\u0131n\u0131n \u201cenzyme-linked immunosorbent assay\u201d (ELISA) ile saptanmas\u0131yla n\u00f6robruselloz tan\u0131s\u0131 konulmu\u015ftur (42-50). Serum ve BOS\u2019ta brusella antikorlar\u0131n\u0131n sadece imm\u00fcnofloresan (IFA) veya kompleman fiksasyon testleriyle g\u00f6sterilmesi yoluyla tan\u0131 konulan az say\u0131da olgu da bildirilmi\u015ftir (51,52). Bir olgu sunumunda ve 51 olgunun incelendi\u011fi bir \u00e7al\u0131\u015fmadaki 27 olguda sadece serum veya BOS\u2019ta PCR pozitifli\u011fine g\u00f6re n\u00f6robruselloz tan\u0131s\u0131 konulmu\u015ftur (53,54).<\/p>\n<h3 class=\"p3\"><b><i><\/i><\/b><em>Brucella<\/em> spp. Antimikrobiyal Duyarl\u0131l\u0131k Testleri<\/h3>\n<p class=\"p3\"><span class=\"s3\">Bir hastan\u0131n herhangi bir klinik \u00f6rne\u011finde <i>Brucella<\/i> spp. \u00fcremesi saptand\u0131\u011f\u0131nda, referans laboratuvarlar d\u0131\u015f\u0131nda antimikrobiyal duyarl\u0131l\u0131k testlerinin yap\u0131lmas\u0131, sonu\u00e7lar\u0131n bildirilmesi genel olarak gerekli ve uygun de\u011fildir. Diren\u00e7 nadiren sorundur ve mutlaka referans laboratuvarlarda tan\u0131mlanmal\u0131d\u0131r. <i>In vitro<\/i> duyarl\u0131l\u0131k sonu\u00e7lar\u0131yla klinik etkinlik birbiriyle korele olmayabilir. Baz\u0131 durumlarda kullan\u0131lmamas\u0131 gereken ajanlara da duyarl\u0131l\u0131k tan\u0131mlanarak tedavinin yanl\u0131\u015f y\u00f6nlendirilmesine neden olunabilir. Uygun tedaviye ba\u015flanabilmesi i\u00e7in \u00f6nemli olan bakterinin do\u011fru tan\u0131mlanmas\u0131d\u0131r (12). <i>Brucella<\/i> spp. i\u00e7in genel olarak kabul edilen bir antimikrobiyal duyarl\u0131l\u0131k testi (ADT) standard\u0131 ve kullan\u0131lan antimikrobikler i\u00e7in s\u0131n\u0131r de\u011ferleri bulunmamaktad\u0131r. Bu da g\u00fcnl\u00fck pratikte ADT testlerinde ve kullan\u0131lan s\u0131n\u0131r de\u011ferlerde \u00e7e\u015fitlili\u011fe yol a\u00e7makta, ADT test sonu\u00e7lar\u0131n\u0131n \u00fclkeler ve laboratuvarlar aras\u0131nda kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131n\u0131 zorla\u015ft\u0131rmaktad\u0131r. <i>Brucella <\/i>spp. zor \u00fcreyen bakterilerdir ve klinik \u00f6rneklerden ilk izolasyonlar\u0131 i\u00e7in kan i\u00e7eren k\u00fclt\u00fcr plaklar\u0131 ve<span class=\"Apple-converted-space\">\u00a0 <\/span>%5\u2019lik CO<sub>2<\/sub>\u2019li ortamda ink\u00fcbasyon \u00f6nerilmektedir. Klinik ve Laboratuvar Standartlar\u0131 Enstit\u00fcs\u00fc (CLSI) taraf\u0131ndan <i>Brucella<\/i> spp. i\u00e7in bir s\u0131v\u0131 mikrodil\u00fcsyon (BMD) ADT tan\u0131mlanm\u0131\u015ft\u0131r; bu standartta besiyeri olarak <i>Brucella<\/i> buyyonu (BB) kullan\u0131lmas\u0131 \u00f6nerilmektedir (55). Bunun d\u0131\u015f\u0131nda baz\u0131 maddeler eklenmi\u015f Mueller\u2013Hinton buyyonuyla BMD, <i>Brucella<\/i> agarla agar dil\u00fcsyon y\u00f6ntemleri de kullan\u0131lmaktad\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>Klinik ve Laboratuvar Standartlar\u0131 Enstit\u00fcs\u00fc standard\u0131nda RIF ve florokinolonlar i\u00e7in s\u0131n\u0131r de\u011ferler tan\u0131mlanmam\u0131\u015ft\u0131r, di\u011fer antimikrobiyaller i\u00e7inse sadece duyarl\u0131l\u0131k s\u0131n\u0131r de\u011ferleri verilmi\u015f, diren\u00e7li s\u0131n\u0131r de\u011feri tan\u0131mlanmam\u0131\u015ft\u0131r. Trimetoprim-s\u00fclfametoksazol i\u00e7in belirlenen minimum inhibit\u00f6r konsantrasyonu (M\u0130K) de\u011ferleri, s\u0131n\u0131r de\u011fere \u00e7ok yak\u0131n k\u00fcmelendi\u011fi i\u00e7in, vah\u015fi su\u015flarda s\u0131kl\u0131kla \u201corta duyarl\u0131\u201d, \u201cdiren\u00e7li\u201d sonu\u00e7lara neden olmaktad\u0131r; ilgili su\u015flar\u0131n tam genom dizilemelerinde RIF diren\u00e7 fenotipiyle ili\u015fkili genomik bir de\u011fi\u015fim saptanmamas\u0131na ra\u011fmen RIF M\u0130K de\u011ferleri beklenmedik \u015fekilde y\u00fcksek \u00e7\u0131kmaktad\u0131r. Avrupa Antimikrobiyal Duyarl\u0131l\u0131k Testi Komitesi (EUCAST), ISO 20776 standard\u0131n\u0131 esas alarak, ADT\u2019de gereksinime g\u00f6re ekleme yap\u0131lmam\u0131\u015f, katyonu ayarlanm\u0131\u015f Mueller\u2013Hinton buyyonu (CAMHB), baz\u0131 maddeler eklenmi\u015f CAMHB, yeterli \u00fcreme olmamas\u0131 halindeyse \u201cfastidious anaerobe agar\u201d (veya buyyon) \u00f6nermektedir (56). K\u00fclt\u00fcr besiyerleri ve ink\u00fcbasyon konusunda CLSI \u00f6nerileri, ISO 20776 standard\u0131n\u0131 kar\u015f\u0131lamad\u0131\u011f\u0131 i\u00e7in k\u0131sa s\u00fcre \u00f6nce Avrupa Antimikrobiyal Duyarl\u0131l\u0131k Testi Komitesi (EUCAST) temsilcilerinin kontrol\u00fcnde ve Avrupa <i>Brucella<\/i> referans laboratuvarlar\u0131n\u0131n yer ald\u0131\u011f\u0131 bir Avrupa Birli\u011fi (AB) \u00e7al\u0131\u015fma grubu, farkl\u0131 k\u00fclt\u00fcr besiyerleri, k\u00fclt\u00fcr ko\u015fullar\u0131 ve ADT\u2019lerini kar\u015f\u0131la\u015ft\u0131rarak CLSI M45 dok\u00fcman\u0131n\u0131n ISO 20776 standard\u0131na adaptasyonunu sa\u011flam\u0131\u015ft\u0131r. S\u00f6z konusu \u00e7al\u0131\u015fmada, y\u00f6ntemi de\u011ferlendirmek i\u00e7in standart operasyon prosed\u00fcr\u00fc (SOP) olu\u015fturulmu\u015f ve laboratuvarlar aras\u0131 validasyon \u00e7al\u0131\u015fmalar\u0131 yap\u0131lm\u0131\u015ft\u0131r. \u00c7al\u0131\u015fmalarda toplam 57 vah\u015fi <i>B. melitensis<\/i> su\u015fu ve bir diren\u00e7li su\u015f kullan\u0131lm\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>Sonu\u00e7 olarak; <i>B. melitensis<\/i> i\u00e7in yap\u0131lacak BMD ADT i\u00e7in CAMHB\u2019un uygun oldu\u011funa karar verilmi\u015f ve BMD plaklar\u0131n\u0131n do\u011fru inokulumla haz\u0131rlanmas\u0131 ve %5 CO<sub>2<\/sub> ortam yerine normal ortamda 48 saat ink\u00fcbe edilmesi gerekti\u011fi bildirilmi\u015ftir. \u00d6zellikle TMP-SMX M\u0130K de\u011ferleri okunurken %80\u2019lik \u00fcreme inhibisyonun dikkate al\u0131nmas\u0131 gerekti\u011fi vurgulanm\u0131\u015ft\u0131r (57). <span class=\"Apple-converted-space\">\u00a0<\/span><\/span><\/p>\n<h3 class=\"p3\">Brusellozun Tedavisi<span class=\"Apple-converted-space\">\u00a0<\/span><\/h3>\n<p class=\"p3\">Bruselloz, h\u00fccre i\u00e7ine yerle\u015febilen bir patojen olmas\u0131 nedeniyle, yinelemeleri ve kronikle\u015fmeyi \u00f6nlemek amac\u0131yla uzun s\u00fcreli ve kombinasyon tedavisi gerektirir. Kullan\u0131lacak ajanlardan birinin h\u00fccre i\u00e7ine ge\u00e7i\u015finin iyi olmas\u0131 \u00f6nemlidir. Tedavi kombinasyonlar\u0131nda kullan\u0131labilen antibiyotikler tetrasiklin (TET), DOX, STREP, RIF, GEN, TMP-SMX ve siprofloksasin (CIP)\u2019nden olu\u015fur. N\u00f6robruselloz olgular\u0131nda ise CRO kombinasyonda yer alabilen bir ajand\u0131r. Doksisiklin, h\u00fccre i\u00e7ine iyi ge\u00e7ebilmesi ve h\u00fccre i\u00e7i bakterilere g\u00fc\u00e7l\u00fc etkisi nedeniyle tedavinin temelini olu\u015fturur.<span class=\"Apple-converted-space\">\u00a0 <\/span>Rifampisin+DOX kombinasyonunun, oral bir rejim olmas\u0131 nedeniyle uygulama kolayl\u0131\u011f\u0131 vard\u0131r ve bu nedenle WHO taraf\u0131ndan ilk se\u00e7enek tedavi olarak \u00f6nerilmektedir; ancak klinik ara\u015ft\u0131rmalarda bu tedavi rejimiyle relaps riskinin daha y\u00fcksek olabilece\u011fi bildirilmektedir. Doksisiklin-aminoglikozid kombinasyonunda (ilk \u00fc\u00e7 hafta STREP veya ilk bir hafta GEN \u015feklinde) ise relaps riskinin daha d\u00fc\u015f\u00fck olabilece\u011fi rapor edilmi\u015ftir. Fokal komplikasyon olmayan hastal\u0131kta tedavi s\u00fcresi alt\u0131 haftayken, fokal tutulum olan ki\u015filerde tedavi s\u00fcresi 3-6 aya kadar uzat\u0131labilir (11,58).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p16\">Trimetoprim-s\u00fclfametoksazol, bruselloz tedavisinde gerek 2\u2019li gerekse 3\u2019l\u00fc kombinasyonlarda yayg\u0131n kullan\u0131lan ila\u00e7lardan biridir (10); TMP-SMX+RIF kombinasyonu \u00f6zellikle pediatrik veya gebe hastalarda kullan\u0131lm\u0131\u015ft\u0131r. Trimetoprim-s\u00fclfametoksazol (8 mg\/kg\/g\u00fcn TMP dozu olacak \u015fekilde) + RIF\u2019le, TMP-SMX+DOX kombinasyonlar\u0131n\u0131 kar\u015f\u0131la\u015ft\u0131ran randomize kontroll\u00fc bir \u00e7al\u0131\u015fmada, TMP-SMX+DOX kombinasyonuyla tedavi ba\u015far\u0131s\u0131n\u0131n daha y\u00fcksek oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr [%95 g\u00fcven aral\u0131\u011f\u0131 (GA)=0.174-0.862; \u201codds ratio\u201d (OR)=0.387; <i>p<\/i>=0.020] (59).<\/p>\n<p class=\"p3\"><span class=\"s1\">Trimetoprim-s\u00fclfametoksazol<\/span> \u00f6zellikle komplike bruselloz olgular\u0131nda olmak \u00fczere bir\u00e7ok \u00fclkede 3\u2019l\u00fc kombinasyonlar i\u00e7inde yayg\u0131n olarak kullan\u0131lmakta ve %90 civar\u0131 tedavi ba\u015far\u0131s\u0131 oldu\u011fu belirtilmektedir. Ancak komplike brusellozda TMP-SMX i\u00e7eren 3\u2019l\u00fc rejimleri \u00f6nermek i\u00e7in yeterli kan\u0131t bulunmamaktad\u0131r. Baz\u0131 yazarlar, WHO taraf\u0131ndan \u00f6nerilen DOX-RIF rejimindeki y\u00fcksek relaps riski g\u00f6z \u00f6n\u00fcne al\u0131nd\u0131\u011f\u0131nda, TMP-SMX\u2019in bu rejime eklenebilece\u011fini d\u00fc\u015f\u00fcnmektedir (11). <i>Brucella<\/i> spp.\u2019de TMP-SMX\u2019e kar\u015f\u0131 diren\u00e7 geli\u015febilmesi konusunda uyar\u0131lar da yap\u0131lmakla birlikte (12) yukar\u0131daki \u201c<b><i>Brucella <\/i>spp. Antimikrobiyal Duyarl\u0131l\u0131k Testleri\u201d <\/b>b\u00f6l\u00fcm\u00fcnde<b> <\/b>de belirtildi\u011fi gibi <i>Brucella<\/i> spp.\u2019de TMP-SMX direncinin tan\u0131mlanmas\u0131nda gerek uygun besiyerlerinin kullan\u0131m\u0131 gerekse M\u0130K de\u011ferlerinin okunmas\u0131ndaki sorunlar konusunda dikkatli olunmal\u0131d\u0131r. Eldeki veriler, TMP-SMX\u2019in bruselloz tedavisinde, \u00f6zellikle DOX\u2019lu kombinasyonlar i\u00e7inde yer alabilece\u011fini, ancak ek \u00e7al\u0131\u015fmalara gereksinim oldu\u011funu d\u00fc\u015f\u00fcnd\u00fcrmektedir.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<div id=\"attachment_31469\" style=\"width: 1308px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T3-2-scaled.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-31469\" class=\"wp-image-31469 size-full\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T3-2-scaled.png\" alt=\"\" width=\"1298\" height=\"2560\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T3-2-scaled.png 1298w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T3-2-132x260.png 132w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T3-2-274x540.png 274w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T3-2-768x1514.png 768w\" sizes=\"auto, (max-width: 1298px) 100vw, 1298px\" \/><\/a><p id=\"caption-attachment-31469\" class=\"wp-caption-text\"><strong>Tablo 3.<\/strong> Bruselloz Olgular\u0131nda Tedavi \u00d6nerileri<\/p><\/div>\n<p class=\"p3\">Tablo 3\u2019te, kan\u0131t olmas\u0131 halinde rehberdeki analizlerle elde edilen sonu\u00e7lara g\u00f6re, kan\u0131t olmayan durumlarda ise rehber grubunda yer alan uzmanlar\u0131n \u00f6nerisiyle yap\u0131lm\u0131\u015f bruselloz tedavi \u00f6nerileri sunulmu\u015ftur. <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p16\"><span class=\"s6\">Kimi <i>in vitro<\/i> \u00e7al\u0131\u015fmalarda azitromisin (AZM)\u2019in de <i>Brucella<\/i> spp.\u2019ye etkili olabilece\u011fi bildirilmi\u015ftir (60). Bir hayvan \u00e7al\u0131\u015fmas\u0131nda, profilaktik AZM\u2019nin hem d\u00fc\u015f\u00fck hem de y\u00fcksek d\u00fczey <i>B. melitensis<\/i>\u2019e maruz b\u0131rak\u0131lan farelerde etkili oldu\u011fu g\u00f6sterilmi\u015ftir (61). <\/span>G\u00f6zlemsel bir klinik \u00e7al\u0131\u015fmada, AZM-GEN kombinasyonuyla 10 hastan\u0131n d\u00f6rd\u00fc ba\u015far\u0131yla tedavi edilirken, \u00fc\u00e7\u00fcnde relaps, ikisinde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015f, birinde ise istenmeyen etkiler nedeniyle tedavi de\u011fi\u015fikli\u011fi yap\u0131lmas\u0131 gerekmi\u015ftir (62). <span class=\"s6\">Ancak k\u0131sa s\u00fcre \u00f6nce yap\u0131lm\u0131\u015f bir <i>in vitro<\/i> \u00e7al\u0131\u015fmada Bosna-Hersek\u2019ten izole edilmi\u015f 108 <i>B. melitensis<\/i> su\u015funun &gt;%90\u2019\u0131nda<span class=\"Apple-converted-space\">\u00a0 <\/span>AZM direnci belirlendi\u011fi bildirilmi\u015ftir (63). <\/span>Yine \u00fclkemizde yap\u0131lm\u0131\u015f bir <i>in vitro<\/i> \u00e7al\u0131\u015fmada da AZM\u2019nin <i>B. melitensis<\/i> su\u015flar\u0131na kar\u015f\u0131 etkinli\u011finin s\u0131n\u0131rl\u0131 oldu\u011fu ve test edilen 73 su\u015fun %50\u2019sinde diren\u00e7 belirlendi\u011fi bildirilmi\u015ftir (64).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p16\">Eldeki veriler, AZM\u2019nin bruselloz tedavisinde, di\u011fer alternatifler oldu\u011fu s\u00fcrece de\u011ferlendirilmemesi gerekti\u011fini d\u00fc\u015f\u00fcnd\u00fcrmekle birlikte, ek \u00e7al\u0131\u015fmalara gereksinim oldu\u011fu a\u00e7\u0131kt\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h3 class=\"p7\">Hayvan Brusellozunun Kontrol\u00fc ve \u00d6nlenmesi<\/h3>\n<p class=\"p3\">Hayvan brusellozunun kontrol\u00fc ve \u00f6nlenmesi,<b> <\/b>genel olarak duyarl\u0131 hayvanlar\u0131n a\u015f\u0131lanmas\u0131 ve infekte hayvanlar\u0131n taranarak kesilmesi \u015feklinde sa\u011flan\u0131r. Bir b\u00f6lgede hayvanlarda hastal\u0131\u011f\u0131n prevalans\u0131 &gt;%5 ise t\u00fcm hayvanlar\u0131n (gen\u00e7 ve eri\u015fkin) kitlesel olarak a\u015f\u0131lanmas\u0131, %1-5 aras\u0131ndaysa gen\u00e7 hayvanlar\u0131n a\u015f\u0131lanmas\u0131 ve tarama\/kesme uygulamalar\u0131n\u0131n bir arada kullan\u0131lmas\u0131, &lt;%1<span class=\"Apple-converted-space\">\u00a0 <\/span>olmas\u0131 halindeyse tarama\/kesme \u015feklinde bir program uygulanmas\u0131 gerekir.<span class=\"Apple-converted-space\">\u00a0 <\/span>Bu yakla\u015f\u0131mlara ek olarak infeksiyon yay\u0131l\u0131m\u0131n\u0131 engelleyecek genel hijyen kurallar\u0131na uyumun art\u0131r\u0131lmas\u0131 ve hayvan hareketlerinin kontrol\u00fc de s\u0131kl\u0131kla gerekir.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">\u00dclkemizde 2011 y\u0131l\u0131nda yap\u0131lm\u0131\u015f bir \u00e7al\u0131\u015fmada s\u00fcr\u00fclerde seropozitiflik oranlar\u0131n\u0131n s\u0131\u011f\u0131rlar i\u00e7in %6.9, koyunlar i\u00e7inse %30 olarak belirlenmesiyle 1 Ocak 2012 tarihinden itibaren hayvan brusellozunun \u00f6nlenmesinde subkutan a\u015f\u0131lama durdurularak konjunktival canl\u0131, aten\u00fce <i>B. melitensis<\/i> Rev\u20101 ve canl\u0131, aten\u00fce <i>B. abortus<\/i> S-19 a\u015f\u0131lar\u0131yla kitlesel a\u015f\u0131lamaya ge\u00e7ilmi\u015ftir.<span class=\"Apple-converted-space\">\u00a0 <\/span>Bu uygulamayla s\u00fcr\u00fc prevalans\u0131nda \u00f6nemli azalma g\u00f6r\u00fclm\u00fc\u015f ve ortalama %12.3\u2019e d\u00fc\u015fm\u00fc\u015ft\u00fcr. Bu kitlesel a\u015f\u0131lamalar\u0131n prevalans\u0131n %5\u2019in alt\u0131na d\u00fc\u015fmesine kadar devam etmesi planlanmaktad\u0131r (21).<\/p>\n<h3 class=\"p7\">\u0130nsan Brusellozunun \u00d6nlenmesi<span class=\"Apple-converted-space\">\u00a0<\/span><\/h3>\n<p class=\"p3\">\u0130nsan brusellozunun \u00f6nlenebilmesi i\u00e7in \u00e7iftlik hayvanlar\u0131nda hastal\u0131\u011f\u0131n kontrol alt\u0131na al\u0131nmas\u0131 en \u00f6nemli basamakt\u0131r. \u0130kinci \u00f6nlem \u00e7i\u011f s\u00fct\/s\u00fct \u00fcr\u00fcnlerinin t\u00fcketilmemesi ve t\u00fcm s\u00fctlerin past\u00f6rizasyonudur.<span class=\"Apple-converted-space\">\u00a0 <\/span><i>Brucella<\/i> spp., WHO Risk Grubu 3 patojendir; \u00e7al\u0131\u015fan ki\u015fi i\u00e7in riskliyken, toplum i\u00e7in risk te\u015fkil etmeyen mikroorganizma grubunda yer al\u0131r. Ancak laboratuvar ortam\u0131ndan en kolay bula\u015fan patojenlerdendir. Klinik \u00f6rneklerde bulunan bakterilerin say\u0131s\u0131 bula\u015fmada \u00f6nemlidir; kan ve biyopsi \u00f6rneklerinde, testi \u00e7al\u0131\u015fan ki\u015fiye \u00f6nemli risk olu\u015fturacak say\u0131da bakteri nadiren bulunur, ama yine de t\u00fcm kan ve biyopsi \u00f6rnekleri en az Biyog\u00fcvenlik Seviye 2 (BSL-2) ko\u015fullar\u0131nda \u00e7al\u0131\u015f\u0131lmal\u0131d\u0131r. <i>Brucella <\/i>spp.\u2019nin \u00fcretilmi\u015f oldu\u011fu besiyerlerindeyse tehlikeli say\u0131da mikroorganizma bulundu\u011fu i\u00e7in \u00e7ok daha ciddi \u00f6nlemler al\u0131nmal\u0131d\u0131r. Bu a\u015famada BSL-3 ortamlar ve uygulamalar gereklidir. Ek olarak, <i>Brucella<\/i> spp. CDC\u2019nin biyolojik silah amac\u0131yla kullan\u0131labilecek potansiyel ajanlar listesinde A kategorisinde yer almaktad\u0131r. Klinik laboratuvarlarda uygun g\u00fcvenlik \u00f6nlemlerinin al\u0131nmas\u0131 ve mezbaha gibi yerlerde uygun koruyucu giysilerin kullan\u0131lmas\u0131 al\u0131nabilecek di\u011fer \u00f6nlemlerdir (65). \u0130nsanda kullan\u0131labilecek bir a\u015f\u0131 hen\u00fcz bulunmamaktad\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h3 class=\"p7\">Temas Sonras\u0131 Profilaksi<\/h3>\n<p class=\"p3\">Etik sebepler, <i>Brucella<\/i> temas\u0131na neden olan olaylar\u0131n \u00e7e\u015fitlili\u011fi, ger\u00e7ek riskin tan\u0131mlanmas\u0131n\u0131n g\u00fc\u00e7l\u00fc\u011f\u00fc, her salg\u0131nda az say\u0131da ki\u015finin bulunmas\u0131 nedeniyle, riskli \u00e7al\u0131\u015fanlarda, temas sonras\u0131 profilaksinin etkinli\u011fini de\u011ferlendiren kontroll\u00fc \u00e7al\u0131\u015fma bulunmamaktad\u0131r. Ancak anekdotal veriler, temas sonras\u0131 profilaksinin, klinik hastal\u0131k geli\u015fme riskini azaltabilece\u011fini g\u00f6stermektedir (66).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p14\"><strong><em>Bruselloz Olan Hayvanla veya \u00dcr\u00fcnleriyle Temas<\/em><\/strong><\/p>\n<p class=\"p3\">Hasta bruselloz semptomlar\u0131 a\u00e7\u0131s\u0131ndan bilgilendirilir ve izlenir; insan brusellozu semptomlar\u0131 olmas\u0131 halinde uygun \u00f6rnekler al\u0131narak test yap\u0131l\u0131r. <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p14\"><strong><em>Hayvan A\u015f\u0131s\u0131yla Temas<\/em><\/strong><\/p>\n<p class=\"p3\">Hayvanlarda kullan\u0131lan <i>Brucella <\/i>a\u015f\u0131lar\u0131 canl\u0131 bakteri i\u00e7erir ve temas halinde hastal\u0131\u011f\u0131 bula\u015ft\u0131rma riski ta\u015f\u0131r. Bu a\u015f\u0131lar\u0131 uygulayan veterinerlerde kazayla inok\u00fclasyon s\u0131k g\u00f6r\u00fclmektedir. A\u015f\u0131 olarak s\u0131\u011f\u0131rlarda <i>B. abortus<\/i> 19 veya RB51 su\u015fu, koyun ve ke\u00e7ilerde ise <i>B. melitensis<\/i> Rev 1 su\u015fu kullan\u0131lmaktad\u0131r. Bu a\u015f\u0131lar\u0131n kazayla inok\u00fclasyonunda bruselloz bula\u015fma riski, \u00f6zellikle miktar azsa \u00e7ok y\u00fcksek de\u011fildir, ancak potansiyel bula\u015fma riski nedeniyle bu \u015fekilde temas\u0131 olan ki\u015filere de h\u0131zla temas sonras\u0131 profilaksi (PEP) ba\u015flanmal\u0131d\u0131r. RB51 su\u015fu RIF\u2019e diren\u00e7li oldu\u011fu i\u00e7in PEP\u2019te bu ila\u00e7 kullan\u0131lmamal\u0131d\u0131r (67). Bu durumda PEP olarak DOX 2X100 mg\/g\u00fcn, TMP-SMX 160\/800 tb 2X1\/g\u00fcn, 21 g\u00fcn kullan\u0131labilir (65,66,68). D\u00fcnya Sa\u011fl\u0131k \u00d6rg\u00fct\u00fc, DOX\u2019u tek ba\u015f\u0131na 42 g\u00fcn \u00f6nermektedir (27). <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Bu a\u015f\u0131lar\u0131n g\u00f6ze s\u0131\u00e7ramas\u0131 halinde (konjunktival inok\u00fclasyon) bruselloz bula\u015fma riski daha y\u00fcksektir.<span class=\"Apple-converted-space\">\u00a0 <\/span>Bu nedenle bu t\u00fcr temaslarda lokal g\u00f6z bak\u0131m\u0131 ve bir veya iki ila\u00e7la 6 haftal\u0131k tam tedavi \u00f6nerilmektedir. <i>Brucella<\/i> RB51 su\u015fu, hayvanlarda s\u00fcte ge\u00e7ebilmesi nedeniyle insanlara bu yolla da bula\u015farak infeksiyonlara neden olabilmektedir. RB51 infeksiyonunu tespit etmek i\u00e7in mevcut bir serolojik test yoktur. A\u015f\u0131yla temas etmi\u015f semptomatik bireyler i\u00e7in kan k\u00fclt\u00fcr\u00fc \u00f6nerilir (68).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p14\"><strong><em>Laboratuvar Materyalleriyle Temas<\/em><\/strong><\/p>\n<p class=\"p3\">Kontamine materyalle temas\u0131 olacak ki\u015filer, maruziyet riski a\u00e7\u0131s\u0131ndan de\u011ferlendirilerek; \u201cy\u00fcksek risk\u201d, \u201cd\u00fc\u015f\u00fck risk\u201d ve \u201c\u00e7ok d\u00fc\u015f\u00fck risk\u201d \u015feklinde grupland\u0131r\u0131lmal\u0131d\u0131r. Y\u00fcksek riskli temasta m\u00fcmk\u00fcn olan en k\u0131sa s\u00fcrede antimikrobiyal profilaksiye ba\u015flanmal\u0131d\u0131r. Bununla birlikte profilaksi, temastan 24 hafta sonras\u0131na kadar ba\u015flanabilir. D\u00fc\u015f\u00fck riskli temasta ise, semptom ve serolojik takip yap\u0131larak serokonversiyon olu\u015ftu\u011funda tedavi verilmesi \u015feklinde bir yakla\u015f\u0131m s\u00f6z konusudur. Ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131 bask\u0131lanm\u0131\u015f bireylerde ve gebelerde profilaksi verilebilir.<span class=\"Apple-converted-space\">\u00a0 <\/span>D\u00fc\u015f\u00fck riskli temas varl\u0131\u011f\u0131nda sa\u011fl\u0131k \u00e7al\u0131\u015fan\u0131 ile birlikte tart\u0131\u015f\u0131larak karar verilmelidir (28,65,66,69).<\/p>\n<p class=\"p3\">Y\u00fcksek riskli temas; bakteri k\u00fclt\u00fcr\u00fcn\u00fcn koklanmas\u0131, direkt olarak deri ile temas, a\u011f\u0131zla pipetleme, inokulasyon, g\u00f6z, burun veya a\u011f\u0131za s\u0131\u00e7ramas\u0131 gibi \u00e7al\u0131\u015fan\u0131n direkt temas\u0131, a\u00e7\u0131k tezgahta <i>Brucella<\/i> \u00fcreyen k\u00fclt\u00fcr ile \u00e7al\u0131\u015fmak (BSL-3 alanlar\u0131 d\u0131\u015f\u0131nda \u00e7al\u0131\u015fmak) veya <i>Brucella<\/i> \u00e7al\u0131\u015fma alan\u0131na 1.5 m veya daha yak\u0131n bulunmak, <i>Brucella<\/i> izolat\u0131 ile yap\u0131lan aerosol olu\u015fturan herhangi bir i\u015flem s\u0131ras\u0131nda laboratuvarda bulunmak, inhale etmek (\u00f6rne\u011fin vorteksleme veya katalaz testi) ve amniyotik s\u0131v\u0131, plasenta gibi \u00fcreme materyalleri ile \u00e7al\u0131\u015fmak olarak tan\u0131mlanm\u0131\u015ft\u0131r (28).<\/p>\n<p class=\"p3\"><i>Brucella<\/i> su\u015fu pozitif kan k\u00fclt\u00fcr\u00fc \u015fi\u015fesi veya amniyotik s\u0131v\u0131, plasenta gibi \u00fcreme sistemi materyalleri ile \u00e7al\u0131\u015fan birinden 1.5 m\u2019den daha uzak mesafede bulunmak, aerosol olu\u015fturmayan i\u015flemler s\u0131ras\u0131nda a\u00e7\u0131k bir bankta \u00e7al\u0131\u015fmak d\u00fc\u015f\u00fck riskli temas olarak tan\u0131mlanmaktad\u0131r (28).<\/p>\n<p class=\"p3\">Riskli i\u015flemlerin, uygun ki\u015fisel koruyucu ekipman (\u00f6rn. eldiven, \u00f6nl\u00fck, g\u00f6z korumas\u0131) ile sertifikal\u0131 S\u0131n\u0131f II biyog\u00fcvenlik kabininde ger\u00e7ekle\u015ftirilmesi ve kan, serum, beyin omurilik s\u0131v\u0131s\u0131 gibi rutin bir klinik numunenin sertifikal\u0131 bir S\u0131n\u0131f II biyog\u00fcvenlik kabininde, uygun ki\u015fisel koruyucu ekipman (\u00f6rn. eldiven, \u00f6nl\u00fck, g\u00f6z korumas\u0131) kullan\u0131larak \u00e7al\u0131\u015f\u0131lmas\u0131 minimum (\u00e7ok d\u00fc\u015f\u00fck) riskli temas olarak kabul edilmektedir. Bu durumda herhangi bir takip \u00f6nerilmemektedir (28).<\/p>\n<div id=\"attachment_26989\" style=\"width: 2193px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T4.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-26989\" class=\"size-full wp-image-26989\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T4.png\" alt=\"\" width=\"2183\" height=\"800\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T4.png 2183w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T4-390x143.png 390w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T4-810x297.png 810w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/06\/KLM-4576-T4-768x281.png 768w\" sizes=\"auto, (max-width: 2183px) 100vw, 2183px\" \/><\/a><p id=\"caption-attachment-26989\" class=\"wp-caption-text\"><strong>Tablo 4.<\/strong> Bruselloz Olgular\u0131nda Tedavi \u00d6nerileri<\/p><\/div>\n<p class=\"p3\">Temas sonras\u0131 profilaksi i\u00e7in DOX 2X100 mg\/g\u00fcn, RIF 1X600mg\/g\u00fcn 21 g\u00fcn boyunca kullan\u0131lmal\u0131d\u0131r (28, 68). Baz\u0131 yazarlar 21 g\u00fcnl\u00fck DOX tedavisinin de tek ba\u015f\u0131na yeterli olabilece\u011fini bildirmektedir (65). Temas eden ki\u015filer 6 ay boyunca, haftal\u0131k olarak semptom geli\u015fimi ve temas sonras\u0131nda bazal, 6, 12, 18 ve 24. haftalarda olmak \u00fczere serolojik testlerle izlenmelidir (28, 69).<span class=\"Apple-converted-space\">\u00a0 <\/span>Profilaksi \u00f6nerileri Tablo 4\u2019te \u00f6zetlenmi\u015ftir.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h2 class=\"p1\">PICO SORULARI, \u00d6NER\u0130LER VE \u00d6NER\u0130LER\u0130 DESTEKLEYEN KANITLARIN \u00d6ZET\u0130<\/h2>\n<h4 class=\"p2\">1- Brusellozdan ku\u015fkulan\u0131lan hastalarda Rose Bengal testinin tan\u0131daki yeri nedir?<\/h4>\n<p class=\"p3\"><b>\u00d6neri: <\/b>Rose Bengal (RB) testinin bruselloz tan\u0131s\u0131nda duyarl\u0131l\u0131\u011f\u0131 y\u00fcksektir. Temas \u00f6yk\u00fcs\u00fc ve uyumlu semptomlar\u0131 olan hastalarda h\u0131zl\u0131 tan\u0131 testi olarak \u00f6nerilir (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>). Yap\u0131lan meta-analizlerde \u00f6zg\u00fcll\u00fc\u011f\u00fc de y\u00fcksek bulunmakla birlikte kontrol gruplar\u0131 uygun olmad\u0131\u011f\u0131 i\u00e7in, mevcut veriler bruselloz tan\u0131s\u0131nda tek ba\u015f\u0131na kullan\u0131lmas\u0131 konusunda yeterli de\u011fildir. Antikor taramaya y\u00f6nelik bir test olmas\u0131 nedeniyle hastal\u0131\u011f\u0131n erken d\u00f6nemlerinde yalanc\u0131 negatiflik olabilece\u011finin de ak\u0131lda tutulmas\u0131 \u00f6nerilir (<i>\u00c7ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> \u00d6neri ile ilgili kan\u0131tlar, bruselloz tan\u0131s\u0131nda RB testinin duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fcn\u00fcn ara\u015ft\u0131r\u0131ld\u0131\u011f\u0131 sekiz kesitsel \u00e7al\u0131\u015fman\u0131n meta-analizine dayanmaktad\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>Bu \u00e7al\u0131\u015fmalar\u0131n be\u015finde (70-74) referans test olarak k\u00fclt\u00fcr pozitifli\u011fi al\u0131n\u0131rken, birinde (75) k\u00fclt\u00fcr ve\/veya STA pozitifli\u011fi, birinde (76) k\u00fclt\u00fcr ve\/veya STA pozitifli\u011fi veya titre art\u0131\u015f\u0131, birinde (77) ise yaln\u0131z STA pozitifli\u011fi al\u0131nm\u0131\u015ft\u0131r. Meta-analizine t\u00fcm \u00e7al\u0131\u015fmalar (n=3347) dahil edildi\u011finde, RB testinin havuz duyarl\u0131l\u0131\u011f\u0131 %99 (%95 GA=%90-99) \u00f6zg\u00fcll\u00fc\u011f\u00fc ise %96 (%95 GA=%80-99) bulunmu\u015ftur. Yaln\u0131z k\u00fclt\u00fcr\u00fcn referans al\u0131nd\u0131\u011f\u0131 \u00e7al\u0131\u015fmalar (n=2752) esas al\u0131nd\u0131\u011f\u0131nda ise havuz duyarl\u0131l\u0131k %99 (%95 GA=%47-99); \u00f6zg\u00fcll\u00fck ise %94 (%95 GA=%71-99) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Andriopoulus ve arkada\u015flar\u0131n\u0131n (70) 2015 y\u0131l\u0131nda yay\u0131mlanan \u00e7al\u0131\u015fmas\u0131nda, 2000-2010 y\u0131llar\u0131 aras\u0131nda Sparta Hastanesi\u2019nde takip edilen 83 akut bruselloz hastas\u0131 i\u00e7inde kan k\u00fclt\u00fcr\u00fc pozitifli\u011fi olan 65 hasta \u00e7al\u0131\u015fma grubu olarak al\u0131nm\u0131\u015ft\u0131r. Ayn\u0131 hasta grubu i\u00e7erisinden 2013 y\u0131l\u0131nda kontrol edilen tamamen sa\u011fl\u0131kl\u0131 olan 72 birey kontrol grubu olarak al\u0131nm\u0131\u015ft\u0131r. Rose Bengal testinde <i>B. abortus<\/i> antijeni ve bir otomatize k\u00fclt\u00fcr sistemi (bioM\u00e9rieux, Fransa) kullan\u0131lm\u0131\u015ft\u0131r. Testin duyarl\u0131l\u0131\u011f\u0131 %100 (%95 GA=%94-100), \u00f6zg\u00fcll\u00fc\u011f\u00fc %88 (%95 GA=%78-94) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">\u00c7ift\u00e7i ve arkada\u015flar\u0131n\u0131n (71) 2005\u2019te yay\u0131mlanan \u00e7al\u0131\u015fmas\u0131nda, Eyl\u00fcl 2001-Eyl\u00fcl 2003 tarihleri aras\u0131nda Akdeniz \u00dcniversitesi T\u0131p Fak\u00fcltesi Hastanesi\u2019ndeki 77 bruselloz \u015f\u00fcpheli olgu i\u00e7in kan k\u00fclt\u00fcr\u00fc pozitifli\u011fi olan 35 olgu \u00e7al\u0131\u015fma grubu, kalan 42 olgu ise kontrol grubu olarak al\u0131nm\u0131\u015ft\u0131r. Rose Bengal testi i\u00e7in <i>B. abortus<\/i> S99 su\u015fundan haz\u0131rlanan ticari antijen (Spinreact, \u0130spanya) kullan\u0131lm\u0131\u015ft\u0131r. Testin duyarl\u0131l\u0131\u011f\u0131 %100 (%95 GA=%90-100), \u00f6zg\u00fcll\u00fc\u011f\u00fc %45 (%95 GA=%30-61) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Diaz ve arkada\u015flar\u0131n\u0131n \u00e7al\u0131\u015fmas\u0131 (72), 1975-2001 y\u0131llar\u0131 aras\u0131nda Barselona\u2019daki yedi merkezde yap\u0131lm\u0131\u015ft\u0131r. \u00c7al\u0131\u015fmada 208 k\u00fclt\u00fcr pozitif olgu<br \/>\n(<i>B. melitensis<\/i>) \u00e7al\u0131\u015fma grubu olarak al\u0131n\u0131rken, brusellozla ili\u015fkili semptomu olmay\u0131p ba\u015fka infeksiyon \u015f\u00fcphesi olan 1559 ki\u015fi birinci kontrol grubu ve asemptomatik olup yak\u0131n hayvan temas\u0131 olan ya da canl\u0131 hayvan a\u015f\u0131s\u0131 batan 20 ki\u015fi ikinci kontrol grubu olarak al\u0131nm\u0131\u015ft\u0131r. Rose Bengal testi i\u00e7in 30 \u00b5l serum ile <i>Brucella<\/i> antijeni (\u201cVeterinary Laboratory Agency\u201d, \u0130ngiltere) kar\u0131\u015ft\u0131r\u0131larak 8 dk ink\u00fcbe edilmi\u015ftir. Testin duyarl\u0131l\u0131\u011f\u0131 %100 (%95 GA=%98-100), \u00f6zg\u00fcll\u00fc\u011f\u00fc %99 (%95 GA=%98-99) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Mert ve arkada\u015flar\u0131n\u0131n (73) 2003\u2019te yay\u0131mlanan \u00e7al\u0131\u015fmas\u0131nda, \u0130stanbul \u00dcniversitesi, Cerrahpa\u015fa T\u0131p Fak\u00fcltesi Hastanesi\u2019nde son 20 y\u0131ll\u0131k d\u00f6nemde takipli 30 k\u00fclt\u00fcr pozitif hasta \u00e7al\u0131\u015fma grubu olarak al\u0131n\u0131rken; brusellozu taklit eden ba\u015fka hastal\u0131\u011f\u0131 olan 280 hasta (20 miliyer t\u00fcberk\u00fcloz, 33 s\u0131tma, 20 tifoid ate\u015f, 20 eri\u015fkin \u201cstill\u201d hastal\u0131\u011f\u0131, 47 sistemik lupus eritematozus, 50 romatoid artrit, 27 sarkoidoz, 63 lenfoma) kontrol grubu olarak al\u0131nm\u0131\u015ft\u0131r. Agl\u00fctinasyon testlerinde <i>B. abortus<\/i> S.99 su\u015fu (Pendik Veteriner Ara\u015ft\u0131rma Laboratuvar\u0131, \u0130stanbul, T\u00fcrkiye) kullan\u0131lm\u0131\u015f olup testler k\u00f6r olarak yap\u0131lm\u0131\u015ft\u0131r. Testin duyarl\u0131l\u0131\u011f\u0131 %100 (%95 GA=%88-100), \u00f6zg\u00fcll\u00fc\u011f\u00fc %100 (%95 GA=%99-100) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Purwar ve arkada\u015flar\u0131n\u0131n (74) \u00e7al\u0131\u015fmas\u0131nda, Ocak 2004-Temmuz 2005 tarihleri aras\u0131nda Hindistan\u2019\u0131n Karnataka eyaletinde bir hastaneye akut nedeni bilinmeyen ate\u015f yak\u0131nmas\u0131 ile ba\u015fvuran 400 hasta i\u00e7inde 20 k\u00fclt\u00fcr pozitif olgu \u00e7al\u0131\u015fma grubu olarak al\u0131n\u0131rken kalan 380 hasta kontrol grubu olarak al\u0131nm\u0131\u015ft\u0131r. Rose Bengal antijeni Hindistan Veterinerlik Ara\u015ft\u0131rma Enstit\u00fcs\u00fc, Biyolojik \u00dcr\u00fcnler B\u00f6l\u00fcm\u00fc\u2019nden temin edilmi\u015ftir. K\u00fclt\u00fcr i\u00e7in 5-10 ml kan \u00f6rne\u011fi beyin-kalp inf\u00fczyonu agara Castaneda y\u00f6ntemi ile inok\u00fcle edilmi\u015f ve 37 \u00b0C\u2019de d\u00f6rt haftaya kadar veya \u00fcremenin ortaya \u00e7\u0131kt\u0131\u011f\u0131 zamana kadar (hangisi daha \u00f6nceyse) ink\u00fcbe edilmi\u015ftir. Testin duyarl\u0131l\u0131\u011f\u0131 %100 (%95 GA=%83-100), \u00f6zg\u00fcll\u00fc\u011f\u00fc %96 (%95 GA=%94-98) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">S\u0131rmatel ve arkada\u015flar\u0131n\u0131n (75) \u00e7al\u0131\u015fmas\u0131nda, 1992-1995 y\u0131llar\u0131 aras\u0131nda Gaziantep \u00dcniversitesi T\u0131p Fak\u00fcltesi Hastanesi\u2019nde bruselloz tan\u0131s\u0131 ile takip edilen 184 hasta \u00e7al\u0131\u015fma grubu olarak al\u0131n\u0131rken 20 sa\u011fl\u0131kl\u0131 kan donor\u00fc kontrol grubu olarak al\u0131nm\u0131\u015ft\u0131r. Testin duyarl\u0131l\u0131\u011f\u0131 %68 (%95 GA=%61-75), \u00f6zg\u00fcll\u00fc\u011f\u00fc %70 (%95 GA=%46-88) bulunmu\u015ftur. Ayn\u0131 \u00e7al\u0131\u015fman\u0131n alt analizi yap\u0131larak yaln\u0131z k\u00fclt\u00fcr pozitif olan 20 olgu ele al\u0131nd\u0131\u011f\u0131nda ise testin duyarl\u0131l\u0131\u011f\u0131 %90 (%95 GA=%70-99), \u00f6zg\u00fcll\u00fc\u011f\u00fc %70 (%95 GA=%46-88) olarak bulunmu\u015ftur.<\/p>\n<p class=\"p3\"><span class=\"s2\">Vrioni ve arkada\u015flar\u0131n\u0131n (76) \u00e7al\u0131\u015fmas\u0131nda, Ocak 2000-Aral\u0131k 2002 aras\u0131 Yunanistan, Ioannina \u00dcniversite Hastanesi\u2019nde takipli 243 akut bruselloz hastas\u0131 \u00e7al\u0131\u015fma grubu olarak al\u0131n\u0131rken 50 sa\u011fl\u0131kl\u0131 kan donor\u00fc kontrol grubu olarak al\u0131nm\u0131\u015ft\u0131r. Kan k\u00fclt\u00fcr\u00fc i\u00e7in BacT\/Alert sisteminde (bioM\u00e9rieux, Fransa) 10 g\u00fcn s\u00fcreyle ink\u00fcbe edilmi\u015f, \u00fcreme olmazsa 10 g\u00fcn daha uzat\u0131lm\u0131\u015f ve <i>Brucella<\/i> agara (Becton Dickinson, ABD) 10. ve 20. g\u00fcnlerde k\u00f6r alt k\u00fclt\u00fcrler ekilmi\u015ftir. Bu alt k\u00fclt\u00fcrler, \u00fc\u00e7 g\u00fcn boyunca %5 ila %10 CO2 atmosferde 37\u00b0C\u2019de ink\u00fcbe edilmi\u015ftir. Rose Bengal testinin duyarl\u0131l\u0131\u011f\u0131 %96 (%95 GA=%93-98), \u00f6zg\u00fcll\u00fc\u011f\u00fc %100 (%95 GA=%93-100) bulunmu\u015ftur.<\/span><\/p>\n<p class=\"p3\">El-Hossain Aly Reda ve arkada\u015flar\u0131n\u0131n (77) Kahire\u2019de ger\u00e7ekle\u015ftirdi\u011fi \u00e7al\u0131\u015fmada, Kas\u0131m 2015-May\u0131s 2016 tarihleri aras\u0131nda klinik olarak bruselloz \u015f\u00fcphesi olan 100 serum \u00f6rne\u011fi de\u011ferlendirilmi\u015f ve STA pozitifli\u011fi olan 95 olgu \u00e7al\u0131\u015fma grubu olarak al\u0131nm\u0131\u015ft\u0131r. Rose Bengal testinde BioMed-RB kullan\u0131larak 50 \u00b5l hasta serumu ile 50 \u00b5l \u00f6l\u00fc <i>B. abortus<\/i> antijeni lam \u00fczerinde kar\u0131\u015ft\u0131r\u0131lm\u0131\u015f 4 dk ink\u00fcbasyon sonras\u0131 agl\u00fctinasyon olmas\u0131 pozitif olarak yorumlanm\u0131\u015ft\u0131r. STA testinde 1 damla (50 \u00b5l) BioMed-Brucel- <i>Abortus<\/i> \/ <i>Melitensis<\/i> antijeni seri dil\u00fce edilmi\u015f, 1 ml\u2019lik serum \u00f6rnekleri (1:20-1:1280) ile kar\u0131\u015ft\u0131r\u0131lm\u0131\u015f ve 37\u00b0C\u2019de 24 saat ink\u00fcbe edilmi\u015ftir. Rose Bengal testinin duyarl\u0131l\u0131\u011f\u0131 %96 (%95 GA=%90-99), \u00f6zg\u00fcll\u00fc\u011f\u00fc %100 (%95 GA=%48-100) bulunmu\u015ftur. (Bkz. Ek \u015eekil 8-10, Ek Tablo 1-3)<\/p>\n<p class=\"p3\"><strong>\u00d6neri Gerek\u00e7esi:<\/strong> Rose Bengal testi, y\u00fcksek duyarl\u0131l\u0131k d\u00fczeyi, kolay ula\u015f\u0131labilir olmas\u0131 ve h\u0131zl\u0131 sonu\u00e7 vermesi nedenleri ile bruselloz tan\u0131 algoritmas\u0131nda ilk uygulanacak testtir.<\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> De\u011ferlendirilen \u00e7al\u0131\u015fmalar\u0131n hemen hemen tamam\u0131nda, testin yap\u0131ld\u0131\u011f\u0131 grup bruselloz olma olas\u0131l\u0131\u011f\u0131 y\u00fcksek olan hastalardan (klinik bulgular\u0131 uyumlu ve \u015f\u00fcpheli temas \u00f6yk\u00fcleri olmas\u0131 nedeni ile) ve kontrol grubu da bruselloz olmad\u0131\u011f\u0131 bilinen sa\u011fl\u0131kl\u0131 ki\u015filer ya da kan don\u00f6rlerinden olu\u015fmaktad\u0131r. \u00c7al\u0131\u015fmalar\u0131n \u00e7o\u011funda \u00f6rneklem b\u00fcy\u00fckl\u00fckleri belirsizdir. Rose Bengal testi ile bruselloz tan\u0131s\u0131n\u0131n d\u0131\u015flanabilmesi i\u00e7in, hastal\u0131\u011f\u0131n endemik oldu\u011fu b\u00f6lgelerde yap\u0131lacak, yeterli \u00f6rneklem b\u00fcy\u00fckl\u00fc\u011f\u00fcne sahip, yaln\u0131z bruselloz \u015f\u00fcpheli hastalar\u0131n dahil edildi\u011fi, prospektif saha \u00e7al\u0131\u015fmalar\u0131na gereksinim vard\u0131r. <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h4 class=\"p2\">2- Brusellozdan ku\u015fkulan\u0131lan hastalarda Wright standart t\u00fcp agl\u00fctinasyon testinin tan\u0131daki yeri nedir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Brusellozdan ku\u015fkulan\u0131lan hastalarda Wright standart t\u00fcp agl\u00fctinasyon (STA) testinin \u22651:160 titrasyonda pozitifli\u011finin, bruselloz tan\u0131s\u0131 i\u00e7in duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fc y\u00fcksek bulunmu\u015ftur. Erken tedavi ba\u015flanmas\u0131n\u0131n gerekli oldu\u011fu durumlarda h\u0131zl\u0131 tan\u0131da veya k\u00fclt\u00fcr\u00fcn yap\u0131lamad\u0131\u011f\u0131 durumlarda tan\u0131da Wright STA testi kullan\u0131labilir. Brusellozdan ku\u015fkulan\u0131lan hastalarda RB testi pozitif saptand\u0131\u011f\u0131nda da tan\u0131n\u0131n, daha \u00f6zg\u00fcl olmas\u0131 nedeniyle Wright STA testi ile do\u011frulanmas\u0131 \u00f6nerilir (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<\/p>\n<p class=\"p3\">Brusella endokarditi olan hastalarda, Wright STA\u2019n\u0131n \u22651:1280 titrede pozitif olmas\u0131 mortalite ile ili\u015fkili bulunmu\u015ftur. Dolay\u0131s\u0131yla bu hasta grubunda prognozu \u00f6ng\u00f6rmek i\u00e7in Wright STA testinin kullan\u0131m\u0131 da d\u00fc\u015f\u00fcn\u00fclebilir (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, zay\u0131f \u00f6neri<\/i>).<\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti: <\/strong>\u00d6neri ile ilgili kan\u0131tlar, bruselloz tan\u0131s\u0131nda k\u00fclt\u00fcr\u00fcn referans test al\u0131narak, STA testinin duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fcn\u00fcn ara\u015ft\u0131r\u0131ld\u0131\u011f\u0131 dokuz kesitsel \u00e7al\u0131\u015fman\u0131n meta-analizine dayanmaktad\u0131r. Bu \u00e7al\u0131\u015fmalar\u0131n meta-analizi sonucu (n=3015) STA testinin havuz duyarl\u0131l\u0131\u011f\u0131 %96 (%95 GA=%90-98); \u00f6zg\u00fcll\u00fc\u011f\u00fc %99 (%95 GA=%98-99); pozitif olas\u0131l\u0131k oran\u0131 130.2 (%95 GA=50.81-333.61); negatif olas\u0131l\u0131k oran\u0131 ise 0.03 (%95 GA= 0.01- 0.1) bulunmu\u015ftur (Bkz. Ek Bruselloz tan\u0131s\u0131).<\/p>\n<p class=\"p3\">Andriopoulus ve arkada\u015flar\u0131n\u0131n (70) \u00e7al\u0131\u015fmas\u0131nda, STA testinde <i>B. abortus<\/i> antijeni ile serum \u00f6rnekleri 1:40-1:3200 aras\u0131 dil\u00fcsyonlarda kar\u0131\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. Otomatize k\u00fclt\u00fcr sistemi (bioM\u00e9rieux, Fransa) kullan\u0131lm\u0131\u015f. Testin duyarl\u0131l\u0131\u011f\u0131 %100 (%95 GA=%94-100), \u00f6zg\u00fcll\u00fc\u011f\u00fc %89 (%95 GA=%79-95) bulunmu\u015ftur.<\/p>\n<p class=\"p3\"><span class=\"s2\">Arabac\u0131 ve Oldacay\u2019\u0131n (78) \u00e7al\u0131\u015fmas\u0131nda, 2009 y\u0131l\u0131 boyunca \u00c7anakkale Devlet Hastanesi\u2019nde takipli seroloji ve k\u00fclt\u00fcr pozitifli\u011fi ile tan\u0131 konulan 131 akut bruselloz hastas\u0131 \u00e7al\u0131\u015fma grubuna al\u0131n\u0131rken 105 sa\u011fl\u0131kl\u0131 kan don\u00f6r\u00fc kontrol grubuna al\u0131nm\u0131\u015ft\u0131r. Standart t\u00fcp agl\u00fctinasyon testinde <i>B. abortus <\/i>antijeni (Refik Saydam H\u0131fz\u0131ss\u0131hha Merkezi Ba\u015fkanl\u0131\u011f\u0131, Ankara, T\u00fcrkiye) ile serum \u00f6rnekleri 1:40-1:5160 aras\u0131 dil\u00fcsyonlarda kar\u0131\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. Otomatize kan k\u00fclt\u00fcr\u00fc sistemi (VERSA-TREK, ABD) kullan\u0131lm\u0131\u015ft\u0131r. Be\u015f g\u00fcn i\u00e7inde \u00fcreme olmayan \u00f6rneklerde ink\u00fcbasyon 30 g\u00fcne uzat\u0131lm\u0131\u015f ve yedi g\u00fcn sonra <i>Brucella<\/i> agara (Beckton Dickinson, ABD) k\u00f6r alt k\u00fclt\u00fcrler ekilmi\u015ftir. Bruselloz tan\u0131l\u0131 131 olgu aras\u0131nda yaln\u0131z k\u00fclt\u00fcr pozitif olan 9 olgu meta-analizine dahil edilerek STA testinin duyarl\u0131l\u0131\u011f\u0131 %100 (%95 <\/span>GA=%66-100), \u00f6zg\u00fcll\u00fc\u011f\u00fc %99 (%95 GA=%95-100) olarak hesaplanm\u0131\u015ft\u0131r.<\/p>\n<p class=\"p3\">\u00c7eken ve arkada\u015flar\u0131n\u0131n (79) Ocak-Haziran 2007 d\u00f6neminde Ankara\u2019da yapt\u0131klar\u0131 \u00e7al\u0131\u015fmada, 35 akut bruselloz olgusu i\u00e7inde k\u00fclt\u00fcr pozitif 16 olgu \u00e7al\u0131\u015fma grubu olarak belirlenmi\u015ftir. Kontrol grubu ise hastaneye ba\u015fka sebeplerden ba\u015fvuran klinik olarak bruselloz d\u00fc\u015f\u00fcn\u00fclmeyen, STA titresi negatif olan g\u00f6n\u00fcll\u00fc ki\u015filerden olu\u015fturulmu\u015ftur. Standart t\u00fcp agl\u00fctinasyon testi i\u00e7in <i>B. abortus<\/i> S99 su\u015fu antijeni (Refik Saydam H\u0131fz\u0131ss\u0131hha Merkezi Ba\u015fkanl\u0131\u011f\u0131, Ankara, T\u00fcrkiye) kullan\u0131lm\u0131\u015ft\u0131r. Kan k\u00fclt\u00fcrleri Bactec 9050 (Becton Dickinson, ABD) otomatize sistemi ile 30 g\u00fcn s\u00fcre ile ink\u00fcbe edilmi\u015ftir. \u0130nk\u00fcbasyonun 10, 20 ve 30. g\u00fcnlerinde \u00fcremeyen \u00f6rneklerden k\u00f6r pasajlar yap\u0131lm\u0131\u015ft\u0131r. Testin duyarl\u0131l\u0131\u011f\u0131 %94 (%95 GA=%70-100), \u00f6zg\u00fcll\u00fc\u011f\u00fc %100 (%95 GA=%83-100) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Diaz ve arkada\u015flar\u0131n\u0131n (72) yukar\u0131da s\u00f6z edilen \u00e7al\u0131\u015fmas\u0131nda, STA testi mikrotitre plaklar\u0131nda ger\u00e7ekle\u015ftirilmi\u015ftir. Testin duyarl\u0131l\u0131\u011f\u0131 %89 (%95 GA=%84-93), \u00f6zg\u00fcll\u00fc\u011f\u00fc %100 (%95 GA=%99-100) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Ertek ve arkada\u015flar\u0131n\u0131n (80) Atat\u00fcrk \u00dcniversitesi T\u0131p Fak\u00fcltesi Hastanesi\u2019nde y\u00fcr\u00fctt\u00fckleri \u00e7al\u0131\u015fmada, 32 k\u00fclt\u00fcr pozitif olgu \u00e7al\u0131\u015fma grubu ve 20 sa\u011fl\u0131kl\u0131 birey kontrol grubu olarak belirlenmi\u015ftir. Standart t\u00fcp agl\u00fctinasyon testi i\u00e7in <i>B. abortus<\/i> antijeni (Pendik Veteriner Kontrol Enstit\u00fcs\u00fc, \u0130stanbul, T\u00fcrkiye) kullan\u0131lm\u0131\u015f ve serum \u00f6rnekleri 1:20\u2019den ba\u015flayarak dil\u00fce edilmi\u015ftir. K\u00fclt\u00fcr i\u00e7in aseptik olarak hastalardan iki kan numunesi (her biri 10 ml) ve bir kemik ili\u011fi numunesi (sternal aspirat, 1 ml) al\u0131nm\u0131\u015f ve BACTEC 9240 sisteminde (Becton-Dickinson, ABD) 21 g\u00fcn s\u00fcreyle ink\u00fcbe edilmi\u015ftir. Testin duyarl\u0131l\u0131\u011f\u0131 %94 (%95 GA=%79-99), \u00f6zg\u00fcll\u00fc\u011f\u00fc %100 (%95 GA=%83-100) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Memish ve arkada\u015flar\u0131n\u0131n (81) \u00e7al\u0131\u015fmas\u0131nda, Ekim 1999-Ekim 2000 aras\u0131nda, semptomatik k\u00fclt\u00fcr pozitif 68 olgu ve 70 sa\u011fl\u0131kl\u0131 g\u00f6n\u00fcll\u00fc hasta de\u011ferlendirmeye al\u0131nm\u0131\u015ft\u0131r. Standart t\u00fcp agl\u00fctinasyon testi i\u00e7in <i>B. abortus<\/i> ve <i>B. melitensis<\/i> antijenleri 10<sup>10<\/sup> mikroorganizma\/ml i\u00e7eren <i>B. abortus<\/i> SS14 ve <i>B. melitensis<\/i> SS15 s\u00fcspansiyonlar\u0131 (Wellcome Diagnostics, \u0130ngiltere) kullan\u0131larak bir mikrotitre aglutinasyon prosed\u00fcr\u00fc ile \u00f6l\u00e7\u00fclm\u00fc\u015f, prezon fenomenini \u00f6nlemek i\u00e7in serumlar rutin olarak 1:80\u2019den 1:20 480\u2019e seyreltilmi\u015ftir. K\u00fclt\u00fcr i\u00e7in hastalardan iki kan numunesi (her biri 5-10 ml) al\u0131nm\u0131\u015f ve BACTEC 9240 sisteminde (Becton-Dickinson, ABD) 7 g\u00fcn s\u00fcreyle ink\u00fcbe edilmi\u015ftir. Testin duyarl\u0131l\u0131\u011f\u0131 %96 (%95 GA=%88-99), \u00f6zg\u00fcll\u00fc\u011f\u00fc %100 (%95 GA=%95-100) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Mert ve arkada\u015flar\u0131n\u0131n (73) yukar\u0131da a\u00e7\u0131kland\u0131\u011f\u0131 gibi ger\u00e7ekle\u015ftirilen \u00e7al\u0131\u015fmas\u0131nda, STA testinde <i>B. abortus<\/i> S.99 su\u015fu (Pendik Veteriner Kontrol Enstit\u00fcs\u00fc, \u0130stanbul, T\u00fcrkiye) kullan\u0131lm\u0131\u015f, testin duyarl\u0131l\u0131\u011f\u0131 %100 (%95 GA=%88-100), \u00f6zg\u00fcll\u00fc\u011f\u00fc %99 (%95 GA=%97-100) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Purwar ve arkada\u015flar\u0131n\u0131n \u00e7al\u0131\u015fmas\u0131nda (74), STA antijeni Hindistan Veterinerlik Ara\u015ft\u0131rma Enstit\u00fcs\u00fc Biyolojik \u00dcr\u00fcnler B\u00f6l\u00fcm\u00fc\u2019nden temin edilmi\u015ftir. Testin duyarl\u0131l\u0131\u011f\u0131 %100 (%95 GA=%83-100), \u00f6zg\u00fcll\u00fc\u011f\u00fc %96 (%95 GA=%94-98) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">S\u0131rmatel ve arkada\u015flar\u0131n\u0131n (75) \u00e7al\u0131\u015fmas\u0131ndaki yaln\u0131z k\u00fclt\u00fcr pozitif olan 20 olgu meta-analizine dahil edildi\u011finde STA testinin duyarl\u0131l\u0131\u011f\u0131 %100 (%95 GA=%84-100) ve \u00f6zg\u00fcll\u00fc\u011f\u00fc %100 (%95 GA=%83-100) bulunmu\u015ftur. (Bkz. Ek \u015eekil 11, 12 ve Ek Tablo 1, 4, 5)<\/p>\n<p class=\"p3\"><strong>\u00d6neri Gerek\u00e7esi:<\/strong> K\u00fclt\u00fcr, bruselloz tan\u0131s\u0131nda alt\u0131n standart tan\u0131 y\u00f6ntemi olmakla birlikte duyarl\u0131l\u0131\u011f\u0131 d\u00fc\u015f\u00fckt\u00fcr. Ayn\u0131 zamanda k\u00fclt\u00fcr sonu\u00e7lar\u0131 ge\u00e7 \u00e7\u0131kmakta ve birinci basamak hatta baz\u0131 ikinci basamak sa\u011fl\u0131k hizmeti veren kurumlarda \u00e7al\u0131\u015f\u0131lamamaktad\u0131r. Standart t\u00fcp agl\u00fctinasyon testi ise olduk\u00e7a duyarl\u0131 ve \u00f6zg\u00fcl bir test olup k\u00fclt\u00fcrden daha kolay uygulanabilmektedir. Ayr\u0131ca bu rehberde brusella endokarditi b\u00f6l\u00fcm\u00fcnde (Bkz. PICO 12) elde edilmi\u015f veriler, tan\u0131 an\u0131nda y\u00fcksek STA testi titrelerinin bulunmas\u0131n\u0131n k\u00f6t\u00fc prognozla ili\u015fkisini desteklemektedir.<\/p>\n<p class=\"p3\"><strong>Bilgi a\u00e7\u0131\u011f\u0131: <\/strong>De\u011ferlendirilen \u00e7al\u0131\u015fmalar\u0131n hemen hemen tamam\u0131nda testin yap\u0131ld\u0131\u011f\u0131 grup bruselloz olma olas\u0131l\u0131\u011f\u0131 y\u00fcksek olan hastalar ve kontrol grubu da bruselloz olmad\u0131\u011f\u0131 bilinen ki\u015filerden olu\u015fmaktad\u0131r. \u00c7al\u0131\u015fmalar\u0131n \u00e7o\u011funda \u00f6rneklem b\u00fcy\u00fckl\u00fckleri belirsizdir. Standart t\u00fcp agl\u00fctinasyon testinin, bruselloz tan\u0131s\u0131nda tek ba\u015f\u0131na g\u00fc\u00e7l\u00fc olarak \u00f6nerilebilmesi i\u00e7in, hastal\u0131\u011f\u0131n endemik oldu\u011fu b\u00f6lgelerde yap\u0131lacak, yeterli \u00f6rneklem b\u00fcy\u00fckl\u00fc\u011f\u00fcne sahip, yaln\u0131z bruselloz \u015f\u00fcpheli hastalar\u0131n dahil edildi\u011fi, prospektif saha \u00e7al\u0131\u015fmalar\u0131na gereksinim vard\u0131r. <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h4 class=\"p2\">3- Brusellozdan ku\u015fkulan\u0131lan hastalarda enzim i\u015faretli imm\u00fcn deney (ELISA) temelli testlerin tan\u0131daki yeri nedir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Brusellozdan ku\u015fkulan\u0131lan, RB testi pozitif hastalarda do\u011frulama amac\u0131yla STA testi yerine ELISA temelli testler de kullan\u0131labilir. Tan\u0131da ELISA temelli testler kullan\u0131lacaksa IgM ve IgG testlerinin birlikte kullan\u0131lmas\u0131 \u00f6nerilir (<i>\u00c7ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri)<\/i>.<\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti: <\/strong>\u00d6neri ile iligili kan\u0131tlar, bruselloz tan\u0131s\u0131nda ELISA testinin duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fcn\u00fcn ara\u015ft\u0131r\u0131ld\u0131\u011f\u0131 sekiz kesitsel \u00e7al\u0131\u015fman\u0131n meta-analizine dayanmaktad\u0131r. Bu \u00e7al\u0131\u015fmalar\u0131n \u00fc\u00e7\u00fcnde (71,80,81) referans test olarak k\u00fclt\u00fcr pozitifli\u011fi al\u0131n\u0131rken, birinde (77) STA pozitifli\u011fi, birinde (82) k\u00fclt\u00fcr ve\/veya STA pozitifli\u011fi, \u00fc\u00e7\u00fcnde ise (75,76,78) k\u00fclt\u00fcr ve\/veya STA pozitifli\u011fi veya titre art\u0131\u015f\u0131 al\u0131nm\u0131\u015ft\u0131r. Ayr\u0131ca iki \u00e7al\u0131\u015fmadaki (75,78) bruselloz tan\u0131l\u0131 hastalar aras\u0131nda yaln\u0131z k\u00fclt\u00fcr pozitifler ayr\u0131larak, sonu\u00e7lar\u0131 referans olarak yaln\u0131z k\u00fclt\u00fcr pozitiflerin al\u0131nd\u0131\u011f\u0131 meta-analizi sonucuna dahil edilmi\u015ftir. Meta-analizi sonucunda, ELISA IgG testi (n=1380) i\u00e7in duyarl\u0131l\u0131k %81 (%95 GA=%66-91), \u00f6zg\u00fcll\u00fck %97 (%95 GA=%89-99); ELISA IgM testi (n=1380) i\u00e7in duyarl\u0131l\u0131k %74 (%95 GA=%56 86), \u00f6zg\u00fcll\u00fck %99 (%95 GA=%87-99); ELISA IgM+IgG testi (n=715) i\u00e7in duyarl\u0131l\u0131k %87 (%95 GA=%50-97), \u00f6zg\u00fcll\u00fck %98 (%95 GA=%94-99) olarak bulunmu\u015ftur. Referans test olarak k\u00fclt\u00fcr pozitifli\u011finin al\u0131nd\u0131\u011f\u0131 \u00e7al\u0131\u015fmalar\u0131n ayr\u0131ca meta-analizi yap\u0131ld\u0131\u011f\u0131nda ise duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fck s\u0131ras\u0131yla, ELISA IgG testi (n=408) i\u00e7in %81 (%95 GA=%59-92) ve %91 (%95 GA=%72-97); ELISA IgM testi (n=307) i\u00e7in %83 (%95 GA=%56-95) ve %97 (%95 GA=%60-99) olarak hesaplanm\u0131\u015ft\u0131r. [STATA (StataCorp, ABD) program\u0131 ile havuz duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fck analizi yap\u0131labilmesi i\u00e7in en az d\u00f6rt \u00e7al\u0131\u015fma olmas\u0131 gerekmektedir. K\u00fclt\u00fcr pozitifli\u011fini referans alan ELISA IgM+IgG duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fcn\u00fcn ara\u015ft\u0131r\u0131ld\u0131\u011f\u0131 yaln\u0131z \u00fc\u00e7 \u00e7al\u0131\u015fma olmas\u0131 nedeni ile havuz analizi yap\u0131lamad\u0131.]<\/p>\n<p class=\"p3\">\u00c7ift\u00e7i ve arkada\u015flar\u0131n\u0131n (71) \u00e7al\u0131\u015fmas\u0131nda, ELISA testlerinin duyarl\u0131l\u0131\u011f\u0131 IgM i\u00e7in %71 (%95 GA=%54- 85), \u00f6zg\u00fcll\u00fc\u011f\u00fc %74 (%95 GA=%58-86); IgG i\u00e7in ise duyarl\u0131l\u0131k %97 (%95 GA=%85-100), \u00f6zg\u00fcll\u00fck %55 (%95 GA=%39-75) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Ertek ve arkada\u015flar\u0131n\u0131n (80) \u00e7al\u0131\u015fmas\u0131nda, ELISA kiti (Novum, Almanya) ile <i>Brucella<\/i>\u2019ya \u00f6zg\u00fc IgG ve IgM antikorlar\u0131 test edilmi\u015ftir. \u00c7al\u0131\u015fma sonucunda ELISA testlerinin duyarl\u0131l\u0131klar\u0131 ve \u00f6zg\u00fcll\u00fckleri s\u0131ras\u0131yla IgM i\u00e7in %100 (%95 GA=%89-100) ve %85 (%95 GA=%62-97); IgG i\u00e7in %81 (%95 GA=%64-93) ve %95 (%95 GA=%75-100) bulunurken IgM + IgG i\u00e7in %75 (%95 GA=%57-89) ve %94 (%95 GA=%73-100) olarak tespit edilmi\u015ftir.<\/p>\n<p class=\"p3\">Memish ve arkada\u015flar\u0131n\u0131n (81) \u00e7al\u0131\u015fmas\u0131nda, ELISA testleri (Genzyme Virotech GmbH, Almanya) ile IgG ve IgM antikorlar\u0131 test edilmi\u015f, test sonu\u00e7lar\u0131 pozitif veya negatif olarak kaydedilmi\u015ftir. S\u0131n\u0131rda olan sonu\u00e7lar yeniden test edilip pozitif veya negatif olarak do\u011frulanm\u0131\u015ft\u0131r. \u00c7al\u0131\u015fma sonucunda ELISA testlerinin duyarl\u0131l\u0131klar\u0131 ve \u00f6zg\u00fcll\u00fckleri s\u0131ras\u0131yla, IgM i\u00e7in %79 (%95 GA=%67-88) ve %100 (%95 GA=%95-100); IgG i\u00e7in %46 (%95 GA=%3-58) ve %97 (%95 GA=%90-100) bulunurken IgM+IgG i\u00e7in %94 (%95 GA=%85-98) ve %97 (%95 GA=%90-100) olarak tespit edilmi\u015ftir.<\/p>\n<p class=\"p3\">El-Hossain Aly Reda ve arkada\u015flar\u0131n\u0131n (77) \u00e7al\u0131\u015fmas\u0131nda, ELISA IgG testinde (Vircell SL, \u0130spanya) <i>B. abortus<\/i>\u2019un (S-99 su\u015fu) LPS antijeni ile kaplanm\u0131\u015f 96 oyuktan olu\u015fan bir mikrotitre plakas\u0131 kullan\u0131lm\u0131\u015ft\u0131r. ELISA IgG testinin duyarl\u0131l\u0131\u011f\u0131 %79 (%95 GA=%69-87), \u00f6zg\u00fcll\u00fc\u011f\u00fc %80 (%95 GA=%28-99) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Asaad ve Alqahtani\u2019nin (82) \u00e7al\u0131\u015fmas\u0131nda, Nisan 2010-Eyl\u00fcl 2011 tarihleri aras\u0131nda Suudi Arabistan\u2019\u0131n Najran ilinde King Khalid Hastanesi\u2019nde takipli 340 bruselloz \u015f\u00fcpheli hasta de\u011ferlendirilmi\u015ftir. Hastalar semptom s\u00fcresine g\u00f6re; akut (&lt;2 ay) (n=180), subakut (2-12 ay) (n=110), kronik (&gt;1 y\u0131l) (n=50) olarak \u00fc\u00e7 gruba ayr\u0131lm\u0131\u015f ve kontrol grubu olarak 110 sa\u011fl\u0131kl\u0131 kan don\u00f6r\u00fc se\u00e7ilmi\u015ftir. \u00c7al\u0131\u015fma tasar\u0131m\u0131nda referans test olarak k\u00fclt\u00fcr pozitifli\u011fi, STA pozitifli\u011fi veya ELISA pozitifli\u011fi al\u0131nm\u0131\u015f olmakla birlikte yapm\u0131\u015f oldu\u011fumuz meta-analizinde ELISA testlerinin performans\u0131n\u0131 belirlemek i\u00e7in k\u00fclt\u00fcr pozitifli\u011fi ile kesin bruselloz olan 50 hasta dahil edilmi\u015ftir. Kan k\u00fclt\u00fcrleri, bifazik kan k\u00fclt\u00fcr\u00fc ortam\u0131 (bioM\u00e9rieux, Fransa) kullan\u0131larak 30 g\u00fcn boyunca %5-10 karbondioksit atmosferinde 37\u00b0C\u2019de ink\u00fcbe edilmi\u015f, alt k\u00fclt\u00fcrleme haftal\u0131k olarak yap\u0131lm\u0131\u015f ve \u015f\u00fcpheli koloniler standart tekniklere g\u00f6re tan\u0131mlanm\u0131\u015ft\u0131r. ELISA testi (Genzyme Virotech, Almanya) i\u00e7in &gt;11 Virotech \u201cunite\u201d (VE) pozitif kabul edilmi\u015ftir. ELISA testlerinin duyarl\u0131l\u0131klar\u0131 ve \u00f6zg\u00fcll\u00fckleri s\u0131ras\u0131yla, IgM i\u00e7in %84 (%95 GA= %71-93) ve %99 (%95 GA=%97-100); IgG i\u00e7in ise %96 (%95 GA=%86-100) ve %99 (%95 GA=%97-100) olarak bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Arabac\u0131 ve Oldacay\u2019\u0131n (78) yukar\u0131da belirtilen \u00e7al\u0131\u015fmas\u0131nda, ELISA IgM ve IgG testlerinde (Vircell SL, \u0130spanya) e\u015fik de\u011ferler s\u0131ras\u0131yla, 20 U ve 30 U al\u0131nm\u0131\u015ft\u0131r. Ara\u015ft\u0131rmac\u0131lar ELISA testlerinin duyarl\u0131l\u0131klar\u0131 ve \u00f6zg\u00fcll\u00fcklerini s\u0131ras\u0131yla, IgM i\u00e7in %50 (%95 GA=%41-85) ve %100 (%95 GA=%97-100); IgG i\u00e7in %66 (%95 GA=%57-74) ve %99 (%95 GA=%95-100); IgM + IgG i\u00e7in ise %34 (%95 GA=%26-43) ve %100 (%95 GA=%97- 100) olarak bulmu\u015flard\u0131r. Ayn\u0131 \u00e7al\u0131\u015fmada referans test olarak yaln\u0131z k\u00fclt\u00fcr pozitif olgular al\u0131n\u0131p alt analiz yap\u0131ld\u0131\u011f\u0131nda ise ELISA testlerinin duyarl\u0131l\u0131klar\u0131 ve \u00f6zg\u00fcll\u00fckleri s\u0131ras\u0131yla IgM i\u00e7in %89 (%95 GA=%52-100) ve %100 (%95 GA=%97-100); IgG i\u00e7in %89 (%95 GA=%52-100) ve %99 (%95 GA=%95-100) olarak hesaplanm\u0131\u015ft\u0131r.<\/p>\n<p class=\"p3\">S\u0131rmatel ve arkada\u015flar\u0131n\u0131n (75) \u00e7al\u0131\u015fmas\u0131nda, ELISA testlerinin duyarl\u0131l\u0131klar\u0131 ve \u00f6zg\u00fcll\u00fckleri s\u0131ras\u0131yla, IgM i\u00e7in %49 (%95 GA=%42-57) ve %100 (%95 GA=%83-100); IgG i\u00e7in %62 (%95 GA=%55-68) ve %100 (%95 GA=%83-100) olarak hesaplanm\u0131\u015ft\u0131r. Ayn\u0131 \u00e7al\u0131\u015fmada referans test olarak yaln\u0131z k\u00fclt\u00fcr pozitif olgular al\u0131n\u0131p alt analiz yap\u0131ld\u0131\u011f\u0131nda ise ELISA testlerinin duyarl\u0131l\u0131klar\u0131 ve \u00f6zg\u00fcll\u00fckleri s\u0131ras\u0131yla, IgM i\u00e7in %62 (%95 GA=%38- 82) ve %100 (%95 GA=%83-100); IgG i\u00e7in %86 (%95 GA=%64-97) ve %100 (%95 GA=%83-100) olarak hesaplanm\u0131\u015ft\u0131r.<\/p>\n<p class=\"p3\">Vrioni ve arkada\u015flar\u0131 (76), ELISA testlerinin duyarl\u0131l\u0131klar\u0131 ve \u00f6zg\u00fcll\u00fcklerini s\u0131ras\u0131yla, IgM i\u00e7in %62 (%95 GA=%55-68) ve %100 (%95 GA=93-100); IgG i\u00e7in %91 (%95 GA=%86-94) ve %100 (%95 GA= %93-100); IgM + IgG i\u00e7in ise %99 (%95 GA=%96-100) ve %100 (%95 GA=%93-100) olarak bulmu\u015flard\u0131r. (Bkz. Ek \u015eekil 13-16 ve Ek Tablo 1, 6, 7)<\/p>\n<p class=\"p3\"><strong>\u00d6neri Gerek\u00e7esi: <\/strong>Duyarl\u0131l\u0131\u011f\u0131n RB ve STA testlerinden daha d\u00fc\u015f\u00fck olmas\u0131, testin \u00e7al\u0131\u015f\u0131lmas\u0131 i\u00e7in cihaz ve kit gereksinimi, daha maliyetli olmas\u0131 gerek\u00e7eleriyle ilk basamak tan\u0131da kullan\u0131m\u0131 \u00f6nerilmemi\u015ftir.<\/p>\n<p class=\"p3\"><strong>Bilgi a\u00e7\u0131\u011f\u0131:<\/strong> Analize dahil edilen \u00e7al\u0131\u015fmalarda kullan\u0131lan ELISA kitleri farkl\u0131d\u0131r. ELISA sonu\u00e7lar\u0131 i\u00e7in e\u015fik de\u011ferler baz\u0131 \u00e7al\u0131\u015fmalarda belirtilmemi\u015ftir. Belirtilen \u00e7al\u0131\u015fmalarda ise farkl\u0131 de\u011ferler e\u015fik de\u011fer olarak al\u0131nm\u0131\u015ft\u0131r. \u00c7al\u0131\u015fmalar\u0131n \u00e7o\u011funda brusellozun klinik tan\u0131mlar\u0131 (akut-kronik-relaps) yap\u0131lmam\u0131\u015ft\u0131r. ELISA testlerinin performanslar\u0131n\u0131 daha iyi de\u011ferlendirebilmek i\u00e7in; prospektif, yeterli \u00f6rneklem b\u00fcy\u00fckl\u00fc\u011f\u00fcne sahip, akut-kronik ve relaps tan\u0131mlar\u0131n\u0131n iyi tariflendi\u011fi, ayn\u0131 ELISA kitlerinin kullan\u0131ld\u0131\u011f\u0131, e\u015fik de\u011ferlerin net belirlendi\u011fi \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n<h4 class=\"p2\">4- Brusellozdan ku\u015fkulan\u0131lan hastalarda polimeraz zincir reaksiyonu (PCR) temelli testlerin tan\u0131daki yeri nedir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Bruselloz tan\u0131s\u0131nda PCR temelli testlerin duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fc y\u00fcksektir. Bununla birlikte pahal\u0131 olmalar\u0131, deneyimli personel ve teknik donan\u0131m gerektirmeleri nedeniyle ilk a\u015famada tan\u0131 testi olarak kullan\u0131m\u0131 \u00f6nerilmez. Wright STA test sonucu negatif \u00e7\u0131kmas\u0131na ra\u011fmen klinik ku\u015fkunun devam etti\u011fi hastalarda ve k\u00fclt\u00fcr sonucunun beklenmesinin tan\u0131 ve tedaviyi geciktirerek hastada olumsuz sonu\u00e7lara yol a\u00e7abilece\u011fi d\u00fc\u015f\u00fcn\u00fcld\u00fc\u011f\u00fc durumlarda bruselloz tan\u0131s\u0131 koymak i\u00e7in PCR temelli testlerin kullan\u0131m\u0131 \u00f6nerilir (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> \u00d6neri ile iligili kan\u0131tlar, bruselloz tan\u0131s\u0131nda PCR testinin duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fcn\u00fcn ara\u015ft\u0131r\u0131ld\u0131\u011f\u0131 11 kesitsel \u00e7al\u0131\u015fman\u0131n meta-analizine dayanmaktad\u0131r. Dahil edilen \u00e7al\u0131\u015fmalarda referans test olarak ikisinde (74,83) k\u00fclt\u00fcr pozitifli\u011fi, \u00fc\u00e7\u00fcnde (77,84,85) STA pozitifli\u011fi, d\u00f6rd\u00fcnde (65,68,72,73) k\u00fclt\u00fcr ve\/veya STA pozitifli\u011fi, ikisinde ise (63,75) k\u00fclt\u00fcr ve\/veya STA pozitifli\u011fi veya titre art\u0131\u015f\u0131 al\u0131nm\u0131\u015ft\u0131r. Meta-analizine t\u00fcm \u00e7al\u0131\u015fmalar (n=3067) dahil edildi\u011finde PCR testinin duyarl\u0131l\u0131\u011f\u0131 %93 (%95 GA=%75-98) ve \u00f6zg\u00fcll\u00fc\u011f\u00fc %98 (%95 GA= %92-99) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Alvarez Ojeda ve arkada\u015flar\u0131 (83), Meksika\u2019da 2015 y\u0131l\u0131nda y\u00fcr\u00fctt\u00fckleri \u00e7al\u0131\u015fmaya farkl\u0131 ekonomik ko\u015fullara sahip olan brusellozu d\u00fc\u015f\u00fcnd\u00fcren semptomu bulunan ki\u015filer ile semptomu olmayan ancak brusellozlu hastalarla birlikte ya\u015fayan 92 ki\u015fiyi dahil etmi\u015ftir. Ara\u015ft\u0131rmac\u0131lar bu \u00e7al\u0131\u015fmada, RB, STA, 2-merkaptoetanol (2-ME) ve k\u00fclt\u00fcr pozitif olgularda PCR testinin duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fcn\u00fc ayr\u0131 ayr\u0131 hesaplam\u0131\u015ft\u0131r. <i>Brucella<\/i> <i>abortus<\/i>\u2019un d\u0131\u015f zar\u0131n\u0131n imm\u00fcnojenik 31 KDa proteinini kodlayan genin (BCSP31: <i>Brucella<\/i> cinsine \u00f6zg\u00fcd\u00fcr ve <i>B. abortus<\/i>, <i>B. melitensis<\/i> ve <i>B. suis<\/i>\u2019te korunur) bir k\u0131sm\u0131n\u0131 \u00e7o\u011faltan primerler kullan\u0131lm\u0131\u015ft\u0131r [B4 (5\u2019-TGGCTC GGTTGCCAATATCAA-3\u2019) ve B5 (5\u2019-CGCGCTTG CCTTTCAGGTCTG-3\u2019) sekanslar\u0131]. Bu \u00e7al\u0131\u015fmada yer alan 31 hastaya ait STA verileri, STA e\u015fik de\u011feri bizim rehber \u00e7al\u0131\u015fmam\u0131zda kabul etti\u011fimiz \u22651\/160 yerine \u22651\/80 olarak al\u0131nd\u0131\u011f\u0131 i\u00e7in analize dahil edilmedi. PCR \u00fcr\u00fcnlerinin miktar\u0131n\u0131n ELISA ile \u00f6l\u00e7\u00fcld\u00fc\u011f\u00fc PCR-ELISA testi ile bruselloz kabul edilen 92 olgu aras\u0131nda k\u00fclt\u00fcr pozitif olan alt\u0131 ki\u015fi analize dahil edilerek hesapland\u0131\u011f\u0131nda PCR testinin duyarl\u0131l\u0131\u011f\u0131 %100 (%95 GA=%54-100) ve \u00f6zg\u00fcll\u00fc\u011f\u00fc %80 (%95 GA=%70-88) bulundu.<\/p>\n<p class=\"p3\">Purwar ve arkada\u015flar\u0131n\u0131n (74) \u00e7al\u0131\u015fmas\u0131nda, BMEI1162&#8217;nin a\u015fa\u011f\u0131 y\u00f6n\u00fcndeki IS711 gen b\u00f6lgesi (Gen bankas\u0131 eri\u015fim numaras\u0131: NC_003317) DNA amplifikasyonu i\u00e7in hedef olarak kullan\u0131lm\u0131\u015ft\u0131r; primerler, 279bp amplifikasyon \u00fcr\u00fcn\u00fc veren ileri primer (5\u2019AAC AAG CGG CAC CCC TAA AA3\u2019) ve revers primer (5\u2019CAT GCG CTA TGA TCT GGT TACG3\u2019)\u2019dir. Testin duyarl\u0131l\u0131\u011f\u0131 %100 (%95 GA=%83-100) iken \u00f6zg\u00fcll\u00fc\u011f\u00fc %97 (%95 GA=%95-98) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">El-Hossain Aly Reda ve arkada\u015flar\u0131n\u0131n (77) \u00e7al\u0131\u015fmas\u0131nda, t\u00fcm <i>Brucella<\/i> t\u00fcrlerinin DNA\u2019s\u0131n\u0131 belirleyebilmek \u00fczere PrimerDesignTMgenesigkit ve oasigTaqMan 2x qPCRMastermix kullan\u0131lm\u0131\u015f ve tek basamakl\u0131 Applied Biosystem cihaz\u0131nda kantitatif ger\u00e7ek zamanl\u0131 PCR yap\u0131lm\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>\u00c7al\u0131\u015fmada PCR testinin duyarl\u0131l\u0131\u011f\u0131 %65 (%95 GA=%55-75), \u00f6zg\u00fcll\u00fc\u011f\u00fc ise %40 (%95 GA=%5-85) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Khodabakhshi ve arkada\u015flar\u0131n\u0131n (84) 2019 y\u0131l\u0131nda \u0130ran\u2019da yapt\u0131klar\u0131 \u00e7al\u0131\u015fmaya, Golestan \u00dcniversitesi T\u0131p Fak\u00fcltesi\u2019nde takipli 65 ate\u015fli ve bruselloz \u015f\u00fcpheli hasta dahil edilmi\u015ftir. Standart t\u00fcp agl\u00fctinasyon testinin referans test olarak al\u0131nd\u0131\u011f\u0131 bu \u00e7al\u0131\u015fmada, 29 hastada bruselloz do\u011frulanm\u0131\u015f olup 36 hastada d\u0131\u015flanm\u0131\u015ft\u0131r. Kan \u00f6rneklerinden DNA ekstraksiyonu, ticari bir DNA kan ekstraksiyon kiti (Stratech, \u0130ngiltere) ile \u00fcreticinin talimatlar\u0131na g\u00f6re yap\u0131lm\u0131\u015ft\u0131r. Primerler olarak, BCSP31 geni, 223bp amplifikasyon \u00fcr\u00fcn\u00fc veren ileri primer (5\u2019 TGG CTC GGT TGC CAA TAT CAA3\u2019) ve revers primer (5\u2019CGC GCT TGC CTT TCA GGT CTG3\u2019) kullan\u0131lm\u0131\u015ft\u0131r. Prob olarak ise FAM -ACGGGCGCAATCT -MGB -NFQ kullan\u0131lm\u0131\u015ft\u0131r. Ara\u015ft\u0131rmac\u0131lar bu \u00e7al\u0131\u015fmada PCR testinin duyarl\u0131l\u0131\u011f\u0131n\u0131 %55 (%95 GA=%36-74), \u00f6zg\u00fcll\u00fc\u011f\u00fcn\u00fc ise %83 (%95 GA=%67-94) bulmu\u015ftur.<\/p>\n<p class=\"p3\">Kuila ve arkada\u015flar\u0131n\u0131n (85) \u00e7al\u0131\u015fmas\u0131nda, Hindistan\u2019\u0131n Bat\u0131 Bengal eyaletinde bulunan Peerless Hastanesi ve B.K. Roy Ara\u015ft\u0131rma Merkezi\u2019ne ba\u015fvuran 2088 ate\u015fli hasta de\u011ferlendirmeye al\u0131nm\u0131\u015ft\u0131r. Dahil edilme kriteri olarak hastalar\u0131n en az \u00fc\u00e7 haftad\u0131r olan ate\u015f y\u00fcksekli\u011fi ve odak bulunamam\u0131\u015f olmas\u0131 kabul edilmi\u015ftir. Bu hastalar\u0131n 385\u2019inde STA referans al\u0131nd\u0131\u011f\u0131nda bruselloz tan\u0131s\u0131 do\u011frulan\u0131rken 1703\u2019\u00fcnde d\u0131\u015flanm\u0131\u015ft\u0131r. Serum \u00f6rneklerinden genomik DNA ekstraksiyonu Qiagen kan mini kiti (Qiagen, Almanya) ile yap\u0131lm\u0131\u015ft\u0131r. Kullan\u0131lan primerler, BCSP-B4(F)-TGG CTC GGT TGC CAA TAT CAA ve BCSP-B5(R)-CGC GCT TGC CTT TCA GGT CTG\u2019dir. Ara\u015ft\u0131rmac\u0131lar bu \u00e7al\u0131\u015fmada PCR testinin duyarl\u0131l\u0131\u011f\u0131n\u0131 %22 (%95 GA=%18-26), \u00f6zg\u00fcll\u00fc\u011f\u00fcn\u00fc ise %100 (%95 GA=%99-100) bulmu\u015ftur.<\/p>\n<p class=\"p3\">Asaad ve Alqahtani\u2019nin (82) \u00e7al\u0131\u015fmas\u0131nda, PCR testi ile <i>Brucella<\/i> spp.\u2019ye \u00f6zg\u00fc 31-kDa zar proteininin \u00fcretimini kodlayan gen i\u00e7indeki 223-bp&#8217;lik bir hedef dizinin tespiti i\u00e7in, spesifik primerler [ileri primer: 5\u2019-TGGCTCGGTTGCCAATATCAA-3\u2019 ve revers primer: 5\u2019- CGCGCTTGCCTTTCAGGTCTG-3\u2019 (Qiagen, ABD)] ve <i>Brucella<\/i> DNA izolasyonu i\u00e7in E.Z.N.A. ticari kiti (Omega Biotech, ABD) kullan\u0131lm\u0131\u015ft\u0131r. Bu \u00e7al\u0131\u015fma ile PCR testinin duyarl\u0131l\u0131\u011f\u0131 %76 (%95 GA=%62-87), \u00f6zg\u00fcll\u00fc\u011f\u00fc ise %100 (%95 GA=%99-100) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">\u00c7eken ve arkada\u015flar\u0131n\u0131n (79) \u00e7al\u0131\u015fmas\u0131nda, PCR i\u00e7in DNA \u00f6rnekleri hasta l\u00f6kositlerinden elde edilmi\u015ftir. Taze kandan l\u00f6kosit izolasyonu i\u00e7in ficoll (PAA Laboratories GmbH, Avusturya) kullan\u0131lm\u0131\u015ft\u0131r. DNA, DZ DNA izolasyon kiti (Dr. Zeydanl\u0131, T\u00fcrkiye) kullan\u0131larak fenol kloroform y\u00f6ntemi ile izole edilmi\u015ftir. <i>Brucella<\/i> <i>abortus<\/i>\u2019un 31 kDa\u2019luk antijenini kodlayan genin 223 baz \u00e7iftlik b\u00f6lgesinin \u00e7o\u011falt\u0131lmas\u0131 i\u00e7in B4 (5\u2019-TGG CTC GGT TGC CAA TAT CAA-3\u2019) (ileri primer) ve B5 (5\u2019-CGC GCT TGC CTT TCA GGT CTG-3\u2019) (revers primer) primerleri (MWG, Almanya) kullan\u0131lm\u0131\u015ft\u0131r. \u00c7al\u0131\u015fmada PCR testinin duyarl\u0131l\u0131\u011f\u0131 %97 (%95 GA=%85-100), \u00f6zg\u00fcll\u00fc\u011f\u00fc ise %100 (%95 GA=%83-100) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Morata ve arkada\u015flar\u0131 (86), Ocak 1999-Aral\u0131k 2001 tarihleri aras\u0131nda \u0130spanya\u2019n\u0131n Malaga ilinde, 57 aktif bruselloz tan\u0131l\u0131 hastaya ait 59 kan \u00f6rne\u011fini incelemi\u015ftir. Ayn\u0131 \u00e7al\u0131\u015fmada, ba\u015fka sebebe ba\u011fl\u0131 30 ate\u015fli hasta, daha \u00f6nce bruselloz tedavisi alan ve aktif yak\u0131nmas\u0131 olmayan 41 hasta, mesleksel bruselloz maruziyeti olup y\u00fcksek brusella antikorlar\u0131 olan asemptomatik 14 hasta ve 28 sa\u011fl\u0131kl\u0131 kan donor\u00fc olmak \u00fczere toplamda 113 ki\u015fi kontrol grubu olarak de\u011ferlendirmeye al\u0131nm\u0131\u015ft\u0131r. \u00c7al\u0131\u015fma kapsam\u0131nda, PCR-ELISA y\u00f6nteminin tan\u0131daki yeri ara\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. <i>Brucella<\/i> cinsinin t\u00fcm biyovarlar\u0131nda bulunan, 31 kDa b\u00fcy\u00fckl\u00fc\u011f\u00fcnde <i>B. abortus<\/i>\u2019un imm\u00fcnojenik bir zar proteinini kodlayan genin korunmu\u015f b\u00f6lgesinden 223-bp\u2019lik bir fragman amplifiye edilmi\u015f olup bir \u00e7ift 21 n\u00fckleotid primeri, B4 (5\u2019-TGG CTC GGT TGC CAA TAT CAA 3\u2019) ve B5 (5\u2019-CGC GCT TGC CTT TCA GGT CTG 3\u2019) (Amersham Pharmacia Biotech, \u0130spanya), amplifikasyon i\u015fleminde kullan\u0131lm\u0131\u015ft\u0131r. PCR testinin duyarl\u0131l\u0131\u011f\u0131 %95 (%95 GA=%86-99), \u00f6zg\u00fcll\u00fc\u011f\u00fc ise %96 (%95 GA=%90-99) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">S\u00fcr\u00fcc\u00fco\u011flu ve arkada\u015flar\u0131n\u0131n (87) 2009\u2019da yay\u0131mlanan \u00e7al\u0131\u015fmas\u0131nda, 24 ayl\u0131k d\u00f6nemde Atat\u00fcrk E\u011fitim ve Ara\u015ft\u0131rma Hastanesi ile Celal Bayar \u00dcniversitesi T\u0131p Fak\u00fcltesi Hastanesi\u2019nde takipli 50 bruselloz hastas\u0131 ve 30 sa\u011fl\u0131kl\u0131 kan don\u00f6r\u00fc \u00e7al\u0131\u015fmaya dahil edilmi\u015ftir. Farkl\u0131 klinik formlardaki brusellozlu hastalarda h\u0131zl\u0131 tan\u0131da ge\u00e7ek zamanl\u0131 PCR y\u00f6ntemi konvansiyonel y\u00f6ntemler ile kar\u015f\u0131la\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. Ara\u015ft\u0131rmac\u0131lar bu \u00e7al\u0131\u015fmada, PCR testinin duyarl\u0131l\u0131\u011f\u0131n\u0131 %88 (%95 GA=%76-95), \u00f6zg\u00fcll\u00fc\u011f\u00fcn\u00fc ise %100 (%95 GA=%88-100) bulmu\u015ftur.<\/p>\n<p class=\"p3\">Mitka ve arkada\u015flar\u0131n\u0131n (88) 2007 y\u0131l\u0131nda yay\u0131mlanan \u00e7al\u0131\u015fmas\u0131nda, 1998-2004 y\u0131llar\u0131 aras\u0131nda Yunanistan\u2019\u0131n Selanik kentinde infeksiyon hastal\u0131klar\u0131 hastanesinde bruselloz tan\u0131s\u0131 ile takipli 200 hastaya ait 4926 kan \u00f6rne\u011fi (1642 periferal tam kan, 1642 \u201cbuffy coat\u201d \u00f6rne\u011fi ve 1642 serum \u00f6rne\u011fi) \u00e7al\u0131\u015fma grubuna al\u0131nm\u0131\u015ft\u0131r. Kontrol grubu olarak, 50 sa\u011fl\u0131kl\u0131 kontrol, 50 bakteriyel infeksiyonu (<i>Salmonella, Yersinia, E. coli, Enterobacter aerogenes, Klebsiella pneumoniae, H. influenzae ve Pseudomonas aeruginosa<\/i>) olan hasta belirlenmi\u015ftir. Bu \u00e7al\u0131\u015fmada akut ve relaps brusellozun h\u0131zl\u0131 tan\u0131s\u0131nda d\u00f6rt farkl\u0131 PCR metodu k\u00fclt\u00fcr ve serolojik testler ile kar\u015f\u0131la\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. Birinci PCR y\u00f6nteminde 223-bp\u2019lik bir fragman\u0131 amplifiye eden, B4 (5\u2019-TGG CTC GGT TGC CAA TAT CAA 3\u2019) ve B5 (5\u2019-CGC GCT TGC CTT TCA GGT CTG 3\u2019) primerleri kullan\u0131lm\u0131\u015ft\u0131r. \u0130kinci PCR y\u00f6nteminde amp2 gen b\u00f6lgesininin 193 bp\u2019lik par\u00e7as\u0131n\u0131 amplifiye eden JPF (5\u2019-GCG CTC AGG CTG CCG ACG CAA 3\u2019) ve JPR (5\u2019-ACC AGC CAT TGC GGT CGG TA 3\u2019) kullan\u0131lm\u0131\u015ft\u0131r. \u00dc\u00e7\u00fcnc\u00fc y\u00f6ntemde ise ayn\u0131 gen b\u00f6lgesinin 282 pb\u2019lik fragman\u0131n\u0131 kodlayan P1 (5\u2019-TGG AGG TCA GAA ATG AAC 3\u2019) ve P2 (5\u2019-GAG TGC GAA ACG AGC GC 3\u2019) primerleri kullan\u0131lm\u0131\u015ft\u0131r. D\u00f6rd\u00fcnc\u00fc PCR y\u00f6nteminde ise pb26 gen b\u00f6lgesinin 1029 bp\u2019lik alan\u0131n\u0131 amplifiye eden 26A (5\u2019-GCC CCT GAC ATA ACC CGC TT 3\u2019) ve 26B (5\u2019-GAG CGT GAC ATT TGC CGA TA 3\u2019) primerleri kullan\u0131lm\u0131\u015ft\u0131r. Bu \u00e7al\u0131\u015fmada t\u00fcm PCR testlerinde duyarl\u0131l\u0131k %95.5-100 iken \u00f6zg\u00fcll\u00fck %100 olarak bulunmu\u015ftur. Analize dahil edilen di\u011fer \u00e7al\u0131\u015fmalarda \u00e7o\u011funlukla B4 ve B5 primerleri kullan\u0131ld\u0131\u011f\u0131 i\u00e7in son analize birinci PCR y\u00f6nteminin serumda \u00e7al\u0131\u015f\u0131lm\u0131\u015f sonu\u00e7lar\u0131 dahil edildi\u011finde; duyarl\u0131l\u0131k %100 (%95 GA=%98-100), \u00f6zg\u00fcll\u00fck %100 (%95 GA=%98-100) bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Vrioni ve arkada\u015flar\u0131n\u0131n (76) 2004 y\u0131l\u0131nda yay\u0131mlanan \u00e7al\u0131\u015fmas\u0131nda, PCR \u00fcr\u00fcnlerinin miktar\u0131n\u0131n ELISA ile \u00f6l\u00e7\u00fcld\u00fc\u011f\u00fc PCR-ELISA testinin tan\u0131sal de\u011feri ara\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. Primerler olarak B4 (5\u2019- TGG CTC GGT TGC CAA TAT CAA 3\u2019) ve B5 (5\u2019-CGC GCT TGC CTT TCA GGT CTG 3\u2019) (MWG-Biotech, Almanya) kullan\u0131lm\u0131\u015ft\u0131r. Bu \u00e7al\u0131\u015fmada duyarl\u0131l\u0131k %99 (%95 GA=%97%-100), \u00f6zg\u00fcll\u00fck %100 (%95 GA= %93-100) bulunmu\u015ftur. (Bkz. Ek \u015eekil 17, 18 ve Ek Tablo 1, 8, 9)<\/p>\n<p class=\"p3\"><strong>\u00d6neri Gerek\u00e7esi:<\/strong> Testin \u00e7al\u0131\u015f\u0131lmas\u0131 i\u00e7in deneyimli personel ve ekipman gereksinimi, olduk\u00e7a maliyetli olmas\u0131, agl\u00fctinasyon testlerinin en az PCR kadar duyarl\u0131 olmas\u0131 gibi sebeplerle ilk basamak tan\u0131da kullan\u0131m\u0131 \u00f6nerilmemi\u015ftir.<\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> PCR testinde kullan\u0131lan primerlerin ve y\u00f6ntemlerin ayn\u0131 oldu\u011fu daha fazla say\u0131da \u00e7al\u0131\u015fmaya ihtiya\u00e7 vard\u0131r.<\/p>\n<h4 class=\"p2\">5- N\u00f6robruselloz tan\u0131s\u0131nda hangi tan\u0131sal testler tercih edilmelidir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> N\u00f6robrusellozdan ku\u015fkulan\u0131lan hastalarda kesin tan\u0131 i\u00e7in, BOS\u2019ta h\u00fccre say\u0131m\u0131, protein ve glukoz \u00f6l\u00e7\u00fcmleri, kan ve BOS k\u00fclt\u00fcr\u00fc, serum ve BOS\u2019ta Wright STA testi ve\/veya Coombs\u2019lu Wright STA testlerinin hepsinin bir arada yap\u0131lmas\u0131 \u00f6nerilir (<i>\u00c7ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Az say\u0131da do\u011frulanm\u0131\u015f n\u00f6robruselloz tan\u0131s\u0131 alan olgudan elde edilen verilerde, BOS\u2019ta ELISA ile <i>Brucella<\/i> spp. IgM ve\/veya IgG bak\u0131lmas\u0131n\u0131n, BOS Wright STA testine k\u0131yasla daha duyarl\u0131 oldu\u011fu g\u00f6r\u00fcld\u00fc\u011f\u00fcnden, ula\u015f\u0131labilen yerlerde BOS\u2019ta Wright STA yerine BOS\u2019ta ELISA IgM\/IgG testinin tercih edilmesi d\u00fc\u015f\u00fcn\u00fclebilir (<i>\u00c7ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, zay\u0131f \u00f6neri<\/i>).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> N\u00f6robruselloz tan\u0131s\u0131 alan ve tan\u0131 i\u00e7in kullan\u0131lm\u0131\u015f testlerin belirtildi\u011fi toplam <span class=\"Apple-converted-space\">\u00a0 <\/span>1022 olgu i\u00e7eren yay\u0131nla (33-54, 89-210) yapt\u0131\u011f\u0131m\u0131z sistematik derleme ve IPD meta-analizinde, n\u00f6robruselloz tan\u0131s\u0131nda, alt\u0131n standart tan\u0131 testi olan BOS k\u00fclt\u00fcr\u00fc pozitifli\u011finin \u00e7ok d\u00fc\u015f\u00fck oranda belirlendi\u011fi ve bu testin n\u00f6robruselloz tan\u0131s\u0131ndaki duyarl\u0131l\u0131\u011f\u0131n\u0131n %18.4 oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. N\u00f6robruselloz tan\u0131s\u0131nda en s\u0131k kullan\u0131lan testlerin, <i>Brucella<\/i> antikorlar\u0131n\u0131 saptayan BOS\u2019ta STA ve Coombs\u2019lu STA testi oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. BOS\u2019ta RB testi, \u00e7al\u0131\u015f\u0131lan olgular\u0131n %57.3\u2019\u00fcnde, BOS\u2019ta STA testi ise \u00e7al\u0131\u015f\u0131lan olgular\u0131n %69.06\u2019unda pozitif saptanm\u0131\u015ft\u0131r. Ancak incelenen \u00e7al\u0131\u015fmalarda BOS agl\u00fctinasyon testinde pozitif titre d\u00fczeyi i\u00e7in farkl\u0131 e\u015fik de\u011ferler kullan\u0131lm\u0131\u015ft\u0131r ve bir fikir birli\u011fi bulunmamaktad\u0131r. \u00c7al\u0131\u015fmalar\u0131n \u00e7o\u011funda herhangi bir titrede bulunan pozitif sonu\u00e7, tan\u0131 i\u00e7in yeterli kabul edilmi\u015ftir. Ancak alt s\u0131n\u0131r olarak 1\/4-1\/80 gibi farkl\u0131 e\u015fik de\u011ferler al\u0131n\u0131p, herhangi bir titrede saptanan pozitifli\u011fin anlaml\u0131 kabul edildi\u011fi belirtilmi\u015ftir (33-43, 89-94). Guven ve arkada\u015flar\u0131n\u0131n (33) \u00e7al\u0131\u015fmas\u0131nda, BOS\u2019ta agl\u00fctinasyon testinin pozitif e\u015fik de\u011feri 1:8 olarak al\u0131nd\u0131\u011f\u0131nda; duyarl\u0131l\u0131k %94 (%95 GA= %83-99), \u00f6zg\u00fcll\u00fck %96 (%95 GA= %89-99), pozitif prediktif de\u011feri %94 (%95 GA= %83-99) ve negatif prediktif de\u011feri %96 (%95 GA=%89-99) oldu\u011fu belirtilmi\u015ftir. BOS\u2019ta yap\u0131lan antikor testlerinin pozitif sonucu, serumdaki IgG\u2019nin spontan dif\u00fczyonuna ba\u011fl\u0131 olabilece\u011finden, kesin olarak intratekal IgG sentezi oldu\u011funu g\u00f6stermemektedir (92).<span class=\"Apple-converted-space\">\u00a0 <\/span>N\u00f6roborelyoz tan\u0131s\u0131nda, BOS\/serum antikor indeksinin belirlenmesi i\u00e7in, valide edilmi\u015f metodoloji kullan\u0131larak ve e\u015fzamanl\u0131 olarak BOS ve serum numunelerinin al\u0131nmas\u0131 \u00f6nerilmektedir (211). Brusellozda n\u00f6rolojik tutulumun do\u011frulanmas\u0131 i\u00e7in n\u00f6roborelyozda oldu\u011fu gibi BOS\u2019ta herhangi bir titrede agl\u00fctinasyon testi pozitifli\u011fi yerine BOS\/serum antikor indeksi kullan\u0131lmas\u0131n\u0131n gerekip gerekmedi\u011fini ara\u015ft\u0131ran \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Beyin ve omurilik s\u0131v\u0131s\u0131 k\u00fclt\u00fcr ve STA testi sonu\u00e7lar\u0131 tek tek sunulan olgu raporlar\u0131 ve \u00e7al\u0131\u015fmalar de\u011ferlendirilerek, BOS k\u00fclt\u00fcr\u00fc pozitif olan hastalarda Wright STA ve ELISA testlerinin duyarl\u0131l\u0131\u011f\u0131n\u0131 tan\u0131mlamak \u00fczere alt grup analizi yap\u0131ld\u0131. BOS k\u00fclt\u00fcr\u00fcnde \u00fcremesi olan ve BOS\u2019ta STA \u00e7al\u0131\u015f\u0131lan 84 olgunun 64 (%76.2)\u2019\u00fcnde STA pozitifli\u011fi saptand\u0131. Ancak yukar\u0131da da belirtildi\u011fi gibi bu olgu raporu ve \u00e7al\u0131\u015fmalarda kabul edilen pozitif e\u015fik de\u011fer farkl\u0131l\u0131k g\u00f6stermektedir. S\u0131n\u0131r de\u011fer olarak 1\/4 titre \u00fczerindeki pozitifliklerin kabul edildi\u011fi \u00e7al\u0131\u015fmalar (33,36,38,40,41,89,94,95,99,100,108,117,124,127,138,151,157,160,162,165,171,176,182,185,187,190,199,204,206) de\u011ferlendirildi\u011findeyse 52 BOS k\u00fclt\u00fcr\u00fc pozitif hastan\u0131n 41 (%78.8)\u2019inde STA\u2019\u0131n pozitif oldu\u011fu g\u00f6r\u00fcld\u00fc. BOS k\u00fclt\u00fcr\u00fcnde \u00fcremesi olan ve BOS\u2019ta ELISA ile <i>Brucella<\/i> spp. antikorlar\u0131 bak\u0131lm\u0131\u015f toplam 20 hastan\u0131n 19 (%95)\u2019unda IgM ve\/veya IgG pozitifli\u011fi saptanm\u0131\u015ft\u0131r. N\u00f6robruselloz olmayan hastalar\u0131n BOS\u2019unun incelenmesi m\u00fcmk\u00fcn olmad\u0131\u011f\u0131 i\u00e7in kullan\u0131lan testlerin \u00f6zg\u00fcll\u00fckleri belirlenememi\u015ftir.<\/p>\n<p class=\"p3\">Beyin ve omurilik s\u0131v\u0131s\u0131\u2019nda ELISA ile IgM ve\/veya IgG testi, bak\u0131lan olgular\u0131n %91.6\u2019s\u0131nda pozitif saptanm\u0131\u015ft\u0131r. Serum ve BOS\u2019ta IFA ve kompleman fiksasyon testi \u00e7al\u0131\u015f\u0131lan az say\u0131da olgu bulunmaktad\u0131r. Ayn\u0131 \u015fekilde serum ve BOS\u2019ta PCR ile <i>Brucella<\/i> DNA veya 16S rRNA\u2019y\u0131 de\u011ferlendiren yeterli say\u0131da hasta bildirimi bulunmamaktad\u0131r. Yeni nesil dizileme [Next-generation sequencing (NGS)] ile BOS\u2019ta <i>Brucella <\/i>DNA bak\u0131lan alt\u0131 olgunun tamam\u0131nda pozitiflik saptanm\u0131\u015ft\u0131r (96-98). Bu test umut vaat etmekle birlikte di\u011fer testlerle kar\u015f\u0131la\u015ft\u0131r\u0131larak yap\u0131lan ve daha fazla say\u0131da olgu i\u00e7eren \u00e7al\u0131\u015fmalara ihtiya\u00e7 bulunmaktad\u0131r.<\/p>\n<p class=\"p3\">N\u00f6robrusellozlu olgular\u0131n BOS\u2019unda lenfositoz, protein\u00a0y\u00fcksekli\u011fi, glukoz d\u00fc\u015f\u00fckl\u00fc\u011f\u00fc g\u00f6r\u00fclebilmektedir. Ger\u00e7ekle\u015ftirmi\u015f oldu\u011fumuz sistematik derleme ve analizde n\u00f6robruselloz olgular\u0131n\u0131n BOS\u2019unda ortalama 156 l\u00f6kosit g\u00f6r\u00fclm\u00fc\u015f, BOS l\u00f6kosit say\u0131s\u0131 olgular\u0131n %87\u2019sinde ml\u2019de &gt;5 h\u00fccre olarak bulunmu\u015ftur. Ayn\u0131 analizde BOS ortalama protein d\u00fczeyi 211.7 mg\/dl olup BOS proteini olgular\u0131n %85.3\u2019\u00fcnde \u226545 mg\/dl, BOS glukozu olgular\u0131n %56.8\u2019inde &lt;45 mg\/dl, BOS\/kan glukozu ortalamas\u0131 0.36 ve BOS\/kan glukozu olgular\u0131n %53\u2019\u00fcnde &lt;0.4 bulunmu\u015ftur.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">N\u00f6robruselloz tan\u0131s\u0131 alan olgular\u0131n 444\u2019\u00fcne kraniyal BT veya MRI \u00e7ekilmi\u015ftir. Bu g\u00f6r\u00fcnt\u00fclemelerde 220 olgu (%49.5)\u2019da anormal bulgu saptanm\u0131\u015ft\u0131r. (Bkz. Ek Tablo 10).<\/p>\n<p class=\"p3\"><strong>\u00d6nerilerin Gerek\u00e7esi:<\/strong> N\u00f6robruselloz tan\u0131s\u0131nda kullan\u0131lan klasik testlerin hi\u00e7birinin duyarl\u0131l\u0131\u011f\u0131 %100 olmad\u0131\u011f\u0131 gibi, bu testlerin n\u00f6robruselloz tan\u0131s\u0131ndaki \u00f6zg\u00fcll\u00fc\u011f\u00fcn\u00fc ara\u015ft\u0131ran \u00e7al\u0131\u015fma da bulunamam\u0131\u015ft\u0131r. Var olan s\u0131n\u0131rl\u0131 verilerle yapt\u0131\u011f\u0131m\u0131z sistemetik derleme ve IPD meta-analizinin sonucunda; n\u00f6robrusellozdan \u015f\u00fcphelenilen olgular\u0131n tan\u0131s\u0131nda, hastal\u0131\u011f\u0131n a\u011f\u0131rl\u0131\u011f\u0131 ve neden olabilece\u011fi morbidite ve mortaliteler de dikkate al\u0131nd\u0131\u011f\u0131nda, yeterli duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011fe sahip di\u011fer bir test belirleninceye kadar, BOS\u2019ta h\u00fccre say\u0131m\u0131 ve biyokimyasal inceleme, kan ve BOS k\u00fclt\u00fcr\u00fc, Wright STA testi ve\/veya Coombs\u2019lu brusella agl\u00fctinasyon testleri veya BOS\u2019ta ELISA ile <i>Brucella<\/i> spp. IgG ve IgM testlerinin t\u00fcm\u00fcn\u00fcn bir arada yap\u0131lmas\u0131n\u0131n gerekli oldu\u011fu d\u00fc\u015f\u00fcn\u00fclm\u00fc\u015ft\u00fcr.<span class=\"Apple-converted-space\">\u00a0 <\/span>Ayr\u0131ca BOS\u2019ta <i>Brucella<\/i> spp. \u00fcremesiyle n\u00f6robruselloz tan\u0131s\u0131 alm\u0131\u015f s\u0131n\u0131rl\u0131 say\u0131daki kan\u0131tl\u0131 n\u00f6robruselloz olgusunda, Wright STA yerine ELISA ile BOS\u2019ta <i>Brucella<\/i> spp. IgM ve\/veya IgG bak\u0131lmas\u0131 halinde daha y\u00fcksek oranda pozitiflik belirlendi\u011fi (%95\u2019e kar\u015f\u0131l\u0131k %78.8) i\u00e7in, ula\u015f\u0131labilen yerlerde BOS\u2019ta STA yerine ELISA ile <i>Brucella<\/i> spp. IgG ve\/veya IgM temelli testlerin tercih edilebilece\u011fi d\u00fc\u015f\u00fcn\u00fclm\u00fc\u015ft\u00fcr.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131: <\/strong>Brusellozda n\u00f6rolojik tutulumun do\u011frulanmas\u0131 i\u00e7in n\u00f6roborelyoz tan\u0131s\u0131nda oldu\u011fu gibi BOS\u2019ta herhangi bir titrede agl\u00fctinasyon testi pozitifli\u011fi yerine BOS\/serum antikor indeksi kullan\u0131lmas\u0131n\u0131n gerekip gerekmedi\u011fini ara\u015ft\u0131ran \u00e7al\u0131\u015fmalara ihtiya\u00e7 bulunmaktad\u0131r.<\/p>\n<p class=\"p3\">Alt\u0131n standart tan\u0131 testi olan BOS k\u00fclt\u00fcr\u00fc ile BOS Wright\/Coombs\u2019lu <i>Brucella<\/i> agl\u00fctinasyon testi, ELISA, IFA ve PCR testlerini kar\u015f\u0131la\u015ft\u0131ran, duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fck bildirebilecek \u015fekilde tasarlanm\u0131\u015f \u00e7al\u0131\u015fmalara ihtiya\u00e7 bulunmaktad\u0131r.<\/p>\n<h4 class=\"p2\">6- Bruselloz tedavisinde alt\u0131 haftal\u0131k tedavi s\u00fcresi d\u00f6rt haftal\u0131k tedavi s\u00fcresinden \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Komplike bruselloz olgular\u0131n\u0131n (endokardit, n\u00f6robruselloz ve spondilit) d\u0131\u015flanarak bruselloz tedavi s\u00fcresinin kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131 \u00e7al\u0131\u015fmalar\u0131n meta-analizinde, d\u00f6rt haftal\u0131k rejimlerle kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, alt\u0131 haftal\u0131k antimikrobiyal tedavilerle relaps geli\u015fme riski daha d\u00fc\u015f\u00fck bulunmu\u015ftur. Akut bruselloz tan\u0131s\u0131 konulan hastalarda alt\u0131 haftal\u0131k tedavi kullan\u0131lmas\u0131 \u00f6nerilir (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<\/p>\n<h4 class=\"p17\">Kan\u0131tlar\u0131n \u00d6zeti:<\/h4>\n<p class=\"p14\"><strong><em>Etkinlik<\/em><\/strong><\/p>\n<p class=\"p3\">\u00d6neri ile ilgili kan\u0131tlar, akut brusellozda d\u00f6rt hafta ile alt\u0131 hafta s\u00fcren tedavileri kar\u015f\u0131la\u015ft\u0131ran randomize kontroll\u00fc \u00e7al\u0131\u015fmalar\u0131n meta-analizine dayanmaktad\u0131r. Konu ile ilgili yay\u0131nlanm\u0131\u015f alt\u0131 randomize kontroll\u00fc \u00e7al\u0131\u015fmaya ula\u015f\u0131lm\u0131\u015ft\u0131r (212-217). \u00c7al\u0131\u015fmalar\u0131n tamam\u0131nda, toplam 613 hastada tedavi rejimlerinin relaps geli\u015fimine etkisi, d\u00f6rt \u00e7al\u0131\u015fmada (213,214,216,217) toplam 438 hastada tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131na etkisi de\u011ferlendirilmi\u015ftir. \u00c7al\u0131\u015fmalar aras\u0131nda relaps geli\u015fimi i\u00e7in takip s\u00fcreleri de\u011fi\u015fken olup, \u00fc\u00e7 \u00e7al\u0131\u015fmada 12 ay (212,214,216), iki \u00e7al\u0131\u015fmada alt\u0131 ay (213,217), bir \u00e7al\u0131\u015fmada ise \u00fc\u00e7 ayd\u0131r (215). \u00c7al\u0131\u015fmalar\u0131n \u00fc\u00e7\u00fcnde komplike ve uzun tedavi gerektiren hastalar (n\u00f6robruselloz, endokardit ve spondilit) d\u0131\u015flan\u0131rken (212,216,217), di\u011fer \u00fc\u00e7 \u00e7al\u0131\u015fmada bu hastalar dahil edilmi\u015ftir (213-215). Komplike ve uzun tedavi gerektiren olgular\u0131n d\u0131\u015fland\u0131\u011f\u0131 \u00e7al\u0131\u015fmalar de\u011ferlendirildi\u011finde d\u00f6rt haftal\u0131k tedaviler ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda (n=433) \u2265 6 haftal\u0131k tedavilerde relaps geli\u015fme riski d\u00fc\u015f\u00fck saptanm\u0131\u015ft\u0131r [\u201crisk ratio\u201d (RR)=0.52, %95 GA=0.32-0.85;<span class=\"s1\"><i> I<\/i><sup>2<\/sup><\/span>=38]. Tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, komplike ve uzun tedavi gerektiren olgular\u0131n d\u0131\u015fland\u0131\u011f\u0131 2 \u00e7al\u0131\u015fmada toplam 287 hastada de\u011ferlendirilmi\u015f ve her iki grup aras\u0131nda anlaml\u0131 fark saptanmam\u0131\u015ft\u0131r (RR=0.50, %95 GA=0.18-1.42;<span class=\"s1\"><i> I<\/i><sup>2<\/sup><\/span>=0.0).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Hastalar\u0131n b\u00fcy\u00fck bir \u00e7o\u011funlu\u011fu iki farkl\u0131 \u00e7al\u0131\u015fmadan al\u0131nm\u0131\u015ft\u0131r (212, 216). Solera ve arkada\u015flar\u0131 (212) taraf\u0131ndan yap\u0131lan \u00e7al\u0131\u015fma, randomize, \u00e7ift k\u00f6r ve \u00e7ok merkezli olarak tasarlanm\u0131\u015f, tedavi gerektiren komplike hastalar d\u0131\u015flanm\u0131\u015f (spondilit) ve relaps i\u00e7in takip s\u00fcresi 12 ay olarak belirlenmi\u015ftir. \u00c7al\u0131\u015fmada toplam 167 hasta randomize edilmi\u015ftir<sup>.<\/sup>; DOX-GEN kolunda yedi hasta, DOX-STREP kolunda ise be\u015f hasta spondilit nedeniyle \u00e7al\u0131\u015fmadan d\u0131\u015flanm\u0131\u015ft\u0131r. DOX-GEN kolunda d\u00f6rt hastada, DOX-STREP kolunda ise be\u015f hastada takip s\u00fcrecine uyumsuzluk ve klinisyen iste\u011fi nedeniyle sonu\u00e7 verilerine ula\u015f\u0131lamam\u0131\u015ft\u0131r. \u00c7al\u0131\u015fmada, DOX (30 g\u00fcn)-GEN (7 g\u00fcn) (n=73) ile DOX (45 g\u00fcn)-GEN (7 g\u00fcn) (n=73) tedavi rejimleri toplam 146 hastada relaps a\u00e7\u0131s\u0131ndan kar\u015f\u0131la\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>Relaps a\u00e7\u0131s\u0131ndan her iki kol aras\u0131nda istatistiksel farkl\u0131l\u0131k saptanmam\u0131\u015ft\u0131r (RR=0.60, %95 GA=0.28-1.28).<span class=\"Apple-converted-space\">\u00a0 <\/span>Montejo ve arkada\u015flar\u0131 (216), randomize, a\u00e7\u0131k etiketli ve tek merkezli olarak yap\u0131lan \u00e7al\u0131\u015fmalar\u0131nda, alt\u0131 farkl\u0131 tedavi rejimini relaps ve tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan kar\u015f\u0131la\u015ft\u0131rm\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>\u00c7al\u0131\u015fmada, relaps i\u00e7in takip s\u00fcresi 12 ay olarak belirlenmi\u015ftir. Randomizasyon sonras\u0131 toplam 32 hasta [komplike olgular (n=21), tedavi ila\u00e7lar\u0131na alerji (n=5), daha \u00f6nce tedavi \u00f6yk\u00fcs\u00fc (n=6)] \u00e7al\u0131\u015fmadan d\u0131\u015flanm\u0131\u015ft\u0131r. On \u00fc\u00e7 hastada bir y\u0131l de\u011ferlendirmesi yap\u0131lamam\u0131\u015ft\u0131r. Meta-analizine, kombinasyon rejimleri alan hastalar dahil edilmi\u015f, tek tedavi rejimi uygulanan hastalar [rejim 2 (n=64), rejim 3 (n=71)] de\u011ferlendirmeye al\u0131nmam\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>D\u00f6rt hafta tedavi rejimleri [DOX-RIF (rejim 1, 28 g\u00fcn), n=65] ile \u22656 hafta tedavi rejimleri [DOX-STREP (rejim 4-6, 6 hafta), DOX-RIF (rejim 5-6, 6 hafta) (n=130)] kar\u015f\u0131la\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>D\u00f6rt hafta tedavi rejimleri ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda \u22656 hafta tedavi rejimleri d\u00fc\u015f\u00fck relaps geli\u015fimi ile ili\u015fkili iken (RR=0.32, %95 GA=0.15-0.70), tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 (RR=0.50, %95 GA=0.03-7.87) a\u00e7\u0131s\u0131ndan her iki grup aras\u0131nda anlaml\u0131 farkl\u0131l\u0131k saptanmam\u0131\u015ft\u0131r (216). (Bkz. Ek \u015eekil 19-21 ve Ek Tablo 11, 12)<\/p>\n<p class=\"p14\"><strong><em>G\u00fcvenlik<\/em><\/strong><\/p>\n<p class=\"p3\">\u00dc\u00e7 \u00e7al\u0131\u015fmada yer alan toplam 286 hastada, d\u00f6rt hafta ve \u22656 hafta tedavi rejimleri g\u00fcvenlik a\u00e7\u0131s\u0131ndan de\u011ferlendirilmi\u015ftir (212,214,215). Her iki grup aras\u0131nda yan etki geli\u015fimi a\u00e7\u0131s\u0131ndan farkl\u0131l\u0131k saptanmam\u0131\u015ft\u0131r (RR=1.00, %95 GA=0.69-1.44). Hastalar\u0131n b\u00fcy\u00fck bir \u00e7o\u011funlu\u011fu Solera ve arkada\u015flar\u0131 (212) taraf\u0131ndan y\u00fcr\u00fct\u00fclen \u00e7al\u0131\u015fmadan al\u0131nm\u0131\u015ft\u0131r. \u00c7al\u0131\u015fmada d\u00f6rt hafta tedavi kolunda %40 (n=29), \u2265 6 hafta tedavi kolunda ise %38 (n=28) yan etki geli\u015fimi saptanm\u0131\u015ft\u0131r. Yan etkilerin tamam\u0131 ciddi olmay\u0131p en s\u0131k saptananlar s\u0131ras\u0131yla fototoksite (n=31) ve gastrointestinal yan etkilerdir (epigastrik a\u011fr\u0131, bulant\u0131, kusma) (n=21). Her iki grup aras\u0131nda yan etki geli\u015fimi a\u00e7\u0131s\u0131ndan fark saptanmam\u0131\u015ft\u0131r (RR=0.97, %95 GA=0.64-1.45) (212). (Bkz. Ek \u015eekil 19-21 ve Ek Tablo 11, 12)<\/p>\n<p class=\"p3\"><strong>\u00d6neri Gerek\u00e7esi:<\/strong> Komplike olmayan bruselloz olgular\u0131nda d\u00f6rt hafta tedavi rejimleri ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda alt\u0131 hafta antibiyotik tedavisinin relaps geli\u015fimini azaltmadaki etkinli\u011fi, daha uzun antibiyotik tedavisinin potansiyel zararlar\u0131ndan (yan etki) fazlad\u0131r.<\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> \u00c7al\u0131\u015fmalarda farkl\u0131 tedavi kombinasyonlar\u0131, homojen olmayan hasta gruplar\u0131nda, de\u011fi\u015fken sonlan\u0131mlar a\u00e7\u0131s\u0131ndan kar\u015f\u0131la\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. \u00c7al\u0131\u015fmalar\u0131n pek \u00e7o\u011funda optimal \u00f6rneklem b\u00fcy\u00fckl\u00fckleri belirsizdir. Standart kombinasyon tedavi rejimlerini, homojen hasta gruplar\u0131nda (komplike olmayan hastalar), standart sonlan\u0131mlar i\u00e7in (relaps, takip s\u00fcreleri ve yan etki) kar\u015f\u0131la\u015ft\u0131ran prospektif randomize \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n<h4 class=\"p2\">7- Bruselloz tedavisinde doksisiklin + streptomisin kombinasyonu, doksisiklin + rifampisin kombinasyonundan \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Akut bruselloz tan\u0131s\u0131 alan hastalarda tedavi rejimlerinin kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131 \u00e7al\u0131\u015fmalar\u0131n meta-analizinde DOX-STREP rejimi, DOX-RIF rejimine g\u00f6re daha d\u00fc\u015f\u00fck tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 ve relapsla ili\u015fkili bulunmu\u015ftur. Her iki tedavi rejimi aras\u0131nda yan etki geli\u015fimi a\u00e7\u0131s\u0131ndan fark saptanmam\u0131\u015ft\u0131r. Kullan\u0131m zorlu\u011fu ve uyum sorunu ya\u015famayacak akut bruselloz tan\u0131l\u0131 hastalarda \u00f6ncelikle DOX-STREP kombinasyonunun kullan\u0131lmas\u0131 \u00f6nerilir <i>(D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, zay\u0131f \u00f6neri)<\/i>.<\/p>\n<h4 class=\"p17\">Kan\u0131tlar\u0131n \u00d6zeti:<\/h4>\n<p class=\"p14\"><em><strong>Etkinlik<\/strong><\/em><\/p>\n<p class=\"p3\">\u00d6neri ile ilgili kan\u0131tlar, akut brusellozda DOX-RIF ve DOX-STREP tedavi <span class=\"s2\">rejimlerini kar\u015f\u0131la\u015ft\u0131ran randomize kontroll\u00fc \u00e7al\u0131\u015fmalar\u0131n meta-analizine dayanmaktad\u0131r (213, 217-224). Meta-analizine, dokuz randomize kontroll\u00fc \u00e7al\u0131\u015fma dahil edilmi\u015f ve toplam 975 hastada tedavi rejimleri, relaps ve tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan kar\u015f\u0131la\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. DOX-RIF ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda DOX-STREP tedavi rejimi daha az tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 (RR=0.50, %95 GA=0.26-0.95) ve relaps (RR=0.36, %95 GA=0.23-0.56) geli\u015fimi ile ili\u015fkili bulunmu\u015ftur. \u00c7al\u0131\u015fmalar\u0131n d\u00f6rd\u00fcnde tedavi etkinli\u011fini etkileyebilecek komplike olgular\u0131n (n\u00f6robruselloz, endokardit, spondilit) d\u0131\u015fland\u0131\u011f\u0131 (216,218,221,222), be\u015f \u00e7al\u0131\u015fmada ise komplike olgular\u0131n dahil edildi\u011fi saptanm\u0131\u015ft\u0131r (213,219,220,223,224). DOX-RIF ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda DOX-STREP tedavi rejimi komplike olgular\u0131n dahil edildi\u011fi \u00e7al\u0131\u015fmalarda daha az tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 ile ili\u015fkili iken (RR=0.41, %95 GA=0.19-0.90), komplike olgular\u0131n d\u0131\u015fland\u0131\u011f\u0131 \u00e7al\u0131\u015fmalarda her iki rejim aras\u0131nda tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan fark saptanmam\u0131\u015ft\u0131r (RR=2.56, %95 GA=0.60-10.95). Relaps geli\u015fimi a\u00e7\u0131s\u0131ndan kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda komplike brusellozlu hastalar\u0131n dahil edildi\u011fi (RR=0.37, %95 GA=0.20-0.69) ve edilmedi\u011fi (RR=0.34, %95 GA=0.18-0.66) \u00e7al\u0131\u015fmalarda DOX-STREP tedavi rejimi daha az relaps geli\u015fimi ile ili\u015fkili bulunmu\u015ftur. Relaps geli\u015fimi i\u00e7in takip s\u00fcresinin alt\u0131 ay oldu\u011fu d\u00f6rt \u00e7al\u0131\u015fman\u0131n (RR=0.40, %95 GA=0.20-0.82) (213,218,220,221) ve 12 ay oldu\u011fu be\u015f \u00e7al\u0131\u015fman\u0131n (RR=0.33, %95 GA=0.18-0.59) meta-analizi sonucuna g\u00f6re (216,217,219,223,224) DOX-STREP rejimi DOX-RIF tedavi rejimine g\u00f6re daha az relaps geli\u015fimi ile ili\u015fkilidir.<\/span><\/p>\n<p class=\"p3\">Meta-analizine dahil edilen hastalar\u0131n b\u00fcy\u00fck \u00e7o\u011funlu\u011fu \u00fc\u00e7 \u00e7al\u0131\u015fmadan al\u0131nm\u0131\u015ft\u0131r (216,222,224). Montejo ve arkada\u015flar\u0131 (216), randomize, a\u00e7\u0131k etiketli ve tek merkezli \u00e7al\u0131\u015fmada, alt\u0131 farkl\u0131 tedavi rejimini kar\u015f\u0131la\u015ft\u0131rm\u0131\u015ft\u0131r. Randomizasyon sonras\u0131 toplam 32 hasta [komplike olgular (n=21), tedavi ila\u00e7lar\u0131na alerji (n=5), daha \u00f6nce tedavi \u00f6yk\u00fcs\u00fc (n=6) olanlar] \u00e7al\u0131\u015fmadan d\u0131\u015flanm\u0131\u015ft\u0131r. On \u00fc\u00e7 hastan\u0131n da bir y\u0131l de\u011ferlendirmesi yap\u0131lamam\u0131\u015ft\u0131r. Meta-analizine kombinasyon rejimleri alan hastalar dahil edilmi\u015f, DOX-RIF (rejim 1 ve 5, n=111 ve DOX-STREP (rejim 4 ve 6, n=84) tedavi rejimleri kar\u015f\u0131la\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. DOX-RIF ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda DOX-STREP daha d\u00fc\u015f\u00fck relaps geli\u015fimi ile ili\u015fkili bulunmu\u015f (RR=0.28, %95 GA=0.01-0.29), tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan her iki rejim aras\u0131nda fark saptanmam\u0131\u015ft\u0131r (RR=0.26, %95 GA=0.01-5.42).<\/p>\n<p class=\"p3\">Solera ve arkada\u015flar\u0131n\u0131n (224) y\u00fcr\u00fctt\u00fc\u011f\u00fc randomize, a\u00e7\u0131k etiketli, \u00e7ok merkezli \u00e7al\u0131\u015fmada, toplam 194 [DOX-RIF (n=100), DOX-STREP (n=94)] hasta randomize edilmi\u015ftir. Ancak etkin bir randomizasyon y\u00f6ntemi kullan\u0131lmam\u0131\u015ft\u0131r (tek say\u0131l\u0131 ya\u015flara sahip hastalara DOX-RIF, \u00e7ift say\u0131l\u0131 ya\u015flara sahip hastalara DOX-STREP tedavisi ba\u015flanm\u0131\u015ft\u0131r). \u00c7al\u0131\u015fmada komplike olgular d\u0131\u015flanmam\u0131\u015f her iki kolda be\u015f spondilit olgusu \u00e7al\u0131\u015fmaya dahil edilmi\u015ftir. Relaps i\u00e7in takip s\u00fcresi 12 ay olarak belirlenmi\u015ftir. Hastalar\u0131n %86\u2019s\u0131 (n=167) planlanan bir y\u0131l takip s\u00fcresini tamamlam\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span> DOX-RIF kolunda 13 (%13) hasta, DOX-STREP kolunda ise 14 (%15) hastada izlem s\u00fcresi tamamlanamam\u0131\u015ft\u0131r. Her iki grupta d\u00f6rt hasta ila\u00e7 yan etkisi ve uyumsuzluk nedeniyle \u00e7al\u0131\u015fmadan d\u0131\u015flanm\u0131\u015ft\u0131r. DOX-RIF ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda DOX-STREP tedavi rejimi daha az relaps geli\u015fimi ile ili\u015fkili iken (RR=0.33, %95 GA=0.13-0.87), tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan iki tedavi rejimi aras\u0131nda farkl\u0131l\u0131k saptanmam\u0131\u015ft\u0131r (RR=0.27, %95 GA=0.06-1.22).<\/p>\n<p class=\"p3\">Hashemi ve arkada\u015flar\u0131n\u0131n (222) y\u00fcr\u00fctt\u00fc\u011f\u00fc randomize a\u00e7\u0131k, tek merkezli \u00e7al\u0131\u015fmada, toplam 219 hasta \u00fc\u00e7 farkl\u0131 tedavi grubuna [OFX-RIF (n=73), DOX-RIF (n=73), DOX-STREP (n=73)] randomize edilmi\u015ftir. Randomizasyon amac\u0131yla rastgele say\u0131lar tablosu kullan\u0131lm\u0131\u015ft\u0131r. \u00c7al\u0131\u015fmada komplike bruselloz olgular\u0131 (endokardit, spondilit, n\u00f6robruselloz), karaci\u011fer ve b\u00f6brek yetmezli\u011fi olan hastalar ve son alt\u0131 ay i\u00e7erisinde bruselloz tedavisi alan hastalar d\u0131\u015flanm\u0131\u015ft\u0131r. Relaps geli\u015fimi i\u00e7in takip s\u00fcresi alt\u0131 ay olarak belirlenmi\u015ftir. Tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 DOX-RIF kolunda 62 hastada, DOX-STREP kolunda ise 65 hastada de\u011ferlendirilmi\u015ftir. DOX-RIF ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda DOX-STREP tedavi rejimi daha az tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 ile ili\u015fkilidir (RR=0.29, %95 GA=0.08-0.99). Relaps, DOX-RIF kolunda 59, DOX-STREP kolunda ise 65 hastada de\u011ferlendirilebilmi\u015f ve her iki tedavi rejimi aras\u0131nda fark saptanmam\u0131\u015ft\u0131r (RR=0.32, %95 GA=0.09-1.12). (Bkz. Ek \u015eekil 22-24 ve Ek Tablo 13, 14)<\/p>\n<p class=\"p14\"><strong><em>G\u00fcvenlik<span class=\"Apple-converted-space\">\u00a0<\/span><\/em><\/strong><\/p>\n<p class=\"p3\">\u00d6neri ile ilgili kan\u0131tlar yedi randomize kontroll\u00fc \u00e7al\u0131\u015fmadan toplam 748 hastan\u0131n meta-analizi ile elde edilmi\u015ftir. Tedavi kesilmesine veya de\u011fi\u015ftirilmesine neden olan ciddi yan etkiler de\u011ferlendirilmeye al\u0131nm\u0131\u015ft\u0131r; DOX-RIF ve DOX-STREP tedavi rejimleri aras\u0131nda yan etki geli\u015fimi a\u00e7\u0131s\u0131ndan istatistiksel bir fark saptanmam\u0131\u015ft\u0131r (RR=0.50, %95 GA=0.13-1.93) (207-210,212,216,217).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Tedavi kesilmesine neden olan yan etki geli\u015fimi a\u00e7\u0131s\u0131ndan komplike bruselloz hastalar\u0131n\u0131n dahil edildi\u011fi (RR=0.27, %95 GA=0.03-2.34) (195,201,205,206) ve edilmedi\u011fi (RR=0.87, %95 GA=0.14-5.32) (220,223,224) \u00e7al\u0131\u015fmalarda DOX-RIF ve DOX-STREP tedavi rejimleri aras\u0131nda yan etki geli\u015fimi i\u00e7in istatistiksel fark saptanmam\u0131\u015ft\u0131r. D\u00f6rt \u00e7al\u0131\u015fmada her iki kolda hi\u00e7bir hastada tedavi kesilmesine neden olan yan etki geli\u015fimi saptanmam\u0131\u015ft\u0131r (213,219,222,223). Di\u011fer \u00fc\u00e7 \u00e7al\u0131\u015fmada DOX-RIF kolunda alt\u0131, DOX-STREP kolunda ise iki hastada tedavi, yan etki nedeniyle kesilmi\u015ftir (218,221,224). Solera ve arkada\u015flar\u0131n\u0131n (224) \u00e7al\u0131\u015fmas\u0131nda, DOX-RIF kolunda iki hastada epigastrik a\u011fr\u0131, bulant\u0131, kusma, ishal nedeniyle, bir hastada ise \u015fiddetli alerjik reaksiyon ve bir hastada ise karaci\u011fer enzimlerinde &gt;5 kat art\u0131\u015f olmas\u0131 nedeniyle; DOX-STREP kolunda ise bir hastada gastrointestinal \u015fikayetler nedeniyle tedavi kesilmi\u015ftir. Ersoy ve arkada\u015flar\u0131n\u0131n (221) \u00e7al\u0131\u015fmas\u0131nda, DOX-RIF tedavisi alan iki hastada bulant\u0131 ve kusma nedeniyle tedavi kesilmi\u015ftir. Acocella ve arkada\u015flar\u0131n\u0131n (218) \u00e7al\u0131\u015fmas\u0131nda, DOX-STREP kolunda bir hastada vertigo nedeniyle tedavi kesilmi\u015ftir.<span class=\"Apple-converted-space\">\u00a0<\/span> (Bkz. Ek \u015eekil 22-24 ve Ek Tablo 13, 14)<\/p>\n<p class=\"p3\"><strong>\u00d6nerinin Gerek\u00e7esi:<\/strong> DOX-RIF rejimi ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda relaps ve tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan DOX-STREP rejimi daha etkin bulunmu\u015ftur. Ancak etkinlik kadar tedavinin uygulanma \u015fekli ve hastan\u0131n tedaviye uyumunu etkileyecek fakt\u00f6rler de g\u00f6z \u00f6n\u00fcnde bulundurulmal\u0131d\u0131r. Streptomisin tedavisinin parenteral (intram\u00fcsk\u00fcler) uygulanma zorunlulu\u011fu hastan\u0131n tedaviye uyumunu etkileyecek \u00f6nemli bir fakt\u00f6rd\u00fcr.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> \u00c7al\u0131\u015fmalarda \u00f6rneklem say\u0131lar\u0131n\u0131n k\u00fc\u00e7\u00fck olmas\u0131 tip 2 hata olas\u0131l\u0131klar\u0131n\u0131 art\u0131rmakta ve tedavi rejimlerinin sonuca etkisini de\u011ferlendirmeyi g\u00fc\u00e7le\u015ftirmektedir. \u00c7al\u0131\u015fma pop\u00fclasyonunun birden fazla tedavi grubuna randomize edilmesi de tedavi kollar\u0131ndaki \u00f6rneklemlerin daha da k\u00fc\u00e7\u00fclmesine neden olmaktad\u0131r. Sonu\u00e7 parametrelerinin ve \u00f6zellikle relaps tan\u0131mlar\u0131n\u0131n de\u011fi\u015fken olmas\u0131 sonu\u00e7lar\u0131n yorumlanmas\u0131n\u0131 g\u00fc\u00e7le\u015ftirmektedir. Homojen hasta gruplar\u0131nda, ayn\u0131 s\u00fcreler ile uygulanan tedavi rejimlerini kar\u015f\u0131la\u015ft\u0131ran ve standart sonlam\u0131n noktalar\u0131n\u0131n tan\u0131mland\u0131\u011f\u0131 y\u00fcksek olgu say\u0131s\u0131na sahip prospektif kar\u015f\u0131la\u015ft\u0131rmal\u0131 randomize \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n<h4 class=\"p2\">8- Bruselloz tedavisinde doksisiklin + streptomisin kombinasyonu, doksisiklin + gentamisin kombinasyonundan \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><b>\u00d6neri: <\/b>Akut bruselloz tedavisinde DOX-STREP kombinasyonunun, DOX-GEN kombinasyonuna, tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, relaps ve yan etki geli\u015fimi a\u00e7\u0131s\u0131ndan \u00fcst\u00fcnl\u00fc\u011f\u00fc yoktur. Tedavide DOX ile kombinasyonda STREP veya GEN \u00f6nerilir (<i>Orta kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<\/p>\n<h4 class=\"p17\">Kan\u0131tlar\u0131n \u00d6zeti:<\/h4>\n<p class=\"p14\"><strong><em>Etkinlik<\/em><\/strong><\/p>\n<p class=\"p3\">Literat\u00fcr taramas\u0131 sonucunda DOX-STREP ve DOX-GEN kombinasyonlar\u0131n\u0131n etkinliklerinin kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131 iki randomize kontroll\u00fc \u00e7al\u0131\u015fma bulunmu\u015ftur ve 355 hastay\u0131 i\u00e7eren bu iki \u00e7al\u0131\u015fma tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, relaps ve yan etki a\u00e7\u0131s\u0131ndan meta-analizine dahil edilmi\u015ftir (225,226). Roushan ve arkada\u015flar\u0131n\u0131n (225) 2006 y\u0131l\u0131nda yay\u0131mlanan \u00e7al\u0131\u015fmas\u0131nda, hastalar, bir grup DOX (45 g\u00fcn) + STREP (14 g\u00fcn), di\u011fer grup ise DOX (45 g\u00fcn) + GEN (7 g\u00fcn) olacak \u015fekilde iki gruba randomize edilmi\u015f ve bir y\u0131l s\u00fcreyle takip edilmi\u015ftir. Her iki grupta 100\u2019er hasta \u00e7al\u0131\u015fmaya dahil edilmi\u015f ancak takipten \u00e7\u0131kan hastalar nedeniyle DOX-GEN grubunda 97, DOX-STREP grubunda ise 94 hastada analizler ger\u00e7ekle\u015ftirilmi\u015ftir. \u00c7al\u0131\u015fmaya, sakroiliit ve periferal artrit tan\u0131lar\u0131 olan hastalar dahil edilmi\u015f olmas\u0131na ra\u011fmen, spondilit veya n\u00f6robruselloz gibi komplikasyonu olan hastalar al\u0131nmam\u0131\u015ft\u0131r. Hastal\u0131k semptomlar\u0131n\u0131n ba\u015flang\u0131c\u0131ndan tan\u0131 an\u0131na kadar ge\u00e7en s\u00fcreye g\u00f6re de\u011ferlendirildi\u011finde \u00e7al\u0131\u015fmaya al\u0131nan hastalar\u0131n DOX-GEN grubunda 73 (%75.3)\u2019\u00fc, DOX-STREP grubunda ise 81 (%86.2)\u2019i akut (&lt;2 ay) olgulardan olu\u015fmaktad\u0131r. Geri kalan hastalar aras\u0131nda subakut (2 ay-1 y\u0131l) ve kronik (&gt;1 y\u0131l) olgular da mevcuttur.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Meta-analizine dahil edilen ve Roushan ve arkada\u015flar\u0131 (226) taraf\u0131ndan 2010 y\u0131l\u0131nda yay\u0131mlanan di\u011fer \u00e7al\u0131\u015fmada, hastalar, bir grup DOX (45 g\u00fcn) + STREP (14 g\u00fcn), di\u011fer grup ise DOX (8 hafta) + GEN (5 g\u00fcn) olacak \u015fekilde iki gruba randomize edilmi\u015f ve bir y\u0131l s\u00fcreyle takip edilmi\u015ftir. Her iki gruba 82 hasta al\u0131nm\u0131\u015f ve analizler bu hastalar\u0131n tamam\u0131 \u00fczerinden yap\u0131lm\u0131\u015ft\u0131r. \u00c7al\u0131\u015fmaya, sakroiliit ve periferal artrit tan\u0131lar\u0131 olan hastalar dahil edilmi\u015f olmas\u0131na ra\u011fmen, spondilit veya n\u00f6robruselloz gibi komplikasyonu olan hastalar al\u0131nmam\u0131\u015ft\u0131r.<\/p>\n<p class=\"p3\">Meta-analizi sonucunda akut bruselloz tedavisinde DOX-STREP kombinasyonunun, tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 (RR=2.03, %95 GA=0.62-6.62) ve relaps a\u00e7\u0131s\u0131ndan (RR=1.62, %95 GA=0.54-4.88) DOX-GEN kombinasyonundan \u00fcst\u00fcn olmad\u0131\u011f\u0131 bulunmu\u015ftur. (Bkz. Ek \u015eekil 25-27 ve Ek Tablo 15, 16)<\/p>\n<p class=\"p14\"><em><strong>G\u00fcvenlik<\/strong><\/em><\/p>\n<p class=\"p18\">Yan etki geli\u015fimi a\u00e7\u0131s\u0131ndan \u00e7al\u0131\u015fmalar de\u011ferlendirildi\u011finde tedavi kesmeyi gerektirecek d\u00fczeyde yan etki geli\u015fimi sadece bir \u00e7al\u0131\u015fmada (226) bildirildi\u011fi i\u00e7in meta-analizi sadece bu \u00e7al\u0131\u015fma ile yap\u0131lm\u0131\u015ft\u0131r. Akut bruselloz tedavisinde DOX-STREP kombinasyonunun, DOX-GEN kombinasyonundan, tedavi kesmeyi gerektirecek d\u00fczeyde yan etki geli\u015fmesi a\u00e7\u0131s\u0131ndan \u00fcst\u00fcn olmad\u0131\u011f\u0131 bulunmu\u015ftur (RR=2.03, %95 GA=0.62-6.62). (Bkz. Ek \u015eekil 25-27 ve Ek Tablo 15, 16)<\/p>\n<p class=\"p3\"><strong>\u00d6neri Gerek\u00e7esi:<\/strong> Streptomisin, bruselloz tedavisinde 14-21 g\u00fcn kullan\u0131lan bir aminoglikoziddir. Gentamisin, kullan\u0131m s\u00fcresi STREP\u2019e g\u00f6re daha k\u0131sa s\u00fcreli oldu\u011fundan (5-7 g\u00fcn) hasta uyumunu art\u0131rabilece\u011fi, ayr\u0131ca potansiyel yan etkiler a\u00e7\u0131s\u0131ndan daha az riske sahip olaca\u011f\u0131 i\u00e7in tedavide tercih edilebilir.<\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> Akut bruselloz tedavisinde DOX-STREP ve DOX-GEN kombinasyonlar\u0131n\u0131n etkinlik ve g\u00fcvenli\u011finin ara\u015ft\u0131r\u0131ld\u0131\u011f\u0131 ayn\u0131 merkezden \u00e7\u0131kan sadece iki randomize kontroll\u00fc \u00e7al\u0131\u015fma bulunmaktad\u0131r. Bu \u00e7al\u0131\u015fmalarda k\u00f6rlemenin yap\u0131lmam\u0131\u015f olmas\u0131 ve a\u00e7\u0131k etiketli olmalar\u0131 yanl\u0131l\u0131k riskini art\u0131ran fakt\u00f6rler olarak kar\u015f\u0131m\u0131za \u00e7\u0131kmaktad\u0131r. Ayr\u0131ca her iki \u00e7al\u0131\u015fmada GEN farkl\u0131 s\u00fcrelerde (5 veya 7 g\u00fcn) hastalara uygulanm\u0131\u015ft\u0131r. Sabit s\u00fcrelerde GEN uygulanan, farkl\u0131 merkezlerce y\u00fcr\u00fct\u00fclm\u00fc\u015f ve k\u00f6rlemenin yap\u0131ld\u0131\u011f\u0131 randomize kontroll\u00fc \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n<h4 class=\"p2\">9- Bruselloz tedavisinde kinolon grubu antimikrobik i\u00e7eren kombinasyonlar, kinolon i\u00e7ermeyen kombinasyonlardan \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><b>\u00d6neri: <\/b>Akut bruselloz tedavi rejimlerini kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n meta-analizinde, kinolon grubu antimikrobikleri i\u00e7eren kombinasyonlar\u0131n, i\u00e7ermeyen kombinasyonlara g\u00f6re, tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, relaps ve yan etki geli\u015fimi a\u00e7\u0131s\u0131ndan \u00fcst\u00fcn olmad\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Ek olarak kinolon grubu antimikrobiklerle ilgili son y\u0131llarda artan g\u00fcvenlik endi\u015feleri nedeniyle,<b> <\/b>akut bruselloz tedavisinde<b> <\/b>kinolon grubu antimikrobik i\u00e7eren kombinasyonlar\u0131n \u00f6ncelikle tercih edilmemesi \u00f6nerilir. Bruselloz tedavisinde kinolonlar\u0131n, sadece ilk se\u00e7enek ila\u00e7lar\u0131n (DOX, RIF, GEN, STREP) yan etki, ila\u00e7 etkile\u015fimi gibi herhangi bir nedenle kullan\u0131lamad\u0131\u011f\u0131 durumlarda, kombinasyonun bir bile\u015feni olarak d\u00fc\u015f\u00fcn\u00fclmesi \u00f6nerilir (<i>\u00c7ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<\/p>\n<h4 class=\"p17\">Kan\u0131tlar\u0131n \u00d6zeti:<\/h4>\n<p class=\"p14\"><em><strong>Etkinlik<\/strong><\/em><\/p>\n<p class=\"p3\">Kinolon i\u00e7eren ve i\u00e7ermeyen kombinasyonlar\u0131n kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131 toplamda 11 klinik \u00e7al\u0131\u015fma de\u011ferlendirilmi\u015ftir (214,215,221,222,227-233). S\u00f6z konusu \u00e7al\u0131\u015fmalardan \u00fc\u00e7\u00fc (230-232) randomize kontroll\u00fc olmay\u0131p g\u00f6zlemsel \u00e7al\u0131\u015fma niteli\u011findedir. Bir \u00e7al\u0131\u015fma (233) \u0130ngilizce dilinde yay\u0131mlanmam\u0131\u015f olup sadece \u0130ngilizce \u00f6zet b\u00f6l\u00fcm\u00fc vard\u0131r. Bu nedenle ara\u015ft\u0131rma sorusunun yan\u0131tlanmas\u0131 i\u00e7in meta-analizine yedi randomize kontroll\u00fc \u00e7al\u0131\u015fma (214,215,221,222, 227-229) dahil edilmi\u015ftir. Makalelerin hepsinde yanl\u0131l\u0131k riski y\u00fcksek tespit edilmi\u015ftir. \u00c7al\u0131\u015fmalar\u0131n \u00e7o\u011funda menenjit, endokardit, spondilit gibi brusellozun komplikasyonu olan hastalar \u00e7al\u0131\u015fma d\u0131\u015f\u0131 tutulmu\u015f olmas\u0131na ra\u011fmen bir \u00e7al\u0131\u015fmada (227) her bir grupta dokuzar spondilit, kal\u00e7a veya diz artriti i\u00e7eren hasta oldu\u011fu, bir di\u011fer \u00e7al\u0131\u015fmada da (229) say\u0131s\u0131 ve klinik \u00f6zellikleri a\u00e7\u0131klanmasa da \u00e7al\u0131\u015fmaya spondiliti olan hastalar\u0131n dahil edildi\u011fi anla\u015f\u0131lmaktad\u0131r. Bu nedenle sonlan\u0131m noktas\u0131 olarak tespit edilen tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, relaps ve yan etki a\u00e7\u0131s\u0131ndan meta-analizi yap\u0131l\u0131rken, kal\u00e7a, diz artriti veya spondilit hastas\u0131 i\u00e7eren bu iki makale (komplike olgular) hem ayr\u0131ca analiz edilerek hem bu iki makale hari\u00e7 tutularak (komplike olmayan olgular) alt grup analizleri ile birlikte hem de b\u00fct\u00fcn olgular\u0131 i\u00e7eren ortak bir meta-analiz ger\u00e7ekle\u015ftirilmi\u015ftir.<\/p>\n<p class=\"p3\">Meta-analizine dahil edilen Ersoy ve arkada\u015flar\u0131n\u0131n (221) \u00e7al\u0131\u015fmas\u0131nda, DOX-RIF verilen 45 hasta, DOX-STREP verilen 32 hasta ve OFX-RIF verilen 41 hasta olmak \u00fczere \u00fc\u00e7 ayr\u0131 kar\u015f\u0131la\u015ft\u0131rma grubu vard\u0131r. Bu \u00e7al\u0131\u015fma, meta-analizine dahil edilirken tedavi rejiminde kinolon i\u00e7ermeyen ilk iki grubun hasta say\u0131lar\u0131 birle\u015ftirilerek tek bir grup olarak analize dahil edilmi\u015ftir. S\u00f6z konusu \u00e7al\u0131\u015fma ile benzer tedavi gruplar\u0131 i\u00e7eren Hashemi ve arkada\u015flar\u0131n\u0131n (222) \u00e7al\u0131\u015fmas\u0131nda da ayn\u0131 birle\u015ftirme yap\u0131lm\u0131\u015f ve meta-analizine dahil edilmi\u015ftir.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Keramat ve arkada\u015flar\u0131n\u0131n (229) \u00e7al\u0131\u015fmas\u0131nda ise DOX-RIF verilen 61 hasta, CIP +RIF verilen 62 hasta ve CIP+DOX verilen 55 hasta \u00fc\u00e7 ayr\u0131 kar\u015f\u0131la\u015ft\u0131rma grubunu olu\u015fturmaktayd\u0131. Meta-analizine veriler girilirken CIP i\u00e7eren 2. ve 3. grup hastalar birle\u015ftirilerek tek bir grup olarak analize dahil edilmi\u015ftir. Kinolon i\u00e7eren ve i\u00e7ermeyen rejimlerle tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131n\u0131n de\u011ferlendirilmesinde sadece alt\u0131 \u00e7al\u0131\u015fmada bu sonlan\u0131m noktas\u0131na dair veriler olmas\u0131 nedeniyle meta-analizi bu alt\u0131 \u00e7al\u0131\u015fma ile yap\u0131lm\u0131\u015f olup 695 hastay\u0131 i\u00e7ermektedir. Akut bruselloz tedavisinde kinolon i\u00e7eren ve i\u00e7ermeyen rejimlerin hem alt grup analizinde hem de totalde, tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan birbirinden farkl\u0131 olmad\u0131klar\u0131 bulunmu\u015ftur (RR=1.03, %95 GA=0.57-1.85).<\/p>\n<p class=\"p3\">Kinolon i\u00e7eren ve i\u00e7ermeyen rejimlerin relaps oranlar\u0131 a\u00e7\u0131s\u0131ndan kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131n\u0131n meta-analizi yedi \u00e7al\u0131\u015fma kapsam\u0131nda toplam 648 hastay\u0131 i\u00e7ermektedir. Akut brusellozda kinolon i\u00e7eren ve i\u00e7ermeyen rejimlerle tedavinin, hem alt grup analizinde hem de totalde, relaps olas\u0131l\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan birbirinden farkl\u0131 olmad\u0131klar\u0131 bulunmu\u015ftur (RR=0.84, %95 GA=0.52-1.37). Keramat ve arkada\u015flar\u0131n\u0131n (229) \u00e7al\u0131\u015fmas\u0131, meta-analizinde en fazla hasta say\u0131s\u0131n\u0131n oldu\u011fu iki \u00e7al\u0131\u015fmadan biridir; 178 hasta \u00e7al\u0131\u015fmaya dahil edilmi\u015fken sadece 114 hastan\u0131n takipte relaps verileri bildirilmi\u015ftir. \u00c7al\u0131\u015fma pop\u00fclasyonu g\u00f6z \u00f6n\u00fcne al\u0131nd\u0131\u011f\u0131nda, 64 (%35) gibi \u00f6nemli say\u0131da hastan\u0131n relaps verilerini i\u00e7ermemesi \u00f6nemli bir eksiklik olarak g\u00f6r\u00fcnmektedir. \u00dc\u00e7 kollu (DOX+RIF; CIP+RIF; CIP+DOX) \u00e7al\u0131\u015fmada tedavi ba\u015far\u0131s\u0131 ve istenmeyen sonlan\u0131mlar a\u00e7\u0131s\u0131ndan bir fark g\u00f6r\u00fclmedi\u011fi bildirilmi\u015ftir. (Bkz. Ek \u015eekil 28-30 ve Ek Tablo 17, 18)<\/p>\n<p class=\"p14\"><strong><em>G\u00fcvenlik<\/em><\/strong><\/p>\n<p class=\"p3\">Yan etki bildirimleri, \u00e7al\u0131\u015fmalar\u0131n baz\u0131lar\u0131nda sadece \u201cyan etki geli\u015fti\u201d veya \u201cgeli\u015fmedi\u201d \u015feklindedir ve geli\u015fen yan etkilerin detaylar\u0131 ve tedavi kesmeye neden olup olmad\u0131klar\u0131 belirtilmemektedir. Dolay\u0131s\u0131yla bu meta-analizinde, sadece kar\u015f\u0131la\u015ft\u0131r\u0131lan tedavi rejimleri ile sonlan\u0131m noktas\u0131 olarak herhangi bir yan etkinin geli\u015fip geli\u015fmedi\u011fi al\u0131nabilmi\u015ftir. Kinolon i\u00e7eren ve i\u00e7ermeyen rejimlerin yan etki oranlar\u0131 a\u00e7\u0131s\u0131ndan kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131nda meta-analizi, yedi \u00e7al\u0131\u015fmada toplam 684 hastay\u0131 i\u00e7ermektedir. Akut brusellozda kinolon i\u00e7eren ve i\u00e7ermeyen rejimlerle tedavinin hem alt grup analizinde hem de totalde, herhangi bir yan etki geli\u015fimi a\u00e7\u0131s\u0131ndan birbirinden farkl\u0131 olmad\u0131klar\u0131 bulunmu\u015ftur (RR=0.73, %95 GA=0.43-1.25). (Bkz. Ek \u015eekil 28-30 ve Ek Tablo 17, 18)<\/p>\n<p class=\"p20\"><span class=\"s7\"><strong>\u00d6neri Gerek\u00e7esi:<\/strong> Kinolonlar yayg\u0131n olarak kullan\u0131lan antibiyotik gruplar\u0131ndand\u0131r. Tendonlar\u0131, kaslar\u0131, eklemleri, merkezi sinir sistemini i\u00e7eren ciddi yan etkilere yol a\u00e7ma potansiyeli nedeniyle Amerikan G\u0131da ve \u0130la\u00e7 Dairesi (FDA) taraf\u0131ndan <\/span><span class=\"s2\">akut bakteriyel sin\u00fczit, kronik bron\u015fitin akut bakteriyel alevlenmesi ve komplike olmayan \u00fcriner infeksiyonlarda kullan\u0131lmamas\u0131 konusunda uyar\u0131da bulunulmu\u015ftur. Belirtilen endikasyonlarda ancak alternatif tedavilerin uygulanamamas\u0131 durumlar\u0131nda uzman onay\u0131 ile kullan\u0131lmas\u0131 \u00f6nerilmektedir (234). Bruselloz tedavisinde kullan\u0131labilecek ba\u015fka temel ila\u00e7lar bulunmas\u0131 nedeniyle kinolonlar ancak bu ila\u00e7lar kullan\u0131lamad\u0131\u011f\u0131 durumlarda alternatif bir se\u00e7enek olarak d\u00fc\u015f\u00fcn\u00fclmelidir.<\/span><\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> Bu konu ile ilgili \u00e7al\u0131\u015fmalar olduk\u00e7a heterojen tedavi rejimlerinden olu\u015fmaktad\u0131r. Ayn\u0131 zamanda \u00e7al\u0131\u015fmalarda uygun randomizasyon ve k\u00f6rleme eksiktir. Tedavide temel rejim olarak kabul edilen DOX-RIF kombinasyonu ile birebir kinolonlu rejimlerin kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131, randomizasyonu ve k\u00f6rlemesi iyi planlanm\u0131\u015f, sonlan\u0131m noktalar\u0131 ve takip s\u00fcreleri uygun tan\u0131mlarla belirlenmi\u015f randomize kontroll\u00fc \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n<h4 class=\"p2\">10- Bruselloz tan\u0131s\u0131 konulmu\u015f gebelerde rifampisin + seftriakson tedavisi rifampisin + trimetoprim-s\u00fclfametoksazol tedavisine g\u00f6re daha etkili midir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Bruselloz tan\u0131s\u0131 alm\u0131\u015f gebelerin tedavisinde farkl\u0131 kombinasyonlar\u0131 kar\u015f\u0131la\u015ft\u0131ran olgu serilerinin analizinde RIF+TMP-SMX kombinasyonuyla, RIF+CRO kombinasyonu aras\u0131nda gebelik komplikasyonu geli\u015fimi a\u00e7\u0131s\u0131ndan bir fark belirlenmemi\u015ftir. Gebe bruselloz olgular\u0131n\u0131n tedavisinde RIF+TMP-SMX veya RIF+CRO kombinasyonlar\u0131ndan birinin kullan\u0131lmas\u0131 \u00f6nerilir. Ancak TMP-SMX\u2019in birinci trimesterde teratojenik etki, son trimesterde ise kernikterusa neden olma riskleri bulunmas\u0131 nedeniyle birinci ve \u00fc\u00e7\u00fcnc\u00fc trimesterde RIF+CRO kombinasyonunun tercih edilmesi \u00f6nerilir (<i>\u00c7ok<\/i> <i>d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, zay\u0131f \u00f6neri<\/i>).<\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> Gebe bruselloz olgular\u0131nda yap\u0131lm\u0131\u015f randomize kontroll\u00fc bir \u00e7al\u0131\u015fma bulunmamaktad\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>Tam metnine ula\u015f\u0131labilen, olgulara ait ayr\u0131nt\u0131l\u0131 klinik bilgilerin yer ald\u0131\u011f\u0131, 18 ya\u015f ve \u00fczeri, antepartum d\u00f6nemde tan\u0131 alm\u0131\u015f (k\u00fclt\u00fcr \u00fcremesi, STA ya da Coombs\u2019lu agl\u00fctinasyon pozitifli\u011fi ile) ve RIF+TMP-SMX ya da RIF+CRO tedavilerinden birisi bu d\u00f6nemde ba\u015flanm\u0131\u015f olan gebelerin yer ald\u0131\u011f\u0131 bir retrospektif kohort \u00e7al\u0131\u015fma, \u00fc\u00e7 olgu serisi ve 10 olgu raporu \u00e7al\u0131\u015fmaya dahil edilmi\u015ftir (235-247). Gebelik komplikasyonu geli\u015ftikten sonra bruselloz tan\u0131s\u0131 ya da tedavisi alan, tedavi almayan, 18 ya\u015f alt\u0131 ya da klinik verilerine ula\u015f\u0131lamayan hastalar \u00e7al\u0131\u015fmaya dahil edilmemi\u015ftir. Primer sonlan\u0131m gebelik komplikasyonu geli\u015fimi olup bunlar; spontan <i>abortus<\/i>, preterm eylem, intrauterin fetal \u00f6l\u00fcm ve uzam\u0131\u015f membran r\u00fcpt\u00fcr\u00fcd\u00fcr.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Analize dahil edilen ve ayr\u0131nt\u0131l\u0131 klinik verilerine ula\u015f\u0131labilen 146 hastadan olu\u015fan gebe bruselloz kohortu olu\u015fturulmu\u015ftur. Hastalar\u0131n 67 (%45.9)\u2019sinde RIF+TMP-SMX, 79 (%54.1)\u2019unda RIF+CRO kombinasyonu kullan\u0131lm\u0131\u015ft\u0131r. Toplamda 146 gebenin 58 (%45.9)\u2019inde gebelik komplikasyonu geli\u015fmi\u015f olup en s\u0131k g\u00f6r\u00fclen preterm eylemdir. Hastalar\u0131n takip s\u00fcreleri de\u011fi\u015fken olmakla birlikte hastalar\u0131n \u00fc\u00e7\u00fcnde relaps geli\u015fti\u011fi bildirilmi\u015ftir. Gebelik komplikasyonu geli\u015fimini etkileyen de\u011fi\u015fkenler analiz edildi\u011finde iki grup aras\u0131nda tek anlaml\u0131 farkl\u0131l\u0131k gebelik haftas\u0131nda g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (<i>p<\/i>=0.029). RIF+TMP-SMX tedavisi alan gebelerin 24 (%35,8)\u2019\u00fcnde, RIF+CRO tedavisi alanlar\u0131n ise 34 (%43)\u2019\u00fcnde gebelik komplikasyonu izlenmi\u015ftir (<i>p<\/i>=0.375). Aradaki fark istatistiksel olarak anlaml\u0131 d\u00fczeyde bulunmam\u0131\u015ft\u0131r. (Bkz. Ek Tablo 19, 20)<\/p>\n<p class=\"p3\"><strong>G\u00fcvenlilik:<\/strong> G\u00fcvenlilik konusunda da fet\u00fcste antimikrobiyallere ba\u011fl\u0131 geli\u015febilecek yan etkiler ile ilgili net veri sunan bir \u00e7al\u0131\u015fma bulunmamaktad\u0131r. \u00c7al\u0131\u015fmalar\u0131n \u00e7o\u011funda TMP-SMX fetal kernikterus riski nedeni ile \u00fc\u00e7\u00fcnc\u00fc trimesterde tercih edilmemi\u015ftir. (Bkz. Ek Tablo 19, 20)<\/p>\n<p class=\"p3\"><strong>\u00d6neri Gerek\u00e7esi:<\/strong> Bruselloz tedavisinde kullan\u0131lan TET, aminoglikozit ve kinolon grubu antibiyotiklerin gebelerde kullan\u0131lamamas\u0131 nedeni ile olduk\u00e7a s\u0131n\u0131rl\u0131 tedavi se\u00e7ene\u011fi bulunmaktad\u0131r. Kullan\u0131labilecek ila\u00e7lar TMP-SMX, RIF ve CRO\u2019dur. Gebe bruselloz hastalar\u0131n\u0131n takibinde; hastal\u0131\u011f\u0131n erken tan\u0131nmas\u0131 ve komplikasyon geli\u015fimini en aza indirgeyecek \u015fekilde uygun tedavilerin erkenden ba\u015flanmas\u0131 en \u00f6nemli noktad\u0131r. RIF+TMP-SMX ve RIF+CRO kombinasyonlar\u0131 gebelik komplikasyonu geli\u015fimi a\u00e7\u0131s\u0131ndan benzer \u00f6zellikte olup gebe bruselloz olgular\u0131nda kullan\u0131labilir. TMP-SMX\u2019in birinci trimesterde teratojenite, \u00fc\u00e7\u00fcnc\u00fc trimesterde ise kernikterus riski nedeni ile kullan\u0131m\u0131na dikkat edilmelidir. Bu d\u00f6nemlerde alternatif olarak RIF+CRO kombinasyonu tercih edilebilir.<\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> \u0130yi planlanm\u0131\u015f, prospektif \u00e7al\u0131\u015fmalar\u0131n yoklu\u011fu nedeni ile gebelerde bruselloz tedavisi ile ilgili mevcut bilgiler genellikle g\u00f6zlemsel \u00e7al\u0131\u015fmalardan ve olgu raporlar\u0131ndan elde edilmi\u015ftir. Yap\u0131lan \u00e7al\u0131\u015fmalar\u0131n pek \u00e7o\u011fu brusellozun gebelik komplikasyonlar\u0131 \u00fczerindeki etkisini de\u011ferlendirmeye y\u00f6nelik oldu\u011fu i\u00e7in tedavi ile ilgili veriler k\u0131s\u0131tl\u0131d\u0131r. Bu nedenle bu veriler \u00fczerinden tedavi rejiminin klinik sonlan\u0131m \u00fczerindeki etkisini de\u011ferlendirmek yan\u0131lt\u0131c\u0131 olabilir. G\u00fcvenlilik konusunda da fet\u00fcste antimikrobiyallere ba\u011fl\u0131 geli\u015febilecek yan etkiler ile ilgili net veri sunan bir \u00e7al\u0131\u015fma bulunmamaktad\u0131r. Bu konuda ileri \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n<h4 class=\"p2\">11- N\u00f6robruselloz tedavisinde seftriakson i\u00e7eren kombinasyon rejimi, seftriakson i\u00e7ermeyen rejime g\u00f6re daha etkili midir?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> Tedavi rejimlerini kar\u015f\u0131la\u015ft\u0131ran n\u00f6robruselloz olgu serilerinin IPD meta-analizinde tedaviye CRO eklenmesinin tedavi ba\u015far\u0131s\u0131n\u0131 anlaml\u0131 olarak art\u0131rd\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. N\u00f6robruselloz tedavisinde standart tedaviye CRO eklenmesi \u00f6nerilir (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> Literat\u00fcrde tespit edilen 189 n\u00f6robruselloz olgusu kapsam\u0131nda ayr\u0131nt\u0131l\u0131 klinik verilerine ula\u015f\u0131labilen 121 olgunun analizi yap\u0131lm\u0131\u015ft\u0131r (41,208,248-263). Hastalar\u0131n 63 (%48)\u2019\u00fcn\u00fcn tedavileri CRO i\u00e7erirken, 58 (%42)\u2019inin tedavileri CRO i\u00e7ermiyordu. Seftriakson i\u00e7eren tedavi rejimi alan hastalar\u0131n 52 (%68)\u2019sinde tam iyile\u015fme (\u00f6l\u00fcm, relaps ve sekel olmamas\u0131) g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (Bkz. Ek Tablo 21, 22).<\/p>\n<p class=\"p3\">\u00c7ok de\u011fi\u015fkenli analizde, n\u00f6robrusellozda tedaviye CRO eklenmesi (OR=7.48, %95 GA=3.19-17.53; <i>p<\/i>&lt;0.001) tam iyile\u015fmeye etki eden en \u00f6nemli fakt\u00f6r olarak saptanm\u0131\u015ft\u0131r. N\u00f6robrusellozda standart tedaviye CRO eklenmelidir (Bkz. Ek Tablo 23).<\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> Literat\u00fcrde n\u00f6robruselloz tedavisi ile ilgili veriler olgu sunumlar\u0131 ve retrospektif \u00e7al\u0131\u015fmalarla s\u0131n\u0131rl\u0131d\u0131r. Bu konu ile ilgili \u00e7al\u0131\u015fmalar olduk\u00e7a heterojen tedavi rejimlerinden olu\u015fmaktad\u0131r. Tedavide temel rejim olarak kabul edilen DOX-RIF kombinasyonu ile bu tedaviye CRO eklenmesinin klinik ba\u015far\u0131ya etkisinin ara\u015ft\u0131ralaca\u011f\u0131 randomize kontroll\u00fc \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n<p class=\"p3\"><strong>\u00d6nerinin Gerek\u00e7esi:<\/strong> N\u00f6robrusellozda DOX-RIF tedavisine CRO eklenmesiyle ba\u015far\u0131l\u0131 sonu\u00e7lara ula\u015fmak m\u00fcmk\u00fcnd\u00fcr.<\/p>\n<h4 class=\"p2\">12- <i>Brucella <\/i>spp. endokarditi olan hastalarda, tan\u0131 an\u0131ndaki Wright STA testi titresi olumsuz sonu\u00e7lar\u0131 g\u00f6sterir mi?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp.<b> <\/b>endokarditi olgular\u0131n\u0131n IPD meta-analizinde, tan\u0131 an\u0131ndaki Wright agl\u00fctinasyon titresinin 1\/1280\u2019in \u00fczerinde olmas\u0131n\u0131n, \u00f6l\u00fcm riskini belirgin olarak art\u0131rd\u0131\u011f\u0131 belirlenmi\u015ftir. <i>Brucella<\/i> spp. endokarditi olan hastalarda, tan\u0131 an\u0131ndaki Wright STA testi titresinin 1\/1280\u2019in \u00fczerinde olmas\u0131n\u0131n \u00f6l\u00fcm riskinin y\u00fcksek olabilece\u011fini \u00f6ng\u00f6rmek a\u00e7\u0131s\u0131ndan kullan\u0131m\u0131 d\u00fc\u015f\u00fcn\u00fclebilir (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, zay\u0131f \u00f6neri<\/i>).<\/p>\n<p class=\"p3\"><span class=\"s2\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> Seksen alt\u0131 \u00e7al\u0131\u015fmada yer alan<b> <\/b>273 <i>Brucella <\/i>spp. endokarditi olgusunu i\u00e7eren IPD meta-analizi \u00e7al\u0131\u015fmas\u0131nda (264-349), ba\u015fvuruda Wright agl\u00fctinasyon titresi bilinen 227 hastada mortaliteye etki eden risk fakt\u00f6rlerinin tek de\u011fi\u015fkenli analizinde, ba\u015fvurudaki Wright agl\u00fctinasyon titresi &gt;1\/1280 olan hastalarda mortalite oran\u0131 (15\/90, %16.6), olmayanlardan (12\/137, %8.75) daha y\u00fcksek bulunmu\u015ftur (<i>p<\/i>=0.072). Ayn\u0131 verilerin \u00e7ok de\u011fi\u015fkenli analizinde de ba\u015fvurudaki Wright agl\u00fctinasyon titresinin &gt;1\/1280 olmas\u0131, \u00f6l\u00fcm\u00fc g\u00f6steren ba\u011f\u0131ms\u0131z bir risk fakt\u00f6r\u00fc olarak tan\u0131mlanm\u0131\u015ft\u0131r (OR=7.01, %95 GA=1.96-24.99). Tan\u0131 an\u0131ndaki Wright STA testi titresinin &gt;1\/1280 olmas\u0131 \u00f6l\u00fcm d\u0131\u015f\u0131 istenmeyen sonlan\u0131mlar i\u00e7in de tek de\u011fi\u015fkenli analizlerde risk fakt\u00f6r\u00fc olarak tan\u0131mlanm\u0131\u015ft\u0131r [15\/81 (%18.51)\u2019e kar\u015f\u0131l\u0131k 10\/132 (%7.57); <i>p<\/i>=0.016].<span class=\"Apple-converted-space\">\u00a0 <\/span>(Bkz. Ek \u015eekil 31 ve Ek Tablo 24-31)<\/span> <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong>\u00d6nerinin Gerek\u00e7esi:<\/strong> Bruselloz klinik g\u00f6r\u00fcn\u00fcmleri i\u00e7inde en s\u0131k \u00f6l\u00fcme neden olan klinik tablo infektif endokardittir. Bu nedenle <i>Brucella <\/i>spp.\u2019ye ba\u011fl\u0131 infektif endokardit geli\u015fen hastalarda mortaliteyi \u00f6ng\u00f6rd\u00fcrecek prognostik, \u00f6l\u00e7\u00fclebilir fakt\u00f6rlerin tan\u0131mlanmas\u0131, \u00f6l\u00fcm\u00fc azaltabilecek etkili \u00f6nlemlerin erkenden al\u0131nmas\u0131na olanak tan\u0131yabilir. Ba\u015fvuru an\u0131ndaki Wright STA testi titresi, t\u00fcm hastalarda kolayca bak\u0131labilen, kolay uygulanabilen bir test olmas\u0131 ve hem \u00f6l\u00fcm\u00fc hem de \u00f6l\u00fcm d\u0131\u015f\u0131 istenmeyen sonlan\u0131mlar\u0131 \u00f6ng\u00f6rd\u00fcrebilece\u011fine dair kan\u0131tlar elde edilmi\u015f olmas\u0131 nedeniyle, <i>Brucella<\/i> spp.\u2019ye ba\u011fl\u0131 endokardit tan\u0131s\u0131 konulan hastalarda tedavi \u00f6ncesi bak\u0131larak prognostik de\u011ferlendirmede kullan\u0131labilece\u011fi d\u00fc\u015f\u00fcn\u00fclm\u00fc\u015ft\u00fcr.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> <i>Brucella <\/i>spp.\u2019ye ba\u011fl\u0131 endokardit olgular\u0131nda tan\u0131 an\u0131ndaki Wright STA testi titresinin prognostik de\u011ferini ara\u015ft\u0131ran prospektif bir g\u00f6zlemsel \u00e7al\u0131\u015fma bulunamam\u0131\u015ft\u0131r. Var olan kan\u0131tlar tek olgu veya \u00e7oklu olgu serilerinin IPD meta-analiziyle elde edilmi\u015ftir. <i>Brucella <\/i>spp.\u2019ye ba\u011fl\u0131 endokardit tan\u0131mlanm\u0131\u015f hastalarda prognoza etki edecek fakt\u00f6rleri analiz edecek \u00fclke \u00e7ap\u0131nda yap\u0131lacak prospektif, \u00e7ok merkezli, kohort \u00e7al\u0131\u015fmalara gereksinim vard\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h4 class=\"p2\">13- <i>Brucella <\/i>spp. endokarditi olan hastalarda, 3\u2019l\u00fc antimikrobik tedavi rejimleri, 2\u2019li antimikrobik tedavi rejimlerinden daha \u00fcst\u00fcn m\u00fcd\u00fcr?<span class=\"Apple-converted-space\">\u00a0<\/span><\/h4>\n<p class=\"p3\"><strong>\u00d6neri: <\/strong><i>Brucella<\/i> spp.<b> <\/b>endokarditi olgular\u0131n\u0131n IPD meta-analizinde, 2\u2019li antimikrobik tedavi alanlarda \u00f6l\u00fcm oran\u0131, istatistiksel olarak anlaml\u0131 olmasa da 3\u2019l\u00fc tedavi alanlardan daha y\u00fcksek bulunmu\u015ftur.<span class=\"Apple-converted-space\">\u00a0 <\/span>\u00d6l\u00fcm d\u0131\u015f\u0131 istenmeyen etkiler birle\u015fik sonlan\u0131m\u0131 (rek\u00fcrans veya istenmeyen ila\u00e7 etkileri veya yeniden hastane yat\u0131\u015f\u0131 veya hastane yat\u0131\u015f\u0131nda postoperatif komplikasyonlar veya bir y\u0131l i\u00e7inde yeniden ameliyat edilme) 2\u2019li antimikrobik tedavi alanlarda 3\u2019l\u00fc tedavi alanlardan anlaml\u0131 olarak daha y\u00fcksek bulunmu\u015ftur. Bir di\u011fer komplike bruselloz tablosu olan spondilodiskit konusunda yap\u0131lm\u0131\u015f \u00e7al\u0131\u015fmalar\u0131n, bu rehber \u00e7al\u0131\u015fmas\u0131 s\u0131ras\u0131nda yap\u0131lan meta-analizinde de 3\u2019l\u00fc tedaviler daha \u00fcst\u00fcn bulunmu\u015ftur (bak\u0131n\u0131z 18 numaral\u0131 PICO sorusu). <i>Brucella <\/i>spp. endokarditi olgular\u0131n\u0131n tedavisinde 3\u2019l\u00fc antimikrobik tedavi rejimleri \u00f6nerilir (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<span class=\"Apple-converted-space\">\u00a0 \u00a0<\/span><\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> Seksen alt\u0131 \u00e7al\u0131\u015fmada yer alan<b> <\/b>273 <i>Brucella<\/i> spp. endokarditi olgusunu i\u00e7eren IPD meta-analizinde (264-349) 2\u2019li tedavi alan hastalar\u0131n 7\/52 (%13.46)\u2019si \u00f6lm\u00fc\u015fken, 3\u2019l\u00fc tedavi alan hastalar\u0131n %11.36\u2019s\u0131n\u0131n \u00f6ld\u00fc\u011f\u00fc belirlenmi\u015ftir (<i>p<\/i>=0.634).<span class=\"Apple-converted-space\">\u00a0 <\/span>Ayn\u0131 analizde di\u011fer istenmeyen sonlan\u0131mlar (rek\u00fcrans veya istenmeyen ila\u00e7 etkileri veya yeniden hastane yat\u0131\u015f\u0131 veya hastane yat\u0131\u015f\u0131nda postoperatif komplikasyonlar veya bir y\u0131l i\u00e7inde yeniden ameliyat edilme) 2\u2019li tedavi alanlar\u0131n %20.4\u2019\u00fcnde g\u00f6r\u00fclm\u00fc\u015fken, 3\u2019l\u00fc tedavi alanlar\u0131n %9.8\u2019inde g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (<i>p<\/i>=0.038). (Bkz. Ek Tablo 24, 25, 27-29, 32, 33)<\/p>\n<p class=\"p3\"><strong>\u00d6nerinin Gerek\u00e7esi:<\/strong> Brusellozun en \u00f6l\u00fcmc\u00fcl \u015fekli olan endokarditli olgularda gerek \u00f6l\u00fcm\u00fc gerekse \u00f6l\u00fcm d\u0131\u015f\u0131 di\u011fer istenmeyen sonlan\u0131mlar\u0131 azaltabilecek m\u00fcdahaleler olduk\u00e7a \u00f6nemlidir. <i>Brucella <\/i>spp.\u2019ye ba\u011fl\u0131 endokardit olgular\u0131nda, cerrahi m\u00fcdahalenin yan\u0131nda di\u011fer \u00f6nemli bile\u015fen olan antimikrobiyal tedavinin etkili olmas\u0131 \u00e7ok kritiktir. Ge\u00e7mi\u015f y\u0131llarda sunulmu\u015f tek olgu veya olgu serilerinde yer alan <i>Brucella<\/i> spp. endokardit olgular\u0131na ait verilerin IPD-meta-analizinde istatistiksel olarak anlaml\u0131 olmasa da say\u0131sal olarak \u00f6l\u00fcm oran\u0131n\u0131n daha az g\u00f6r\u00fclm\u00fc\u015f olmas\u0131, di\u011fer istenmeyen sonlan\u0131mlar\u0131n 3\u2019l\u00fc tedavi alan grupta belirgin olarak daha az g\u00f6r\u00fclmesi ve ayr\u0131ca endokardit gibi bir di\u011fer komplike bruselloz tablosu olan spondilodiskit olgular\u0131yla ilgili yap\u0131lm\u0131\u015f klinik ara\u015ft\u0131rmalar\u0131n meta-analizinde 3\u2019l\u00fc tedavilerin daha etkili bulunmu\u015f olmas\u0131 nedenleriyle endokardit olgular\u0131nda da 3\u2019l\u00fc antimikrobik tedavi kombinasyonlar\u0131n\u0131n kullan\u0131m\u0131 \u00f6nerilmi\u015ftir.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131: <\/strong><i>Brucella <\/i>spp.\u2019ye ba\u011fl\u0131 endokarditi olan hastalarda 2\u2019li veya 3\u2019l\u00fc antimikrobik tedavi kombinasyonlar\u0131n\u0131n etkinli\u011fini ve g\u00fcvenilirli\u011fini kar\u015f\u0131la\u015ft\u0131ran g\u00f6zlemsel veya randomize kontroll\u00fc bir klinik ara\u015ft\u0131rma yoktur. <i>Brucella <\/i>spp. endokarditlerinde 2\u2019li ve 3\u2019l\u00fc antimikrobik tedavi kombinasyonlar\u0131n\u0131n etkinli\u011fini ve g\u00fcvenilirli\u011fini ara\u015ft\u0131ran, \u00fclke \u00e7ap\u0131nda yap\u0131lacak g\u00f6zlemsel ve randomize kontroll\u00fc klinik \u00e7al\u0131\u015fmalara gereksinim vard\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h4 class=\"p2\"><b>1<\/b>4-<i> Brucella<\/i> spp. endokarditi olan hastalarda aminoglikozid i\u00e7eren ve i\u00e7ermeyen tedaviler aras\u0131nda olumsuz sonu\u00e7lar a\u00e7\u0131s\u0131ndan fark var m\u0131d\u0131r?<\/h4>\n<p class=\"p18\"><b>\u00d6neri:<\/b> <i>Brucella<\/i> spp. endokarditi olgular\u0131n\u0131n IPD meta-analizinde, aminoglikozid i\u00e7eren rejimlerle tedavi edilenlerde \u00f6l\u00fcm oran\u0131 belirgin olarak daha d\u00fc\u015f\u00fck tespit edilmekle birlikte ba\u015fta istenmeyen ila\u00e7 etkileri olmak \u00fczere, \u00f6l\u00fcm d\u0131\u015f\u0131 istenmeyen sonlan\u0131mlar\u0131n geli\u015fme riski de belirgin olarak daha y\u00fcksek bulunmu\u015ftur. <i>Brucella<\/i> spp. endokarditlerinde aminoglikozid i\u00e7eren rejimlerle tedavi \u00f6nerilir, ancak aminoglikozid verilen hastalarda, nefrotoksisite y\u00f6n\u00fcnden yak\u0131n izlem yap\u0131lmal\u0131, ek nefrotoksik ajanlar\u0131n kullan\u0131m\u0131ndan ka\u00e7\u0131n\u0131lmal\u0131d\u0131r (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><span class=\"s2\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> <i>Brucella <\/i>spp.\u2019ye ba\u011fl\u0131 endokardit olgu sunumu veya olgu serilerini i\u00e7eren toplam 86 yay\u0131ndaki (264-349) 273 hasta verisiyle yap\u0131lan IPD meta-analizinde, tek de\u011fi\u015fkenli analizde, aminoglikozid i\u00e7eren rejimlerle tedavi yap\u0131lanlarda \u00f6l\u00fcm oran\u0131 [10\/123 (%8.1)], aminoglikozid i\u00e7eren rejimlerle tedavi edilmeyenlerden [22\/147 (%14.9)] daha d\u00fc\u015f\u00fck bulunmu\u015ftur (<i>p<\/i>=0.084). Yukar\u0131da s\u00f6z edilen IPD meta-analizinin \u00e7ok de\u011fi\u015fkenli analizinde de tedavide aminoglikozid i\u00e7eren rejimlerin kullan\u0131lmas\u0131 \u00f6l\u00fcm riskini azaltan ba\u011f\u0131ms\u0131z bir risk fakt\u00f6r\u00fc olarak tan\u0131mlanm\u0131\u015ft\u0131r (OR=0.250, %95 GA=0.075-0.831; <i>p<\/i>=0.024). Ayn\u0131 \u00e7al\u0131\u015fmada tek de\u011fi\u015fkenli analizlerde aminoglikozid i\u00e7eren rejimler kullan\u0131lan hastalarda, kullanmayanlara g\u00f6re \u00f6l\u00fcm d\u0131\u015f\u0131 istenmeyen sonlan\u0131mlar\u0131n (rek\u00fcrans veya istenmeyen ila\u00e7 etkileri veya yeniden hastane yat\u0131\u015f\u0131 veya hastane yat\u0131\u015f\u0131nda postoperatif komplikasyonlar veya bir y\u0131l i\u00e7inde yeniden ameliyat edilme) daha fazla g\u00f6r\u00fcld\u00fc\u011f\u00fc saptanm\u0131\u015f [%19.7\u2019ye kar\u015f\u0131l\u0131k %5.1; <i>p<\/i>&lt;0.001] ve fark\u0131n \u00f6zellikle ila\u00e7 istenmeyen etkilerinden [%7.8\u2019e kar\u015f\u0131l\u0131k %0.7; <i>p<\/i>=0.006] kaynakland\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. \u00c7ok de\u011fi\u015fkenli analizlerde de aminoglikozid i\u00e7eren tedavilerin kullan\u0131lmas\u0131, \u00f6l\u00fcm d\u0131\u015f\u0131 istenmeyen sonlan\u0131mlar a\u00e7\u0131s\u0131ndan riski art\u0131ran ba\u011f\u0131ms\u0131z bir risk fakt\u00f6r\u00fc olarak saptanm\u0131\u015ft\u0131r (OR=2.84, %95 GA=1.06-7.58; <i>p<\/i>=0.036). (Bkz. Ek Tablo 24, 25, 27-29, 34, 35)<\/span><\/p>\n<p class=\"p3\"><strong>\u00d6nerinin Gerek\u00e7esi:<\/strong> Brusellozun en \u00f6l\u00fcmc\u00fcl komplikasyonu olan endokarditin geli\u015fti\u011fi olgularda, tedavinin cerrahiyle birlikte ana bile\u015feni olan antimikrobiyal tedavinin optimizasyonu olduk\u00e7a \u00f6nemlidir. Mevcut veriler, aminoglikozid i\u00e7eren tedavi rejimlerinin endokarditli olgularda \u00f6l\u00fcm\u00fc azalt\u0131rken, ba\u015fta istenmeyen ila\u00e7 etkileri olmak \u00fczere daha fazla istenmeyen olaylara yol a\u00e7t\u0131\u011f\u0131n\u0131 d\u00fc\u015f\u00fcnd\u00fcrmektedir. Komplike olmayan bruselloz olgular\u0131n\u0131n tedavisini kar\u015f\u0131la\u015ft\u0131ran g\u00f6zlemsel ve randomize kontroll\u00fc \u00e7al\u0131\u015fmalar\u0131n, bu rehber \u00e7al\u0131\u015fmas\u0131 i\u00e7in yap\u0131lan meta-analizinde de aminoglikozid i\u00e7eren rejimlerde tedavi ba\u015far\u0131s\u0131n\u0131n daha y\u00fcksek oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (bak\u0131n\u0131z 7 numaral\u0131 PICO sorusu). <i>Brucella<\/i> spp.\u2019ye ba\u011fl\u0131 endokardit olgular\u0131n\u0131n antimikrobiyal tedavisinde de aminoglikozid i\u00e7eren rejimlerin kullan\u0131m\u0131 \u00f6nerilmi\u015ftir. Ancak aminoglikozidlerin ba\u015fta nefro\/ototoksik etkileri gibi gayet iyi tan\u0131mlanm\u0131\u015f istenmeyen etkilerinin, di\u011fer antimikrobiklerden daha fazla olabilece\u011fi de burada yap\u0131lm\u0131\u015f analizlerde g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Bu nedenle aminoglikozid ba\u015flanan hastalarda istenmeyen etkilerin yak\u0131ndan izleminin ve aminoglikozidlerle benzer istenmeyen etki profili olan ve endokardit gibi kardiyak sorunu olan hastalarda s\u0131kl\u0131kla kullan\u0131labilen ba\u015fta di\u00fcretikler gibi ila\u00e7lar\u0131n birlikte kullan\u0131m\u0131ndan m\u00fcmk\u00fcn oldu\u011funca ka\u00e7\u0131n\u0131lmas\u0131 gerekti\u011fi de vurgulanm\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> <i>Brucella <\/i>spp.\u2019ye ba\u011fl\u0131 endokarditi olan hastalarda aminoglikozid i\u00e7eren ve i\u00e7ermeyen tedavi kombinasyonlar\u0131n\u0131n etkinli\u011fini ve g\u00fcvenilirli\u011fini kar\u015f\u0131la\u015ft\u0131ran g\u00f6zlemsel veya randomize kontroll\u00fc klinik ara\u015ft\u0131rmalar yoktur. <i>Brucella <\/i>spp. endokarditlerinde STREP veya GEN i\u00e7eren veya i\u00e7ermeyen tedavi kombinasyonlar\u0131n\u0131n etkinli\u011fini ve g\u00fcvenilirli\u011fini ara\u015ft\u0131ran, \u00fclke \u00e7ap\u0131nda yap\u0131lacak g\u00f6zlemsel ve randomize kontroll\u00fc klinik \u00e7al\u0131\u015fmalara gereksinim vard\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h4 class=\"p2\"><b>15- <i>Brucella <\/i>Spp. endokarditi olan hastalarda kapak cerrahisi uygulamas\u0131n\u0131n olumsuz sonu\u00e7lar\u0131 azaltmada etkisi var m\u0131d\u0131r?<\/b><\/h4>\n<p class=\"p18\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp.<b> <\/b>endokarditi olgular\u0131n\u0131n IPD meta-analizinde, kapak cerrahisi uygulanmas\u0131n\u0131n \u00f6l\u00fcm riskini belirgin olarak azaltt\u0131\u011f\u0131 belirlenmi\u015ftir. <i>Brucella<\/i> spp. endokarditi tan\u0131s\u0131 konulan hastalarda, \u0130nfektif Endokardit Ekibi taraf\u0131ndan acil veya elektif kapak cerrahisi indikasyonlar\u0131 dikkatle de\u011ferlendirilerek, uygun bulunan hastalarda cerrahinin yap\u0131lmas\u0131 \u00f6nerilir (<i>D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri<\/i>).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> <i>Brucella <\/i>spp.\u2019ye ba\u011fl\u0131 endokardit olgu sunumu veya olgu serilerini i\u00e7eren toplam 86 yay\u0131ndaki (264-349) 273 hasta verisiyle yap\u0131lan IPD meta-analizinde, mortaliteye etki eden risk fakt\u00f6rlerinin tek de\u011fi\u015fkenli analizinde, kapak cerrahisi yap\u0131lanlarda \u00f6l\u00fcm oran\u0131, yap\u0131lmayanlardan belirgin olarak daha d\u00fc\u015f\u00fck bulunmu\u015ftur [10\/184 (%5.4)\u2019e kar\u015f\u0131l\u0131k 22\/86 (%25.5); <i>p<\/i>&lt;0.001].<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Ayn\u0131 \u015fekilde \u00e7ok de\u011fi\u015fkenli analizlerde de kapak cerrahisi yap\u0131lmas\u0131 \u00f6l\u00fcm\u00fc azaltan ba\u011f\u0131ms\u0131z fakt\u00f6r olarak tan\u0131mlanm\u0131\u015ft\u0131r (OR=0.068, %95 GA=0.019-0.237). (Bkz. Ek Tablo 24, 25, 27-29, 36)<\/p>\n<p class=\"p3\"><strong>\u00d6nerinin Gerek\u00e7esi:<\/strong> \u0130nfektif endokardit geli\u015fmi\u015f hastalarda etkenden ba\u011f\u0131ms\u0131z olarak, akut kalp yetmezli\u011fine yol a\u00e7acak kapak yetmezli\u011fi geli\u015fmi\u015fse acilen, <span class=\"s8\">kontrol edilemeyen lokal (apse, fist\u00fcl, anevrizma vb.) veya sistemik infeksiyon (kan k\u00fclt\u00fcrlerinin negatifle\u015fmemesi veya ate\u015fin d\u00fc\u015fmemesi ve ba\u015fka bir kaynak bulunamamas\u0131), yineleyen embolizm, b\u00fcy\u00fck vejetasyon veya ileri sol kalp kapa\u011f\u0131 yetersizli\u011fi veya darl\u0131\u011f\u0131 olmas\u0131 halinde erken kapak ameliyat\u0131 \u00f6nerilir. <\/span>Bunlara ek olarak tedavisi g\u00fc\u00e7 olan mikroorganizmalar s\u00f6z konusuysa da cerrahinin \u00f6ncelenmesi tavsiye edilmektedir. <i>Brucella<\/i> spp., \u00f6zellikle h\u00fccre i\u00e7inde de yerle\u015febilmesi nedeniyle tedavisi g\u00fc\u00e7 mikroorganizmalar grubunda yer almaktad\u0131r ve bu nedenle de eskiden beri endokarditli olgularda kapak cerrahisinin s\u0131kl\u0131kla gerekece\u011fi ve yap\u0131lmas\u0131n\u0131n iyi olaca\u011f\u0131 uzman g\u00f6r\u00fc\u015f\u00fc olarak bildirilmektedir (350). Seksen alt\u0131 \u00e7al\u0131\u015fmada yer alan 273 bruselloz olgusunu de\u011ferlendirdi\u011fimiz IPD meta-analizinde endokardit tan\u0131s\u0131 konulmu\u015f olgulardan kapak ameliyat\u0131 yap\u0131lanlarda mortalitenin belirgin olarak daha az g\u00f6r\u00fcld\u00fc\u011f\u00fc ve cerrahi uygulanmas\u0131n\u0131n mortaliteyi belirgin olarak azaltan en \u00f6nemli fakt\u00f6r oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella <\/i>spp.\u2019ye ba\u011fl\u0131 endokarditi olan <span class=\"s8\">hastalarda acil veya elektif kalp kapak ameliyat\u0131 indikasyonlar\u0131n\u0131n \u0130nfektif Endokardit Ekibi taraf\u0131ndan dikkatle de\u011ferlendirilmesi ve bu hastalarda indikasyon varl\u0131\u011f\u0131nda cerrahinin geciktirilmeden yap\u0131lmas\u0131, mortalitenin azalt\u0131lmas\u0131 a\u00e7\u0131s\u0131ndan \u00f6nemlidir.<span class=\"Apple-converted-space\">\u00a0<\/span><\/span><\/p>\n<p class=\"p21\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> <i>Brucella<\/i> spp. endokarditi olan hastalarda kapak cerrahisi yap\u0131lmas\u0131n\u0131n, \u00f6l\u00fcm ve di\u011fer istenmeyen sonlan\u0131mlar \u00fczerine etkisini ara\u015ft\u0131ran randomize, kontroll\u00fc \u00e7al\u0131\u015fmalara gereksinim vard\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h4 class=\"p2\"><b>1<\/b>6-<i> Brucella<\/i> spp. endokarditi olan hastalarda \u22643 ayl\u0131k antimikrobiyal tedaviler ile &gt;3 ayl\u0131k tedaviler aras\u0131nda olumsuz sonu\u00e7lar a\u00e7\u0131s\u0131ndan fark var m\u0131d\u0131r?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp.<b> <\/b>endokarditi olgular\u0131n\u0131n IPD meta-analizinde, \u00f6len hastalar\u0131n hemen hepsinin ilk \u00fc\u00e7 ayda \u00f6lm\u00fc\u015f oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Bu nedenle tedavi s\u00fcresinin \u00f6l\u00fcm \u00fczerine etkisi belirlenememi\u015ftir. Ayn\u0131 analizde &gt;3 ay tedavi alan ve almayan hastalar aras\u0131nda \u00f6l\u00fcm d\u0131\u015f\u0131 istenmeyen sonlan\u0131mlar\u0131n s\u0131kl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan bir fark bulunamam\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>Bilgi bo\u015flu\u011fu nedeniyle \u00f6neri yap\u0131lamaz (<i>Bilgi bo\u015flu\u011fu<\/i>).<\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti: <\/strong><i>Brucella <\/i>spp.\u2019ye ba\u011fl\u0131 endokardit olgu sunumu veya olgu serilerini i\u00e7eren toplam 86 yay\u0131ndaki (264-349) 273 hasta verisiyle yap\u0131lan IPD meta-analizinde, \u00f6len 32 hastan\u0131n sadece be\u015fi &gt;3ay tedavi alabilmi\u015f, di\u011ferleri tedavinin ilk \u00fc\u00e7 ay\u0131nda \u00f6lm\u00fc\u015ft\u00fcr; &gt;3 ay tedavi alabilen hastalar genellikle sa\u011f kalanlar oldu\u011fu i\u00e7in, tedavi s\u00fcresinin \u00f6l\u00fcm \u00fczerine etkisini tan\u0131mlayabilmek m\u00fcmk\u00fcn olmam\u0131\u015ft\u0131r. \u00d6l\u00fcmlerin hepsi ilk \u00fc\u00e7 ayda ger\u00e7ekle\u015fti\u011fi i\u00e7in \u00f6l\u00fcm sonlan\u0131m\u0131na g\u00f6re de\u011ferlendirildi\u011finde \u00e7\u0131kan fark yanl\u0131l\u0131k i\u00e7ermektedir.<\/p>\n<p class=\"p3\">\u00dc\u00e7 aydan fazla tedavi alan ve almayan hastalar aras\u0131nda \u00f6l\u00fcm d\u0131\u015f\u0131 istenmeyen sonlan\u0131mlar\u0131n g\u00f6r\u00fclme s\u0131kl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan bir fark bulunmam\u0131\u015ft\u0131r [16\/113 (%14.15)\u2019e kar\u015f\u0131l\u0131k 16\/132 (%12.12); <i>p<\/i>=0.949]. (Bkz. Ek Tablo 24, 25, 27-29, 37)<\/p>\n<p class=\"p3\"><strong>\u00d6nerinin Gerek\u00e7esi:<\/strong> Eldeki veriler <i>Brucella <\/i>spp.\u2019ye ba\u011fl\u0131 endokardit olgular\u0131nda tedavi s\u00fcresinin ne kadar olmas\u0131 gerekti\u011fi konusunda \u00f6neri yapabilmek i\u00e7in yeterli de\u011fildir. <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> <i>Brucella <\/i>spp.\u2019ye ba\u011fl\u0131 endokardit nedeniyle izlenen hastalarda uygun tedavi s\u00fcresinin belirlenebilmesi i\u00e7in, farkl\u0131 tedavi rejimlerini, \u00f6l\u00fcm ve relaps\u0131, yeniden hastane yat\u0131\u015f\u0131n\u0131, ila\u00e7 istenmeyen etkileri gibi sonlan\u0131mlar\u0131 kar\u015f\u0131la\u015ft\u0131ran, g\u00f6zlemsel ve randomize-kontroll\u00fc \u00e7al\u0131\u015fmalar yap\u0131lmas\u0131 gereklidir.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h4 class=\"p2\">17- <i>Brucella<\/i> spp. spondilodiskiti tedavisinde doksisiklin + streptomisin rejimi, doksisiklin + rifampisin rejimine \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp. spondilodiskiti olan hastalarda DOX-STREP rejimini DOX-RIF rejimiyle kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n meta-analizinde, var olan \u00e7al\u0131\u015fmalar\u0131n kan\u0131t d\u00fczeylerinin kalitesinin yetersiz oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella<\/i> spp. spondilodiskiti tedavisinde antimikrobiyal tedavi rejimi konusunda kan\u0131ta dayal\u0131 \u00f6neri yap\u0131labilmesi m\u00fcmk\u00fcn de\u011fildir; bu konuda bilgi bo\u015flu\u011fu vard\u0131r. Akut bruselloz tedavi rejimlerini kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n meta-analizinde STREP i\u00e7eren rejimin daha etkili bulunmu\u015f olmas\u0131 nedeniyle ve ek olarak rehberi haz\u0131rlayan uzmanlar\u0131n da uzla\u015f\u0131s\u0131yla, <i>Brucella<\/i> spp. spondilodiskiti tedavisinde de DOX-STREP rejimine \u00f6ncelik verilmesi \u00f6nerilmi\u015ftir (<i>Bilgi bo\u015flu\u011fu<\/i>).<\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> \u0130kisi randomize kontroll\u00fc, d\u00f6rd\u00fc g\u00f6zlemsel \u00e7al\u0131\u015fma olmak \u00fczere toplam alt\u0131 \u00e7al\u0131\u015fman\u0131n verileri incelendi (219, 351-355). \u00c7al\u0131\u015fma verileri relaps ve tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan ayr\u0131 ayr\u0131 analize dahil edilerek sonu\u00e7lar elde edildi. Be\u015f \u00e7al\u0131\u015fman\u0131n i\u00e7erdi\u011fi toplam 288 hastada tedavi rejimlerinin relaps geli\u015fimi \u00fczerine etkisi ve alt\u0131 \u00e7al\u0131\u015fman\u0131n i\u00e7erdi\u011fi toplam 382 hastada tedavi rejimlerinin tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 \u00fczerine etkisi de\u011ferlendiridi. DOX+STREP rejimi ile DOX+RIF rejimi aras\u0131nda relaps (OR=0.64, %95 GA=0.23-1.74) ve tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131\u00a0(OR=0.84, %95 GA=0.43-1.64) a\u00e7\u0131s\u0131ndan istatistiksel olarak fark saptanmad\u0131.<\/p>\n<p class=\"p3\">Ariza ve arkada\u015flar\u0131n\u0131n (219) tek merkezde ger\u00e7ekle\u015ftirdikleri randomize kontroll\u00fc, \u00e7ift k\u00f6r \u00e7al\u0131\u015fmada bruselloz tan\u0131s\u0131 alan 95 hasta DOX+STREP ve DOX+RIF tedavi kollar\u0131nda de\u011ferlendirilmi\u015ftir. Fokal tutulumlu osteoartik\u00fcler bruselloz olgular\u0131n\u0131n alt grupta de\u011ferlendirildi\u011fi bu \u00e7al\u0131\u015fmada sonlan\u0131m noktalar\u0131 tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 ve relaps olup ortalama takip s\u00fcresi 15 ayd\u0131r. DOX+STREP alan dokuz osteoartik\u00fcler bruselloz hastas\u0131n\u0131n birinde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, ikisinde relaps g\u00f6r\u00fcl\u00fcrken; DOX+RIF tedavisi alan dokuz osteoartik\u00fcler bruselloz hastas\u0131n\u0131n ikisinde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, ikisinde relaps izlenmi\u015ftir.<\/p>\n<p class=\"p3\">Bay\u0131nd\u0131r ve arkada\u015flar\u0131n\u0131n (351) yapm\u0131\u015f oldu\u011fu randomize kontroll\u00fc, a\u00e7\u0131k etiketli, tek merkezli \u00e7al\u0131\u015fmada, be\u015f tedavi rejimine (STREP-TET, STREP-DOX, STREP-DOX-RIF, DOX-RIF, OFX-RIF) randomize edilmi\u015f toplam 102 <i>Brucella<\/i> spp. spondilodiskiti olgusu, tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 ve relaps a\u00e7\u0131s\u0131ndan en az alt\u0131 ay izlenmi\u015ftir. STREP+DOX alan 21 hastan\u0131n d\u00f6rd\u00fcnde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015f ve relaps izlenmemi\u015f; DOX+RIF alan 20 hastan\u0131n \u00fc\u00e7\u00fcnde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, ikisinde ise relaps g\u00f6r\u00fclm\u00fc\u015ft\u00fcr.<\/p>\n<p class=\"p3\">Buzgan ve arkada\u015flar\u0131n\u0131n (352), 1028 bruselloz olgusunun klinik \u00f6zellikleri ve komplikasyonlar\u0131n\u0131 de\u011ferlendirdi\u011fi retrospektif g\u00f6zlemsel, tek merkezli \u00e7al\u0131\u015fmada, 141 osteoartik\u00fcler bruselloz olgusu farkl\u0131 tedavi rejimleri al\u0131rken relaps a\u00e7\u0131s\u0131ndan de\u011ferlendirilmi\u015ftir. Otuz be\u015f olgu DOX+RIF, 41 olgu DOX+STREP kullanm\u0131\u015f olup hastalar 12 ay takip edilmi\u015ftir. Bu tedavi rejimlerinde relaps oranlar\u0131 s\u0131ras\u0131yla %11.4 (n=4) ve %7.3 (n=3) olarak bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Colmenero ve arkada\u015flar\u0131n\u0131n (353), tek merkezde ger\u00e7ekle\u015ftirdikleri restrospektif g\u00f6zlemsel \u00e7al\u0131\u015fmada, doz ve s\u00fcrenin belirtilmedi\u011fi DOX+STREP ve DOX+RIF olan iki tedavi kolunda yer alan 87 brusella spondilodiskiti olan hasta tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, relaps, sekel ve mortalite a\u00e7\u0131s\u0131ndan de\u011ferlendirilmi\u015ftir. DOX+STREP tedavisi alan 71 hastan\u0131n 11\u2019inde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, ikisinde mortalite, be\u015finde sekel izlenirken, relaps g\u00f6r\u00fclmemi\u015ftir. DOX+RIF tedavisi alan 16 hastan\u0131n \u00fc\u00e7\u00fcnde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, birinde sekel izlenirken, relaps ve mortalite g\u00f6r\u00fclmemi\u015ftir.<\/p>\n<p class=\"p3\">Jia ve arkada\u015flar\u0131n\u0131n (354), 590 bruselloz hastas\u0131ndaki tedavi komplikasyonlar\u0131n\u0131 de\u011ferlendirdi\u011fi retrospekif g\u00f6zlemsel, tek merkezli \u00e7al\u0131\u015fmada osteoartik\u00fcler tutulumu olan hastalar farkl\u0131 tedavi rejimleri sonras\u0131 alt\u0131 ay boyunca relaps a\u00e7\u0131s\u0131ndan izlenmi\u015ftir. DOX+RIF alan 55 hastan\u0131n d\u00f6rd\u00fcnde, DOX+STREP alan 11 hastan\u0131n ikisinde relaps izlendi\u011fi bildirilmi\u015ftir.<\/p>\n<p class=\"p3\">Ulu-K\u0131l\u0131\u00e7 ve arkada\u015flar\u0131n\u0131n (355), komplike ve komplike olmayan spinal bruselloz tedavisini de\u011ferlendirdi\u011fi retrospektif g\u00f6zlemsel, \u00e7ok merkezli \u00e7al\u0131\u015fmada farkl\u0131 tedavi rejimi kullanan toplam 277 hasta tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan de\u011ferlendirilmi\u015ftir. DOX+STREP alan sekiz hastan\u0131n birinde, DOX+RIF alan 95 hastan\u0131n sekizinde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. (Bkz. Ek \u015eekil 32, 33 ve Ek Tablo 38, 39)<\/p>\n<p class=\"p3\"><strong>\u00d6nerinin Gerek\u00e7esi:<\/strong> \u00c7al\u0131\u015fmalarda relaps i\u00e7in takip s\u00fcresi 6-15 ay aras\u0131nda de\u011fi\u015fmektedir ve relaps tan\u0131mlar\u0131 net de\u011fildir. \u00dc\u00e7 \u00e7al\u0131\u015fmada genel bruselloz olgular\u0131n\u0131n alt grubunda osteoartik\u00fcler tutulumu olan hastalar bulunmaktad\u0131r ve analiz bu olgular\u0131n verileriyle yap\u0131lm\u0131\u015ft\u0131r (219,352,354). S\u00f6z konusu \u00e7al\u0131\u015fmalar brusella spondilodiskiti i\u00e7in tasarlanm\u0131\u015f \u00e7al\u0131\u015fmalar de\u011fildir. <i>Brucella<\/i> spp. spondilodiskiti olan hastalarda DOX+STREP rejimini DOX+RIF ile kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n meta-analizinde, var olan \u00e7al\u0131\u015fmalar\u0131n kan\u0131t d\u00fczeylerinin ve kalitesinin yetersiz oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella<\/i> spp. spondilodiskiti tedavisinde antimikrobiyal tedavi rejimi konusunda bilgi bo\u015flu\u011fu vard\u0131r, \u00f6neri yap\u0131labilmesi m\u00fcmk\u00fcn de\u011fildir.<span class=\"s9\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131: <\/strong>Standart dozda tedavi verilen ve benzer s\u00fcrelerde takip edilen brusella spondilodiskiti hastalar\u0131nda DOX+STREP ve DOX+RIF tedavisinin etkinli\u011fini g\u00f6sterecek randomize kontroll\u00fc \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n<h4 class=\"p2\">18- <i>Brucella <\/i>spp. spondilodiskiti tedavisinde 3\u2019l\u00fc antimikrobiyal kombinasyon rejimleri, 2\u2019li kombinasyon rejimlerinden \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp. spondilodiskiti olan hastalarda tedavi rejimlerini kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n meta-analizinde, 3\u2019l\u00fc antimikrobiyal kombinasyonlar\u0131n, 2\u2019li kombinasyonlardan daha ba\u015far\u0131l\u0131 oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella <\/i>spp. spondilodiskiti tedavisinde \u00fc\u00e7 antimikrobiyal i\u00e7eren kombinasyon tedavisi \u00f6nerilir <i>(\u00c7ok d\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, zay\u0131f \u00f6neri).<\/i><\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> \u00d6neriyle ilgili kan\u0131tlar, biri randomize kontroll\u00fc, d\u00f6rd\u00fc g\u00f6zlemsel \u00e7al\u0131\u015fma olmak \u00fczere toplam be\u015f \u00e7al\u0131\u015fman\u0131n verilerine dayanmaktad\u0131r (351-353, 355, 358). S\u00f6z konusu \u00e7al\u0131\u015fmalar\u0131n verileri tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan analize dahil edilerek sonu\u00e7lar elde edilmi\u015ftir; toplam 704 hastada, <i>Brucella <\/i>spp<i>.<\/i>\u2019ye etkili 3\u2019l\u00fc rejimle, 2\u2019li rejimin tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 \u00fczerine etkisi de\u011ferlendirilmi\u015ftir. <i>Brucella <\/i>spp.\u2019ye etkili 2\u2019li rejimle kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda 3\u2019l\u00fc rejim daha az tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 (OR=0.50, %95 GA=0.29-0.89) ile ili\u015fkilidir. Tedavide kullan\u0131lan ila\u00e7lar a\u00e7\u0131s\u0131ndan, DOX+STREP+RIF rejimiyle DOX+STREP kombinasyonunun kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131 biri randomize kontroll\u00fc, \u00fc\u00e7\u00fc g\u00f6zlemsel olmak \u00fczere toplam d\u00f6rt \u00e7al\u0131\u015fmadaki 344 hastan\u0131n verileri analiz edildi\u011finde, DOX+STREP+RIF rejiminin tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan DOX+STREP rejimine \u00fcst\u00fcnl\u00fc\u011f\u00fc g\u00f6sterilememi\u015ftir (OR=0.67, %95 GA=0.28-1.62). DOX+STREP+RIF rejimiyle DOX+RIF alan hastalar\u0131n yer ald\u0131\u011f\u0131 biri randomize kontroll\u00fc, ikisi g\u00f6zlemsel \u00e7al\u0131\u015fma sonu\u00e7lar\u0131n\u0131 i\u00e7eren toplam \u00fc\u00e7 \u00e7al\u0131\u015fmadaki 347 hastan\u0131n verileri analiz edildi\u011finde, DOX+STREP+RIF rejiminin tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan DOX+RIF rejimine \u00fcst\u00fcnl\u00fc\u011f\u00fc g\u00f6sterilememi\u015ftir (OR=0.55, %95 GA=0.78-1.15).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Bay\u0131nd\u0131r ve arkada\u015flar\u0131n\u0131n 17. soruda detaylar\u0131 verilmi\u015f olan \u00e7al\u0131\u015fmas\u0131nda (351), STREP+DOX+RIF ile 3\u2019l\u00fc kombinasyon tedavisi alan 22 hastada tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 ve relaps g\u00f6r\u00fclmemi\u015fken, 2\u2019li STREP+TET tedavi kombinasyonu alan 20 hastan\u0131n ikisinde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015f, relaps izlenmemi\u015f; 2\u2019li STREP+DOX tedavi kombinasyonu alan 21 hastan\u0131n d\u00f6rd\u00fcnde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015f, relaps izlenmemi\u015f; 2\u2019li DOX+RIF tedavi kombinasyonu alan 20 hastan\u0131n \u00fc\u00e7\u00fcnde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, ikisinde relaps g\u00f6r\u00fclm\u00fc\u015f; 2\u2019li OFX+RIF tedavi kombinasyonu alan 19 hastan\u0131n ise be\u015finde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131, be\u015finde relaps izlenmi\u015ftir.<\/p>\n<p class=\"p3\">Buzgan ve arkada\u015flar\u0131n\u0131n (352) 17. soruda detaylar\u0131 verilmi\u015f olan \u00e7al\u0131\u015fmas\u0131nda, 53 olgu DOX+STREP+RIF i\u00e7eren 3\u2019l\u00fc tedavi rejimiyle izlenmi\u015f, bu gruptaki hastalarda 12. ayda relaps oran\u0131n\u0131n % 5.7 (n=3) \u015feklinde g\u00f6zlendi\u011fi ve di\u011fer tedavi rejimlerine g\u00f6re daha d\u00fc\u015f\u00fck oldu\u011fu bildirilmi\u015ftir.<span class=\"Apple-converted-space\">\u00a0 <\/span>Bu \u00e7al\u0131\u015fmada 35 olgu DOX+RIF, 41 olgu DOX+STREP, 12 olgu ise CIP+DOX \u015feklinde 2\u2019li tedavi rejimi kullanm\u0131\u015f olup 2\u2019li tedavi alan gruplarda relaps oranlar\u0131 s\u0131ras\u0131yla %11.4 (n=4), %7.3 (n=3) ve %16.7 (n=2) olarak bulunmu\u015ftur.<\/p>\n<p class=\"p3\">Jia ve arkada\u015flar\u0131n\u0131n (353) 17. soruda detaylar\u0131 verilmi\u015f olan \u00e7al\u0131\u015fmas\u0131nda, DOX+RIF+levofloksasin (LEV) ile 3\u2019l\u00fc tedavi rejimi alan 39 hastan\u0131n ikisinde relaps izlenirken, 2\u2019li tedavi rejimlerinden DOX+RIF alan 55 hastan\u0131n d\u00f6rd\u00fcnde, DOX+STREP alan 11 hastan\u0131n ikisinde, DOX+moksifloksasin (MOX) alan 17 hastan\u0131n \u00fc\u00e7\u00fcnde ve RIF+LEV alan 15 hastan\u0131n \u00fc\u00e7\u00fcnde relaps izlenmi\u015ftir.<\/p>\n<p class=\"p3\">Ulu-K\u0131l\u0131\u00e7 ve arkada\u015flar\u0131n\u0131n (355) 17. soruda detaylar\u0131 verilmi\u015f olan \u00e7al\u0131\u015fmas\u0131nda, 3\u2019l\u00fc tedavi rejimlerinden DOX+RIF+STREP kullanan 141 hastan\u0131n 11\u2019inde, DOX+RIF+GEN alan 22 hastan\u0131n hi\u00e7birinde, DOX+RIF+CIP kullanan 11 hastan\u0131n birinde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fcl\u00fcrken; 2\u2019li tedavi rejimlerinden DOX+STREP alan sekiz hastan\u0131n birinde ve DOX+RIF alan 95 hastan\u0131n sekizinde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr.<\/p>\n<p class=\"p3\">Mermut ve arkada\u015flar\u0131n\u0131n (357) retrospektif g\u00f6zlemsel \u00e7al\u0131\u015fmas\u0131nda, osteoartik\u00fcler tutulumu olan 70 hastada DOX+STREP+RIF tedavisi alanlarla DOX+STREP tedavisi alanlar relaps a\u00e7\u0131s\u0131ndan de\u011ferlendirilmi\u015ftir; DOX+STREP+RIF tedavisi alan 42 hastada relaps oran\u0131 %7 (n=3), DOX+STREP tedavisi alan hastalarda relaps oran\u0131 %11 (n=7) olarak bulunmu\u015ftur. (Bkz. Ek \u015eekil 34-36 ve Ek Tablo 40, 41)<\/p>\n<p class=\"p3\"><strong>\u00d6nerinin Gerek\u00e7esi:<\/strong> <i>Brucella<\/i> spp. spondilodiskiti olan hastalarda tedavi rejimlerini kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n meta-analizinde, 3\u2019l\u00fc antimikrobiyal kombinasyonlar\u0131n, 2\u2019li kombinasyonlardan daha ba\u015far\u0131l\u0131 oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella <\/i>spp. spondilodiskiti tedavisinde \u00fc\u00e7 antimikrobiyal i\u00e7eren kombinasyon tedavisi \u00f6nerilir.<\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> Randomize kontroll\u00fc \u00e7al\u0131\u015fmalar\u0131n olmay\u0131\u015f\u0131 ve kullan\u0131lan tedavi rejimlerinin farkl\u0131 ajanlar i\u00e7erip standart olmay\u0131\u015f\u0131 nedeniyle kan\u0131ta dayal\u0131 g\u00fc\u00e7l\u00fc \u00f6neri yapmak olduk\u00e7a g\u00fc\u00e7t\u00fcr. Bu alanda, DOX+STREP+RIF rejimiyle DOX+STREP veya DOX+RIF rejimini kar\u015f\u0131la\u015ft\u0131racak, daha fazla say\u0131da hasta i\u00e7eren randomize kontroll\u00fc \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n<h4 class=\"p2\">19- <i>Brucella<\/i> spp. spondilodiskiti tedavisinde kinolon i\u00e7eren tedavi rejimleri i\u00e7ermeyen rejimlere \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp. spondilodiskiti olan hastalarda kinolon i\u00e7eren antimikrobiyal kombinasyonlarla, i\u00e7ermeyen kombinasyonlar\u0131 kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n meta-analizinde, var olan \u00e7al\u0131\u015fmalar\u0131n kan\u0131t d\u00fczeylerinin ve kalitesinin yetersiz oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella<\/i> spp. spondilodiskiti tedavisinde kinolon i\u00e7eren kombinasyonlar\u0131n kullan\u0131m\u0131 konusunda kan\u0131ta dayal\u0131 \u00f6neri yap\u0131labilmesi m\u00fcmk\u00fcn de\u011fildir, bu konuda bilgi bo\u015flu\u011fu vard\u0131r. Rehber grubunda yer alan uzmanlar taraf\u0131ndan, <i>Brucella<\/i> spp. spondilodiskiti olgular\u0131n\u0131n kombinasyon tedavisinde kinolonlar\u0131n, bu<span class=\"Apple-converted-space\">\u00a0 <\/span>grup antimikrobiklerle ilgili artan g\u00fcvenlik endi\u015feleri nedeniyle,<span class=\"Apple-converted-space\">\u00a0 <\/span>ilk se\u00e7enek<span class=\"Apple-converted-space\">\u00a0 <\/span>olarak yer almamas\u0131, ilk se\u00e7enek ila\u00e7lar\u0131n (DOX, RIF, GEN, STREP) yan etki, ila\u00e7 etkile\u015fimi gibi herhangi bir nedenle kullan\u0131lamad\u0131\u011f\u0131 durumlarda d\u00fc\u015f\u00fcn\u00fclmesi \u00f6nerilir (<i>Bilgi bo\u015flu\u011fu<\/i>).<\/p>\n<p class=\"p3\"><span class=\"s2\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> Biri randomize kontroll\u00fc, d\u00f6rd\u00fc g\u00f6zlemsel \u00e7al\u0131\u015fma olmak \u00fczere toplam be\u015f \u00e7al\u0131\u015fman\u0131n verileri incelenmi\u015ftir (351,352,354, 355,359). Veriler tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan analiz edilmi\u015f ve toplam 665 hastada<i> <\/i>kinolon i\u00e7eren rejimle kinolon i\u00e7ermeyen rejimlerin tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 \u00fczerine etkisi de\u011ferlendirilmi\u015ftir. Kinolon i\u00e7eren rejim kinolon i\u00e7ermeyen rejime g\u00f6re daha fazla tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 (OR=2.30, %95 GA=1.26-4.19) ile ili\u015fkilidir. Ayr\u0131ca 2\u2019li tedavi rejimine (DOX-STREP veya DOX-RIF) kinolon eklenmesi ve eklenmemesi aras\u0131nda tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan fark olup olmad\u0131\u011f\u0131n\u0131 de\u011ferlendirebilmek i\u00e7in 297 hasta i\u00e7eren toplam \u00fc\u00e7 g\u00f6zlemsel \u00e7al\u0131\u015fman\u0131n verileri analiz edilmi\u015ftir. Tedavi ba\u015far\u0131s\u0131 i\u00e7in 2\u2019li tedaviye kinolon eklenmesinin (OR=0.96, %95 GA=0.34-2.70) \u00fcst\u00fcnl\u00fc\u011f\u00fc g\u00f6sterilememi\u015ftir. Ancak bahsedilen \u00e7al\u0131\u015fmalarda tedavi rejimleri olduk\u00e7a heterojen olup kinolon grubundan farkl\u0131 ila\u00e7lar bulunmaktad\u0131r.<span class=\"Apple-converted-space\">\u00a0<\/span><\/span><\/p>\n<p class=\"p3\">Alp ve arkada\u015flar\u0131n\u0131n (357) prospektif, randomize olmayan \u00e7al\u0131\u015fmas\u0131nda, spinal tutulumla seyreden brusellozda DOX+STREP ve CIP+RIF tedavileri kar\u015f\u0131la\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. S\u0131ras\u0131yla 15 ve 16 hastan\u0131n de\u011ferlendirildi\u011fi \u00e7al\u0131\u015fmada her iki tedavi rejiminde de relaps izlenmemi\u015ftir. DOX+STREP alanlar\u0131n sekizinde hafif derecede, birinde orta derecede sekel g\u00f6r\u00fclm\u00fc\u015f olup CIP+RIF alanlar\u0131n ise dokuzunda hafif derecede, ikisinde orta derecede sekel g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Burada g\u00f6r\u00fclen sekeller tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 olarak de\u011ferlendirilmi\u015ftir.<\/p>\n<p class=\"p3\">Bay\u0131nd\u0131r ve arkada\u015flar\u0131n\u0131n (351) 17. soruda detaylar\u0131 verilmi\u015f olan \u00e7al\u0131\u015fmas\u0131nda, kinolon i\u00e7eren rejimlerden OFX+RIF alan 19 hastan\u0131n 10 (%52)\u2019unda tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 (5 hastada) veya relaps (5 hastada) izlenmi\u015fken, kinolon i\u00e7ermeyen di\u011fer rejimlerde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 ve relaps oranlar\u0131n\u0131n %0-25 aras\u0131nda de\u011fi\u015fti\u011fi bildirilmi\u015ftir. <span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Buzgan ve arkada\u015flar\u0131n\u0131n (352) 17. soruda detaylar\u0131 verilmi\u015f olan \u00e7al\u0131\u015fmas\u0131nda, 12 olguda CIP+DOX, 35 olguda DOX+RIF, 41 olguda DOX+STREP, 53 olguda ise DOX+STREP+RIF tedavi rejimleri uygulanm\u0131\u015f ve 12 ay i\u00e7inde relaps oran\u0131 di\u011fer t\u00fcm rejimlerdeki oranlardan fazla olacak \u015fekilde %16.7 bulunmu\u015ftur.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\">Jia ve arkada\u015flar\u0131n\u0131n (354) 17. soruda detaylar\u0131 verilmi\u015f olan \u00e7al\u0131\u015fmas\u0131nda, kinolon i\u00e7eren rejimlerden DOX+RIF+LEV alan 39 hastan\u0131n ikisinde, DOX+MOX alan 17 hastan\u0131n \u00fc\u00e7\u00fcnde, RIF+LEV alan 15 hastan\u0131n \u00fc\u00e7\u00fcnde relaps izlenmi\u015fken; kinolon i\u00e7ermeyen rejimlerden DOX+RIF alan 55 hastan\u0131n d\u00f6rd\u00fcnde, DOX+STR alan 11 hastan\u0131n ikisinde relaps izlenmi\u015ftir.<\/p>\n<p class=\"p3\">Ulu-K\u0131l\u0131\u00e7 ve arkada\u015flar\u0131n\u0131n (355) 17. soruda detaylar\u0131 verilmi\u015f olan \u00e7al\u0131\u015fmas\u0131nda, kinolon i\u00e7eren rejimlerden DOX+RIF+CIP alan 11 hastan\u0131n birinde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fcl\u00fcrken, kinolon i\u00e7ermeyen rejimlerden DOX+STREP alan sekiz hastan\u0131n birinde, DOX+RIF+STREP alan 141 hastan\u0131n 11\u2019inde, DOX+RIF alan 95 hastan\u0131n sekizinde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Ayn\u0131 \u00e7al\u0131\u015fmada, DOX+RIF+CN alan 22 hastan\u0131n hi\u00e7birinde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fclmemi\u015ftir. (Bkz. Ek \u015eekil 37, 38 ve Ek Tablo 42, 43).<\/p>\n<p class=\"p3\"><strong>\u00d6nerinin Gerek\u00e7esi:<\/strong> Kinolon grubu antibiyotiklerin standart ila\u00e7lar olan DOX, STREP ve RIF yerine kullan\u0131lmas\u0131 uygun de\u011fildir. Ayr\u0131ca standart tedavi rejimine eklendi\u011finde de benzer sonu\u00e7lar elde edilmektedir. Kinolonlar istenmeyen etkiler dolay\u0131s\u0131yla standart ila\u00e7lar\u0131n kullan\u0131lamad\u0131\u011f\u0131 durumlarda alternatif tedavide d\u00fc\u015f\u00fcn\u00fclmelidir.<b> <\/b><i>Brucella<\/i> spp. spondilodiskiti olan hastalarda kinolon i\u00e7eren antimikrobiyal kombinasyonlarla, i\u00e7ermeyen\u00a0kombinasyonlar\u0131 kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n kan\u0131t d\u00fczeylerinin ve kalitesinin yetersiz oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella<\/i> spp. spondilodiskiti tedavisinde kinolon i\u00e7eren kombinasyonlar\u0131n kullan\u0131m\u0131 konusunda bilgi bo\u015flu\u011fu vard\u0131r, \u00f6neri yap\u0131labilmesi m\u00fcmk\u00fcn de\u011fildir.<span class=\"s10\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> Kinolon i\u00e7eren rejimlerle i\u00e7ermeyen rejimlerin kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131 randomize kontroll\u00fc \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n<h4 class=\"p2\">20- <i>Brucella<\/i> spp. spondilodiskiti tedavisinde \u00fc\u00e7 aydan uzun s\u00fcreli tedavi \u00fc\u00e7 aydan k\u0131sa s\u00fcreli tedavilere \u00fcst\u00fcn m\u00fcd\u00fcr?<\/h4>\n<p class=\"p3\"><strong>\u00d6neri:<\/strong> <i>Brucella<\/i> spp. spondilodiskiti olan hastalarda \u00fc\u00e7 aydan uzun s\u00fcren antimikrobiyal tedavi rejimlerini, \u00fc\u00e7 aydan k\u0131sa tedavilerle kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n meta-analizinde, var olan \u00e7al\u0131\u015fmalar\u0131n kan\u0131t d\u00fczeylerinin ve kalitesinin yetersiz oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella<\/i> spp. spondilodiskitinde ideal tedavi s\u00fcresi konusunda kan\u0131ta dayal\u0131 \u00f6neri yap\u0131labilmesi m\u00fcmk\u00fcn de\u011fildir, bu konuda bilgi bo\u015flu\u011fu vard\u0131r. Rehber grubunda yer alan uzmanlar taraf\u0131ndan, <i>Brucella<\/i> spp. spondilodiskiti tedavisinin en az \u00fc\u00e7 ay uygulanmas\u0131, tedavi sonunda klinik ve radyolojik olarak hasta baz\u0131nda yap\u0131lacak de\u011ferlendirmeye g\u00f6re s\u00fcrenin<span class=\"Apple-converted-space\">\u00a0 <\/span>uzat\u0131lmas\u0131 \u00f6nerilir (<i>Bilgi bo\u015flu\u011fu<\/i>).<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p class=\"p3\"><strong>Kan\u0131tlar\u0131n \u00d6zeti:<\/strong> \u00dc\u00e7 g\u00f6zlemsel \u00e7al\u0131\u015fman\u0131n verileri incelendi (358-360). \u00c7al\u0131\u015fma verileri tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 (relaps ve sekel) a\u00e7\u0131s\u0131ndan analize dahil edilerek sonu\u00e7lar elde edildi. \u00dc\u00e7 \u00e7al\u0131\u015fman\u0131n i\u00e7erdi\u011fi toplam 157 hastada<i> <\/i>\u00fc\u00e7 aydan uzun s\u00fcreli herhangi bir tedavi rejimiyle \u00fc\u00e7 ay ve daha az s\u00fcreli herhangi bir tedavi rejiminin tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 \u00fczerine etkisi de\u011ferlendirildi. \u00dc\u00e7 aydan uzun s\u00fcreli tedavi verilmesinin, tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 a\u00e7\u0131s\u0131ndan, \u00fc\u00e7 ay ve daha az tedavi verilmesine \u00fcst\u00fcnl\u00fc\u011f\u00fc g\u00f6sterilemedi (OR=0.63, %95 GA=0.25-1.57). Analize farkl\u0131 iki s\u00fcreyi kar\u015f\u0131la\u015ft\u0131rmad\u0131\u011f\u0131 i\u00e7in dahil edilemeyen ancak uzun s\u00fcreli tedavinin (en az alt\u0131 ay) ba\u015far\u0131s\u0131n\u0131 vurgulayan Ioannou ve arkada\u015flar\u0131n\u0131n (361) \u00e7al\u0131\u015fmas\u0131nda da vurguland\u0131\u011f\u0131 gibi tedavi s\u00fcresine klinik ve radyolojik bulgulara g\u00f6re hasta baz\u0131nda karar verilebilir.<\/p>\n<p class=\"p3\">El Miedany ve arkada\u015flar\u0131n\u0131n (358), prospektif g\u00f6zlemsel, \u00e7ok merkezli \u00e7al\u0131\u015fmas\u0131nda yap\u0131lan analizlerden birinde osteoartik\u00fcler brusellozda farkl\u0131 s\u00fcrelerde tedavi verilen hastalarda relaps oranlar\u0131 de\u011ferlendirilmi\u015ftir. Bu \u00e7al\u0131\u015fmada \u00fc\u00e7 aydan az tedavi alan yedi hastan\u0131n 4 (%57.1)\u2019\u00fcnde relaps g\u00f6r\u00fcl\u00fcrken, \u00fc\u00e7 aydan uzun s\u00fcre tedavi alan 90 hastan\u0131n 17 (%18.8)\u2019sinde relaps g\u00f6r\u00fclm\u00fc\u015ft\u00fcr.<\/p>\n<p class=\"p3\">Solera ve arkada\u015flar\u0131n\u0131n (359) prospektif g\u00f6zlemsel \u00e7al\u0131\u015fmas\u0131nda, brusella spondilodiskiti olan 35 hasta, 1-6 y\u0131l aras\u0131nda de\u011fi\u015fen s\u00fcrelerde izlenmi\u015f olup sekel geli\u015fen hastalar\u0131n sonu\u00e7lar\u0131 tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 olarak de\u011ferlendirildi. \u00dc\u00e7 aydan az tedavi alan 21 hastan\u0131n 15 (%71.4)\u2019inde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fcl\u00fcrken, \u00fc\u00e7 aydan fazla tedavi alan 14 hastan\u0131n 9 (%64.2)\u2019unda tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fcld\u00fc.<\/p>\n<p class=\"p3\">Y\u0131lmaz ve arkada\u015flar\u0131n\u0131n (360) retrospektif g\u00f6zlemsel \u00e7al\u0131\u015fmas\u0131nda, brusella spondilodiskiti olan 25 hasta 1 ay-10 y\u0131l aras\u0131nda de\u011fi\u015fen s\u00fcrelerde izlenmi\u015f olup sekel geli\u015fen hastalar\u0131n sonu\u00e7lar\u0131 tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 olarak de\u011ferlendirildi. \u00dc\u00e7 aydan az tedavi alan be\u015f hastan\u0131n 1 (%20)\u2019inde tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fcl\u00fcrken, \u00fc\u00e7 aydan fazla tedavi alan 20 hastan\u0131n 9 (%45)\u2019unda tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131 g\u00f6r\u00fcld\u00fc. (Bkz. Ek \u015eekil 39 ve Ek Tablo 44, 45)<\/p>\n<p class=\"p3\"><strong>\u00d6nerinin Gerek\u00e7esi:<\/strong> \u00c7al\u0131\u015fmalar analiz edilirken, \u00e7e\u015fitli tedavi rejimleri uygulanan hastalar tedavi s\u00fcresi \u00fc\u00e7 ay ve daha k\u0131sa s\u00fcreli olanlar ve \u00fc\u00e7 aydan uzun olanlar \u015feklinde iki gruba ayr\u0131lm\u0131\u015f ve tedavi sonras\u0131nda sekel g\u00f6r\u00fcl\u00fcp g\u00f6r\u00fclmemesine g\u00f6re tedavi ba\u015far\u0131s\u0131 de\u011ferlendirilmi\u015ftir. Tedavi rejimleri benzer de\u011fildir. Ayr\u0131ca <i>Brucella<\/i> spp. spondilodiskiti olan hastalarda \u00fc\u00e7 aydan uzun s\u00fcren antimikrobiyal tedavi rejimlerini, \u00fc\u00e7 aydan k\u0131sa s\u00fcren tedavilerle kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar\u0131n kan\u0131t d\u00fczeylerinin ve kalitesinin yetersiz oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <i>Brucella<\/i> spp. spondilodiskiti tedavisinin s\u00fcresinin ne kadar olmas\u0131 gerekti\u011fi konusunda bilgi bo\u015flu\u011fu vard\u0131r, \u00f6neri yap\u0131labilmesi m\u00fcmk\u00fcn de\u011fildir.<\/p>\n<p class=\"p3\"><strong>Bilgi A\u00e7\u0131\u011f\u0131:<\/strong> Brusella spondilodiskiti tedavisinde ayn\u0131 rejimi farkl\u0131 s\u00fcrelerde alan hasta verilerinin kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131 randomize kontroll\u00fc \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n<h4><button class=\"button button1\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2023\/07\/KLM-4576-Rehber_Ekleri.V2.pdf\">Ek Dok\u00fcmanlar\u0131 g\u00f6r\u00fcnt\u00fclemek i\u00e7in t\u0131klay\u0131n\u0131z. <\/a><\/button><\/h4>\n","protected":false},"excerpt":{"rendered":"<p>Bu makaleye ili\u015fkin\u00a0bir d\u00fczeltme 14 \u015eubat 2026\u2019da yay\u0131nland\u0131: https:\/\/doi.org\/10.36519\/kd.2026.5533 \u00d6NER\u0130LER\u0130N \u00d6ZET\u0130 1- Brusellozdan ku\u015fkulan\u0131lan hastalarda Rose Bengal testinin tan\u0131daki yeri nedir? \u00d6neri: Rose Bengal (RB) testinin bruselloz tan\u0131s\u0131nda duyarl\u0131l\u0131\u011f\u0131 y\u00fcksektir. Temas \u00f6yk\u00fcs\u00fc ve uyumlu semptomlar\u0131 olan hastalarda h\u0131zl\u0131 tan\u0131 testi olarak kullan\u0131lmas\u0131 \u00f6nerilir (D\u00fc\u015f\u00fck kan\u0131t d\u00fczeyi, g\u00fc\u00e7l\u00fc \u00f6neri). Yap\u0131lan meta-analizlerinde testin \u00f6zg\u00fcll\u00fc\u011f\u00fc de y\u00fcksek bulunmu\u015ftur, [&hellip;]<\/p>\n","protected":false},"author":4,"featured_media":27154,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[5730],"tags":[5728,5729,3716,3717,3456],"class_list":["post-26924","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-rehber","tag-brucella-2","tag-brucellosis-2","tag-tani","tag-tedavi","tag-the-evaluation-of-epidemiologic"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/26924","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/comments?post=26924"}],"version-history":[{"count":3,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/26924\/revisions"}],"predecessor-version":[{"id":31514,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/26924\/revisions\/31514"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/media\/27154"}],"wp:attachment":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/media?parent=26924"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/categories?post=26924"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/tags?post=26924"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}