{"id":23791,"date":"2021-12-27T12:15:52","date_gmt":"2021-12-27T09:15:52","guid":{"rendered":"https:\/\/www.klimikdergisi.org\/?p=23791"},"modified":"2022-02-10T10:02:07","modified_gmt":"2022-02-10T07:02:07","slug":"kolistin-duyarlilik-testi-yontemleri","status":"publish","type":"post","link":"https:\/\/www.klimikdergisi.org\/tr\/2021\/12\/27\/kolistin-duyarlilik-testi-yontemleri\/","title":{"rendered":"Karbapenem Diren\u00e7li Gram-negatif Bakterilerde Kolistin Duyarl\u0131l\u0131\u011f\u0131n\u0131n Saptanmas\u0131nda MIC COL, Sensititre\u2122 ve Kolistin Agar Tarama Pla\u011f\u0131 Y\u00f6ntemlerinin S\u0131v\u0131 Mikrodil\u00fcsyon Referans Y\u00f6ntemiyle Kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131"},"content":{"rendered":"<h2 class=\"p1\">G\u0130R\u0130\u015e<\/h2>\n<p class=\"p2\">Kolistin, Gram-negatif bakterilere kar\u015f\u0131 geni\u015f spektrumlu aktiviteye sahip polipeptid bir antibiyotiktir. Nefrotoksik ve n\u00f6rotoksik yan etkileri nedeniyle ge\u00e7mi\u015fte kullan\u0131m\u0131 s\u0131n\u0131rland\u0131r\u0131lm\u0131\u015ft\u0131r. Son y\u0131llarda, \u00e7oklu ve yayg\u0131n ila\u00e7 direnci g\u00f6steren Gram-negatiflerin prevalans\u0131n\u0131n artmas\u0131 nedeniyle bu bakteriler ile geli\u015fen infeksiyonlarda son se\u00e7enek antibiyotik olarak kolistin kullan\u0131m\u0131 artm\u0131\u015ft\u0131r (1). Fakat kullan\u0131m\u0131n\u0131n artmas\u0131na ba\u011fl\u0131 olarak bakterilerde kolistin direncinde art\u0131\u015f meydana gelmi\u015ftir. Yap\u0131lan \u00e7al\u0131\u015fmalarda \u00e7oklu ila\u00e7 direncine sahip <i>Klebsiella pneumoniae<\/i>, <i>Acinetobacter baumannii-calcoaceticus<\/i> kompleksi ve<span class=\"Apple-converted-space\">\u00a0 <\/span><i>Pseudomonas aeruginosa<\/i> izolatlar\u0131nda %13-43 aras\u0131nda kolistin direnci bildirilmi\u015ftir (2). Karbapenem diren\u00e7li bakteriler i\u00e7in yeni antibiyotikler kullan\u0131m onay\u0131 alsa da maliyetlerinin y\u00fcksek olmas\u0131 kullan\u0131mlar\u0131n\u0131 s\u0131n\u0131rland\u0131rmakta ve kolistin kullan\u0131m\u0131na ihtiya\u00e7 duyulmaktad\u0131r (3). Kolistin kullan\u0131m\u0131na duyulan ihtiya\u00e7 artt\u0131k\u00e7a kolistin duyarl\u0131l\u0131k testleri \u00f6nem kazanm\u0131\u015ft\u0131r. Ayr\u0131ca, \u00e7oklu ila\u00e7 diren\u00e7li Gram-negatif bakteriyel infeksiyonlarda <i>in vitro<\/i> kolistin diren\u00e7 testlerinin sonu\u00e7lar\u0131 uygun antibiyoterapi i\u00e7in \u00e7ok \u00f6nemlidir (2).<\/p>\n<p class=\"p2\">Avrupa Antimikrobiyal Duyarl\u0131l\u0131k Testi Komitesi (EUCAST- European Committee on Antimicrobial Susceptibility Testing) ve Klinik ve Laboratuvar Standardlar\u0131 Enstit\u00fcs\u00fc (CLSI &#8211; Clinical and Laboratory Standards Institute) kolistin duyarl\u0131l\u0131k testi i\u00e7in ISO 20776-1:2019 s\u0131v\u0131 mikrodil\u00fcsyon (SMD) referans y\u00f6nteminin kullan\u0131lmas\u0131n\u0131 \u00f6nermektedir (4, 5). Fakat s\u00f6z konusu y\u00f6ntemin rutin laboratuvar prati\u011finde uygulanmas\u0131, yo\u011fun emek gerektirmesi ve uzun s\u00fcrmesi nedeniyle zordur (2). CLSI\u2019nin yapt\u0131\u011f\u0131 bir \u00e7al\u0131\u015fmada, <i>Enterobacterales, P. aeruginosa<\/i> ve <i>A. baumannii<\/i>\u2019de, kolistin s\u0131v\u0131 disk el\u00fcsyon y\u00f6ntemi (KSDE) ve kolistin agar test (KAT) y\u00f6ntemi de\u011ferlendirilmi\u015f olup SMD ile uyumlar\u0131 y\u00fcksek, hata oranlar\u0131 d\u00fc\u015f\u00fck bulunmu\u015ftur (6). Bu bulgular do\u011frultusunda g\u00fcncel CLSI Rehberi, kolistin duyarl\u0131l\u0131\u011f\u0131n\u0131n saptanmas\u0131nda SMD y\u00f6ntemine ek olarak KSDE ve KAT y\u00f6ntemlerinin kabul edilebilir oldu\u011funu belirtmektedir (5). Laboratuvarlarda, antibiyotik duyarl\u0131l\u0131k testleri i\u00e7in s\u0131kl\u0131kla kullan\u0131lan VITEK\u00ae 2 (bioM\u00e9rieux, Marcy l\u2019Etoile, Fransa), MicroScan (Siemens AG FWB, Almanya) ya da BD Phoenix (Becton Dickinson, Sparks, MD, ABD) gibi otomatize sistemlerin sonu\u00e7lar\u0131 \u201c\u00e7ok b\u00fcy\u00fck hata\u201d (\u00c7BH) oranlar\u0131 nedeniyle g\u00fcvenilir bulunmamaktad\u0131r (7-9). Disk dif\u00fczyon ve gradyan testler, kolistin molek\u00fcllerinin agara dif\u00fczyonunun zay\u0131f olmas\u0131na ba\u011fl\u0131 olarak y\u00fcksek oranda yanl\u0131\u015f duyarl\u0131 sonu\u00e7lar al\u0131nmas\u0131na neden olmaktad\u0131r. Bu nedenle kullan\u0131lmas\u0131 \u00f6nerilmemektedir (2, 8). SMD y\u00f6ntemini temel alan, kullan\u0131m\u0131 kolay \u00e7e\u015fitli ticari paneller geli\u015ftirilmi\u015ftir. Yap\u0131lan \u00e7al\u0131\u015fmalarda bu panellerin SMD y\u00f6ntemi ile uyumu genellikle y\u00fcksek bulunmaktad\u0131r (9-12). Son y\u0131llarda, Nordmann ve arkada\u015flar\u0131 (13) taraf\u0131ndan Gram-negatif bakteri kolonilerinden ve klinik \u00f6rneklerden intrinsik ya da kazan\u0131lm\u0131\u015f kolistin direncini saptamaya y\u00f6nelik SuperPolymyxin\u2122 agar tarama pla\u011f\u0131 geli\u015ftirilmi\u015f olup duyarl\u0131l\u0131\u011f\u0131 %72.7-100, \u00f6zg\u00fcll\u00fc\u011f\u00fc %88.9-100 aras\u0131nda tespit edilmi\u015ftir (13).<\/p>\n<p class=\"p2\">\u00c7al\u0131\u015fmam\u0131zda, bir \u00fcniversite hastanesinde \u00e7e\u015fitli klinik \u00f6rneklerde saptanan karbapenem diren\u00e7li Gram-negatif basillerde, kolistin direncinin tespit edilmesinde; Sensititre\u2122 (Thermo Fisher Scientific, Cleveland, ABD) paneli, MIC COL (Diagnostics, Galanta, Slovakya) testi ve kolistin agar tarama pla\u011f\u0131n\u0131n performanslar\u0131n\u0131n SMD y\u00f6ntemi ile kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131; y\u00f6ntemlerin rutin kullan\u0131m a\u00e7\u0131s\u0131ndan uygunluklar\u0131n\u0131n yan\u0131 s\u0131ra avantaj ve dezavantajlar\u0131n\u0131n belirlenmesi ama\u00e7lanm\u0131\u015ft\u0131r.<\/p>\n<h2 class=\"p1\">GERE\u00c7 VE Y\u00d6NTEMLER<\/h2>\n<h3 class=\"p3\">Bakteri \u0130zolatlar\u0131<\/h3>\n<div id=\"attachment_24044\" style=\"width: 2193px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo1.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-24044\" class=\"size-full wp-image-24044\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo1.png\" alt=\"\" width=\"2183\" height=\"530\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo1.png 2183w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo1-390x95.png 390w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo1-810x197.png 810w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo1-768x186.png 768w\" sizes=\"auto, (max-width: 2183px) 100vw, 2183px\" \/><\/a><p id=\"caption-attachment-24044\" class=\"wp-caption-text\"><strong>Tablo 1.<\/strong> Bakterilerin \u0130zole Edildi\u011fi \u00d6rnek T\u00fcrlerinin Da\u011f\u0131l\u0131m\u0131<\/p><\/div>\n<p class=\"p4\">\u00c7al\u0131\u015fmaya, 1 Ocak 2020 ve 31 Ekim 2020 tarihleri aras\u0131nda hastanemizin Klinik Mikrobiyoloji Laboratuvar\u0131\u2019na gelen \u00e7e\u015fitli klinik \u00f6rneklerden izole edilen karbapenem diren\u00e7li 218 Gram-negatif basil<i> <\/i>[<i>K. pneumoniae <\/i>(n=91), <i>Klebsiella aerogenes <\/i>(n=1), <i>Klebsiella oxytoca <\/i>(n=1), <i>A. baumannii-calcoaceticus <\/i>kompleksi (n=83), <i>P. aeruginosa <\/i>(n=41), <i>Pseudomonas putida <\/i>(n=1)] dahil edilmi\u015ftir. Her hastadan yaln\u0131zca bir izolat \u00e7al\u0131\u015fmaya al\u0131nm\u0131\u015ft\u0131r. \u00c7al\u0131\u015fmaya dahil edilen bakterilerin izole edildikleri \u00f6rnek t\u00fcr\u00fcne g\u00f6re da\u011f\u0131l\u0131m\u0131 Tablo 1\u2019de g\u00f6sterilmi\u015ftir.<\/p>\n<p class=\"p4\">\u00c7al\u0131\u015fmaya dahil edilen bakteriler; Gram boyama, oksidaz testi, katalaz testi gibi konvansiyonel y\u00f6ntemler ve matriksle desteklenmi\u015f lazer dezorpsiyon iyonizasyon u\u00e7u\u015f zaman\u0131 k\u00fctle spektrometrisi (MALDI-TOF-MS) sistemiyle (Bruker, Almanya) tan\u0131mlanm\u0131\u015ft\u0131r. Karbapenem direnci; <i>Klebsiella<\/i> spp. ve <i>Pseudomonas<\/i> spp. izolatlar\u0131nda, BD Phoenix M50 (Becton Dickinson, Sparks, MD, ABD) otomatize sistemi ve Etest\u00ae (bioM\u00e9rieux, Marcy l\u2019Etoile, Fransa )<span class=\"s1\"> y\u00f6ntemi <\/span>ile belirlenirken<span class=\"Apple-converted-space\">\u00a0 <\/span><i>A. baumannii-calcoaceticus <\/i>kompleksi<i> <\/i>izolatlar\u0131nda EUCAST disk dif\u00fczyon y\u00f6ntemi kullan\u0131lm\u0131\u015ft\u0131r.<\/p>\n<h3 class=\"p3\"><i>In Vitro<\/i> Kolistin Duyarl\u0131l\u0131k Testleri<\/h3>\n<p class=\"p2\">Kolistin minimum inhibit\u00f6r konsantrasyon de\u011ferleri, ISO 20776-1:2019 SMD referans y\u00f6ntemi kullan\u0131larak belirlenmi\u015ftir (14). Ticari s\u0131v\u0131 mikrodil\u00fcsyon panelleri olan Sensititre\u2122 ve MIC COL, \u00fcretici firma talimatlar\u0131na g\u00f6re haz\u0131rlanm\u0131\u015ft\u0131r. Nordmann ve arkada\u015flar\u0131 (13) taraf\u0131ndan kolistin direncini taramak i\u00e7in geli\u015ftirilen SuperPolymyxin\u2122 agar tarama pla\u011f\u0131na benzer \u015fekilde 3.5 \u00b5g\/ml konsantrasyonda kolistin i\u00e7eren eozin metilen mavisi (EMB) agar\u0131 laboratuvar\u0131m\u0131zda haz\u0131rlanm\u0131\u015ft\u0131r (11). Kolistin direnci, daha \u00f6nce Jayol ve arkada\u015flar\u0131n\u0131n (12) tan\u0131mlad\u0131\u011f\u0131 \u015fekilde ara\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. Test edilecek bakteri 0.5 McFarland standard\u0131na ayarlanarak s\u00fcspansiyon haline getirilmi\u015f ve %0.9 NaCl i\u00e7inde 1\/10 oran\u0131nda dil\u00fce edilmi\u015ftir. Dil\u00fcsyondan, 10 mikrolitre al\u0131narak agar y\u00fczeyine inok\u00fcle edilmi\u015ftir. Plaklar 37 <sup>o<\/sup>C\u2019lik et\u00fcvde aerobik ko\u015fullarda ink\u00fcbe edilmi\u015ftir.<\/p>\n<p class=\"p2\">S\u0131v\u0131 mikrodil\u00fcsyon panelleri; 35\u00b11 <sup>o<\/sup>C\u2019de aerobik atmosferde, 16-20 saat ink\u00fcbasyon sonunda g\u00f6rsel olarak okunmu\u015ftur. \u00dcreme kontrol kuyucu\u011funda \u00fcreme olan ve atlamal\u0131 \u00fcreme olmayan (bir kuyucukta \u00fcreme olmazken daha y\u00fcksek konsantrasyonda antibiyotik i\u00e7eren kuyucukta \u00fcreme olmas\u0131) testler ge\u00e7erli kabul edilmi\u015ftir. SMD y\u00f6ntemi ve Sensititre\u2122 panelinde \u00fcreme, kuyucuklarda bulan\u0131kl\u0131k olu\u015fmas\u0131 ile de\u011ferlendirilmi\u015ftir. Kolorimetrik bir y\u00f6ntem olan MIC COL testinde ise \u00fcreme, kuyucuklardaki rengin maviden pembeye de\u011fi\u015fimi ile belirlenmi\u015ftir. EUCAST 2021, v.11.0 \u201cbreakpoint table\u201d s\u0131n\u0131r de\u011ferleri do\u011frultusunda, minimum inhibit\u00f6r konsantrasyonu (M\u0130K) de\u011feri \u22642 \u00b5g\/ml olan izolatlar duyarl\u0131, &gt;2 \u00b5g\/ml olan izolatlar ise diren\u00e7li olarak de\u011ferlendirilmi\u015ftir (4). Kolistin tarama agar\u0131na yap\u0131lan ekimler sonucundaki \u00fcremeler 24. ve 48. saatlerde g\u00f6rsel olarak de\u011ferlendirilmi\u015ftir. \u00dcreme olmas\u0131 izolat\u0131n kolistine diren\u00e7li oldu\u011fu, \u00fcreme olmamas\u0131 ise kolistine duyarl\u0131 oldu\u011fu \u015feklinde yorumlanm\u0131\u015ft\u0131r. Kalite kontrol i\u00e7in t\u00fcm deneylerde; <i>E. coli<\/i> ATCC 25922, <i>P. aeruginosa<\/i> ATCC 27853 ve <i>E. coli<\/i> NCTC 13846 (mcr-1 pozitif) izolatlar\u0131 kullan\u0131lm\u0131\u015ft\u0131r.<\/p>\n<h3 class=\"p3\">Sonu\u00e7lar\u0131n Analizi<\/h3>\n<p class=\"p2\">Her iki ticari sistemin referans y\u00f6ntem ile temel uyum (TU) ve kategorik uyum (KU) oranlar\u0131 ISO standardlar\u0131 temel al\u0131narak belirlenmi\u015ftir (14). KU, test edilen y\u00f6ntemin referans y\u00f6ntemle ayn\u0131 duyarl\u0131l\u0131k kategorisinde sonu\u00e7 vermesi [\u00f6rt\u00fc\u015fen (S, R) kategorik sonu\u00e7 say\u0131s\u0131]; TU ise belirlenen M\u0130K de\u011ferinin referans y\u00f6nteme g\u00f6re \u00b11 dil\u00fcsyonda olmas\u0131 olarak tan\u0131mlanm\u0131\u015ft\u0131r. TU hesaplan\u0131rken, referans y\u00f6ntem ve ticari panellerin konsantrasyon aral\u0131\u011f\u0131ndaki farkl\u0131l\u0131klar nedeniyle en y\u00fcksek ve en d\u00fc\u015f\u00fck M\u0130K de\u011ferleri uyumlu kabul edilmi\u015ftir. Testlerin \u201c\u00e7ok b\u00fcy\u00fck hata\u201d (\u00c7BH) ve \u201cb\u00fcy\u00fck hata\u201d (BH) oranlar\u0131 hesaplanm\u0131\u015ft\u0131r. \u00c7BH referans y\u00f6ntem ile diren\u00e7li bulunan bir izolat\u0131n test edilen y\u00f6ntem ile duyarl\u0131 bulunmas\u0131; BH ise referans y\u00f6ntem ile duyarl\u0131 bulunan bir izolat\u0131n test edilen y\u00f6ntem ile diren\u00e7li bulunmas\u0131 olarak tan\u0131mlanm\u0131\u015ft\u0131r (15).<\/p>\n<p class=\"p2\">\u00c7al\u0131\u015fmam\u0131z, Hacettepe \u00dcniversitesi Giri\u015fimsel Olmayan Klinik Ara\u015ft\u0131rmalar Etik Kurulu taraf\u0131ndan 20.10.2020 tarih ve 16969557-1526 say\u0131l\u0131 karar ile onaylanm\u0131\u015ft\u0131r.<\/p>\n<h2 class=\"p1\">BULGULAR<\/h2>\n<div id=\"attachment_24047\" style=\"width: 2195px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo2.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-24047\" class=\"size-full wp-image-24047\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo2.png\" alt=\"\" width=\"2185\" height=\"625\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo2.png 2185w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo2-390x112.png 390w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo2-810x232.png 810w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo2-768x220.png 768w\" sizes=\"auto, (max-width: 2185px) 100vw, 2185px\" \/><\/a><p id=\"caption-attachment-24047\" class=\"wp-caption-text\"><strong>Tablo 2.<\/strong> Kolistin S\u0131v\u0131 Mikrodil\u00fcsyon Panellerinin ve Kolistin Agar Tarama Pla\u011f\u0131n\u0131n \u00d6zellikleri<\/p><\/div>\n<div id=\"attachment_24049\" style=\"width: 2195px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo3.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-24049\" class=\"size-full wp-image-24049\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo3.png\" alt=\"\" width=\"2185\" height=\"1650\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo3.png 2185w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo3-344x260.png 344w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo3-715x540.png 715w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo3-768x580.png 768w\" sizes=\"auto, (max-width: 2185px) 100vw, 2185px\" \/><\/a><p id=\"caption-attachment-24049\" class=\"wp-caption-text\"><strong>Tablo 3.<\/strong> S\u0131v\u0131 Mikrodil\u00fcsyon Y\u00f6ntemleri ile Saptanan Minimum \u0130nhibit\u00f6r Konsantrasyon<br \/>De\u011ferlerinin Da\u011f\u0131l\u0131m\u0131<\/p><\/div>\n<div id=\"attachment_24051\" style=\"width: 2196px\" class=\"wp-caption alignright\"><a href=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo4.png\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-24051\" class=\"size-full wp-image-24051\" src=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo4.png\" alt=\"\" width=\"2186\" height=\"1244\" srcset=\"https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo4.png 2186w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo4-390x222.png 390w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo4-810x461.png 810w, https:\/\/www.klimikdergisi.org\/wp-content\/uploads\/2021\/12\/KD.C34.S3_3857_Tablo4-768x437.png 768w\" sizes=\"auto, (max-width: 2186px) 100vw, 2186px\" \/><\/a><p id=\"caption-attachment-24051\" class=\"wp-caption-text\"><strong>Tablo 4.<\/strong> Kolistin S\u0131v\u0131 Mikrodil\u00fcsyon Panellerinin ve Kolistin Agar Tarama Pla\u011f\u0131\u2019n\u0131n Performans\u0131<\/p><\/div>\n<p class=\"p2\"><i>In vitro<\/i> kolistin duyarl\u0131l\u0131k testinde kullan\u0131lan ticari panellerin (Sensititre\u2122 ve MIC COL) ve SMD y\u00f6nteminin genel \u00f6zellikleri Tablo 2\u2019de g\u00f6sterilmi\u015ftir. SMD y\u00f6ntemiyle 218 izolat\u0131n 42 (%19.3)\u2019si [<i>K. pneumoniae <\/i>(n=26)<i>, A. baumannii-calcoaceticus <\/i>kompleksi<i> <\/i>(n=9)<i>, P. aeruginosa <\/i>(n=6)<i>, K. aerogenes <\/i>(n=1)] kolistine diren\u00e7li bulunmu\u015ftur. SMD, Sensititre\u2122 ve MIC COL y\u00f6ntemleri ile elde edilen kolistin M\u0130K da\u011f\u0131l\u0131mlar\u0131 Tablo 3\u2019te verilmi\u015ftir.<\/p>\n<p class=\"p2\"><span class=\"s2\">Test edilen y\u00f6ntemlerin; KU, TU, \u00c7BH ve BH oranlar\u0131 hesaplanarak referans y\u00f6nteme g\u00f6re performans\u0131 Tablo 4\u2019te g\u00f6sterilmi\u015ftir. TU yaln\u0131zca s\u0131v\u0131 mikrodil\u00fcsyon temelli y\u00f6ntemler i\u00e7in hesaplanm\u0131\u015ft\u0131r. Ticari panellerin TU oranlar\u0131 t\u00fcm izolatlar i\u00e7in %85\u2019in \u00fczerinde bulunmu\u015ftur. <i>Klebsiella<\/i> spp., <i>A. baumannii-calcoaceticus <\/i>kompleksi ve <i>Pseudomonas<\/i> spp. i\u00e7in Sensititre\u2122 panelinin SMD y\u00f6ntemi ile TU oran\u0131 s\u0131ras\u0131yla %88.2, %90.4 ve %85.7; MIC COL testinin<span class=\"Apple-converted-space\">\u00a0 <\/span>SMD y\u00f6ntemi ile TU oran\u0131 ise %88.2, % 86.7 ve % 88.1 olarak tespit edilmi\u015ftir. MIC COL testi ile be\u015f <i>A. baumannii-calcoaceticus <\/i>kompleksi ve \u00fc\u00e7 <i>Pseudomonas<\/i> spp. izolat\u0131nda \u00c7BH tespit edilmi\u015ftir. Sensititre\u2122 y\u00f6ntemiyle ise iki <i>Klebsiella<\/i> spp. ve bir <i>A. baumannii-calcoaceticus <\/i>kompleksi izolat\u0131nda \u00c7BH saptanm\u0131\u015ft\u0131r.<\/span><\/p>\n<p class=\"p2\"><i>Pseudomonas <\/i>spp. d\u0131\u015f\u0131ndaki izolatlarda t\u00fcm y\u00f6ntemlerin, SMD y\u00f6ntemi ile KU oranlar\u0131 %90\u2019\u0131n \u00fczerinde saptanm\u0131\u015ft\u0131r. <i>Pseudomonas<\/i> spp. izolatlar\u0131nda; MIC COL, Sensititre\u2122 ve agar tarama testi 24\/48 saat KU\u2019lar\u0131 s\u0131ras\u0131yla %92.8, %80.9, %92.8 \/ %80.9 bulunmu\u015ftur. Agar tarama testinin 24 ve 48 saatlik sonu\u00e7lar\u0131 kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda 48. saatte de\u011ferlendirme yapman\u0131n <i>P. aeruginosa<\/i>\u2019da \u00c7BH oran\u0131n\u0131 azaltt\u0131\u011f\u0131 ancak BH oran\u0131n\u0131 artt\u0131rd\u0131\u011f\u0131 tespit edilmi\u015ftir.<\/p>\n<h2 class=\"p1\">\u0130RDELEME<\/h2>\n<p class=\"p2\">Kolistin, \u00f6zellikle karbapeneme diren\u00e7li Gram-negatif bakteri infeksiyonlar\u0131n\u0131n tedavisinde kullan\u0131lan antibiyotiklerden biridir. Artan kolistin kullan\u0131m\u0131, kazan\u0131lm\u0131\u015f kolistin direnci art\u0131\u015f\u0131na neden olmu\u015ftur (17-19). Kolistine duyarl\u0131l\u0131k testlerinde en \u00f6nemli g\u00fc\u00e7l\u00fck duyarl\u0131l\u0131\u011f\u0131n belirlenmesindeki sorunlard\u0131r. Referans y\u00f6ntem olarak s\u0131v\u0131 mikrodil\u00fcsyon \u00f6nerilmektedir; ancak bu y\u00f6ntemin, uygulanmas\u0131ndaki zorluklardan dolay\u0131, rutinde kullan\u0131m\u0131 s\u0131n\u0131rl\u0131d\u0131r. S\u0131v\u0131 mikrodil\u00fcsyon temelli, pratik uygulamas\u0131 kolay bir\u00e7ok ticari \u00fcr\u00fcn kullan\u0131ma girmi\u015ftir.<\/p>\n<p class=\"p2\">EUCAST Geli\u015ftirme Laboratuvar\u0131\u2019n\u0131n 75 Gram-negatif bakteri ile yapt\u0131\u011f\u0131 \u00e7al\u0131\u015fmada Sensititre\u2122 panelinin s\u0131v\u0131 mikrodil\u00fcsyon ile KU oran\u0131 %95, TU oran\u0131 %96 bulunmu\u015ftur. Bu \u00e7al\u0131\u015fmada Sensititre\u2122 panelinin BH oran\u0131 %10.2 iken \u00c7BH saptanmam\u0131\u015ft\u0131r (10). Jayol ve arkada\u015flar\u0131 (11), 185 Gram-negatif bakteride Sensititre\u2122 panelinin KU oran\u0131n\u0131 %97.8, \u00c7BH oran\u0131n\u0131 %3 bulmu\u015ftur. Chew ve arkada\u015flar\u0131n\u0131n (20) ara\u015ft\u0131rmas\u0131nda, 76 <i>Enterobacterales<\/i> izolat\u0131nda Sensititre\u2122 panelinin KU oran\u0131 %90.1, TU oran\u0131 %89.5, \u00c7BH oran\u0131 %4, BH oran\u0131 %11.8 saptanm\u0131\u015ft\u0131r. Yusuf ve arkada\u015flar\u0131n\u0131n (12), 70 gram negatif bakteri ile yapt\u0131klar\u0131 \u00e7al\u0131\u015fmada Sensititre\u2122 panelinin s\u0131v\u0131 mikrodil\u00fcsyon ile KU oran\u0131 %93, TU oran\u0131 %87, \u00c7BH oran\u0131 %14.7 saptanm\u0131\u015ft\u0131r. T\u00fcrkiye\u2019de Kansak ve arkada\u015flar\u0131n\u0131n (21) yapt\u0131\u011f\u0131 \u00e7al\u0131\u015fmada 38 <i>K. pneumoniae<\/i> izolat\u0131nda Sensititre\u2122 panelinin KU oran\u0131 %97, TU oran\u0131 %74 bulunmu\u015ftur. \u00c7al\u0131\u015fmam\u0131zda karbapenem diren\u00e7li Gram-negatif bakterilerde Sensititre\u2122 panelinin referans y\u00f6ntem ile KU oran\u0131 %94.9, TU oran\u0131 %89 oranlar\u0131nda saptan\u0131rken; \u00c7BH ve BH oranlar\u0131 s\u0131ras\u0131 ile %7.1 ve<span class=\"Apple-converted-space\">\u00a0 <\/span>%4.5 olarak tespit edilmi\u015ftir.<\/p>\n<p class=\"p2\">\u00c7al\u0131\u015fmam\u0131zda Sensititre\u2122 paneli ile BH sadece <i>P. aeruginosa<\/i> izolat\u0131nda saptanm\u0131\u015f olup bu izolatlar incelendi\u011finde, M\u0130K de\u011ferlerinin 4 \u00b5g\/ml oldu\u011fu ve referans y\u00f6ntemle aras\u0131nda \u00b11 ya da \u00b12 dil\u00fcsyon oldu\u011fu tespit edilmi\u015ftir. M\u0130K de\u011feri s\u0131n\u0131r de\u011fere yakla\u015ft\u0131k\u00e7a \u00c7BH ya da BH oranlar\u0131n\u0131n artt\u0131\u011f\u0131 di\u011fer \u00e7al\u0131\u015fmalarda da rapor edilmi\u015ftir (10). Bunun bir nedeni rehberlerde kolistin s\u0131n\u0131r de\u011ferlerinde orta (\u201cintermediate\u201d) kategorinin olmamas\u0131d\u0131r. EUCAST 2021, v. 11.0 \u201cbreakpoint table\u201d\u0131n son versiyonunda kolistin s\u0131n\u0131r de\u011ferleri de\u011fi\u015fmemekle birlikte, <i>P. aeruginosa<\/i>\u2019da M\u0130K=4 de\u011feri teknik belirsizlik alan\u0131 olarak g\u00fcncellenmi\u015ftir. EUCAST bu durumda testin ayn\u0131 y\u00f6ntemle veya farkl\u0131 bir y\u00f6ntemle tekrarlanmas\u0131n\u0131 \u00f6nermektedir. \u00c7al\u0131\u015fmam\u0131zda bu izolatlar\u0131n testleri tekrarlanm\u0131\u015f ancak M\u0130K de\u011ferleri ayn\u0131 bulunmu\u015ftur.<\/p>\n<p class=\"p2\"><span class=\"s2\">MIC COL testinde, mikroplaklar ayr\u0131labilen \u015feritlerden olu\u015fmaktad\u0131r. Test edilecek izolat say\u0131s\u0131 kadar \u015ferit mikroplaktan ayr\u0131larak, izolat say\u0131s\u0131n\u0131n belli bir say\u0131ya ula\u015fmas\u0131n\u0131 beklemeden ve gecikme olmadan \u00e7al\u0131\u015f\u0131labilmesi bir avantaj olu\u015fturmaktad\u0131r. MIC COL testinin kolorimetrik bir y\u00f6ntem olmas\u0131 de\u011ferlendirmede kolayl\u0131k sa\u011flamaktad\u0131r. Fakat di\u011fer kolorimetrik y\u00f6ntemlerde de oldu\u011fu gibi ara renkler de\u011ferlendirmede zorluk olu\u015fturabilmektedir. Literat\u00fcrde ticari MIC COL testinin de\u011ferlendirildi\u011fi \u00e7al\u0131\u015fma say\u0131s\u0131 s\u0131n\u0131rl\u0131d\u0131r. Bosacka ve arkada\u015flar\u0131n\u0131n (22) yapt\u0131klar\u0131 \u00e7al\u0131\u015fmada MIC COL testinin SMD y\u00f6ntemiyle KU oran\u0131 <i>Enterobacterales<\/i>\u2019de %100 olarak saptan\u0131rken bu oran nonfermentatif bakterilerde %83.3 olarak tespit edilmi\u015ftir. Ayn\u0131 \u00e7al\u0131\u015fmada MIC COL testine ek olarak, MIC-Strip Colistin (Merlin, Almanya), Microlatest MIC Colistin (Erba Lachema, \u00c7ek Cumhuriyeti), Sensitest Colistin (Liofilchem, \u0130talya), Phoenix (Becton Dickinson, ABD) and WalkAway (Beckman Coulter, ABD) y\u00f6ntemleri de\u011ferlendirilmi\u015f ve nonfermentatif basiller i\u00e7in TU oranlar\u0131n\u0131n %33.3 &#8211; % 66.7 aras\u0131nda de\u011fi\u015fti\u011fi belirtilmi\u015ftir (22). Bu \u00e7al\u0131\u015fmaya benzer olarak bizim \u00e7al\u0131\u015fmam\u0131zda <i>Klebsiella<\/i> spp.\u2019de y\u00fcksek TU ve KU oranlar\u0131 saptan\u0131rken \u00c7BH ve BH saptanmam\u0131\u015ft\u0131r. <i>Pseudomonas<\/i> spp. ve <i>A. baumannii-calcoaceticus <\/i>kompleksi<i> <\/i>izolatlar\u0131nda KU, TU ve \u00c7BH oranlar\u0131 s\u0131ras\u0131yla %92.8 \/ %94, %88.1 \/ %86.7 ve %50 \/ %55.5 olarak saptanm\u0131\u015ft\u0131r. \u00c7al\u0131\u015fmam\u0131zda MIC COL testinin, Bosacka ve arkada\u015flar\u0131n\u0131n (22) \u00e7al\u0131\u015fmalar\u0131na benzer \u015fekilde, <i>Klebsiella<\/i> spp.\u2019de kullan\u0131lmas\u0131n\u0131n uygun oldu\u011fu saptanm\u0131\u015f olmakla birlikte nonfermentatif basillerde \u00c7BH oranlar\u0131n\u0131n y\u00fcksekli\u011fi nedeniyle dikkatli kullan\u0131lmal\u0131d\u0131r. <\/span><\/p>\n<p class=\"p2\"><i>Klebsiella<\/i> spp. izolatlar\u0131nda, MIC COL ve Sensititre\u2122 y\u00f6ntemlerinin KU oranlar\u0131 kabul edilebilir olmakla birlikte, TU oranlar\u0131 %88.2 olarak saptanm\u0131\u015ft\u0131r. <i>A. baumannii- calcoaceticus<\/i> kompleksi izolatlar\u0131nda da KU oranlar\u0131 kabul edilebilir olarak tespit edilmi\u015ftir. Sensititre\u2122 ayn\u0131 anda sekiz izolat\u0131n kolistin duyarl\u0131l\u0131\u011f\u0131n\u0131n \u00e7al\u0131\u015f\u0131lmas\u0131 i\u00e7in tasarlanm\u0131\u015f bir mikroplakt\u0131r. Bu nedenle y\u00fcksek \u00f6rnek say\u0131s\u0131na sahip laboratuvarlar i\u00e7in tercih edilebilir. Sensititre\u2122 panelinin MIC COL\u2019a g\u00f6re test etti\u011fi konsantrasyon aral\u0131\u011f\u0131n\u0131n daha geni\u015f olmas\u0131 da bir avantajd\u0131r.<\/p>\n<p class=\"p2\">Germ ve arkada\u015flar\u0131n\u0131n (23) \u201cin-house\u201d olarak haz\u0131rlanm\u0131\u015f oldu\u011fu SuperPolymyxin agar ve 700 <i>Enterobacterales<\/i> izolat\u0131 ile yapt\u0131klar\u0131 \u00e7al\u0131\u015fmada, agar\u0131n kolistin direncini saptamadaki duyarl\u0131l\u0131\u011f\u0131 % 87.5 ve \u00f6zg\u00fcll\u00fc\u011f\u00fc %99.5 olarak tespit edilmi\u015ftir. Jayol ve arkada\u015flar\u0131n\u0131n (16) yapt\u0131\u011f\u0131 bir \u00e7al\u0131\u015fmada ise ticari SuperPolymyxin\u2122 agar\u0131n, <i>E. coli ve K. pneumoniae<\/i> izolatlar\u0131nda kolistin direncini saptamada duyarl\u0131l\u0131\u011f\u0131 ve \u00f6zg\u00fcll\u00fc\u011f\u00fc %100 bulunurken; <i>P. aeruginosa<\/i> izolatlar\u0131nda duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fck s\u0131ras\u0131 ile %100, %88.9; <i>A. baumannii <\/i>izolatlar\u0131nda ise<i> <\/i>s\u0131ras\u0131yla %92.3, %100 oranlar\u0131nda bulunmu\u015ftur. \u00c7al\u0131\u015fmam\u0131zda kulland\u0131\u011f\u0131m\u0131z SuperPolymyxin\u2122 agar ile ayn\u0131 konsantrasyonda kolistin i\u00e7eren kolistin agar tarama pla\u011f\u0131n\u0131n test edilen izolatlarda referans y\u00f6ntem ile KU oran\u0131 y\u00fcksek bulunmu\u015ftur. Fakat <i>Pseudomonas <\/i>spp.\u2019de \u00c7BH ve BH oran\u0131n\u0131n da y\u00fcksek oldu\u011fu saptanm\u0131\u015ft\u0131r.<span class=\"Apple-converted-space\">\u00a0 <\/span>Kolistin agar tarama pla\u011f\u0131 uygulamas\u0131 basit ve pratik bir y\u00f6ntemdir. Ancak M\u0130K de\u011feri saptanamamas\u0131 gibi bir dezavantaj\u0131 bulunmaktad\u0131r.<\/p>\n<p class=\"p2\">\u00c7al\u0131\u015fmam\u0131zda, Karbapenem diren\u00e7li Gram negatif bakterilerde kolistin duyarl\u0131l\u0131\u011f\u0131n\u0131n saptanmas\u0131 amac\u0131yla ticari Sensititre\u2122, MIC COL ve kolistin agar tarama pla\u011f\u0131 sonu\u00e7lar\u0131 SMD y\u00f6ntemiyle kar\u015f\u0131la\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. Test etti\u011fimiz y\u00f6ntemlerin KU oranlar\u0131n\u0131n kabul edilebilir s\u0131n\u0131rlarda oldu\u011fu (&gt;%90), ancak nonfermentatif bakterilerde \u00c7BH ve BH oranlar\u0131n\u0131n y\u00fcksek oldu\u011fu saptanm\u0131\u015ft\u0131r. \u00d6zellikle nonfermentatif bakterilerde uygunsuz kolistin tedavisine sebep olmamak i\u00e7in kolistin duyarl\u0131l\u0131\u011f\u0131n\u0131n bu y\u00f6ntemler ile belirlenmesinde daha dikkatli olunmas\u0131, sonu\u00e7lar\u0131n referans metotla do\u011frulanmas\u0131 gerekmektedir.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>G\u0130R\u0130\u015e Kolistin, Gram-negatif bakterilere kar\u015f\u0131 geni\u015f spektrumlu aktiviteye sahip polipeptid bir antibiyotiktir. Nefrotoksik ve n\u00f6rotoksik yan etkileri nedeniyle ge\u00e7mi\u015fte kullan\u0131m\u0131 s\u0131n\u0131rland\u0131r\u0131lm\u0131\u015ft\u0131r. Son y\u0131llarda, \u00e7oklu ve yayg\u0131n ila\u00e7 direnci g\u00f6steren Gram-negatiflerin prevalans\u0131n\u0131n artmas\u0131 nedeniyle bu bakteriler ile geli\u015fen infeksiyonlarda son se\u00e7enek antibiyotik olarak kolistin kullan\u0131m\u0131 artm\u0131\u015ft\u0131r (1). Fakat kullan\u0131m\u0131n\u0131n artmas\u0131na ba\u011fl\u0131 olarak bakterilerde kolistin direncinde art\u0131\u015f [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[5129],"tags":[5310,4303,5314,5313,5312,5311],"class_list":["post-23791","post","type-post","status-publish","format-standard","hentry","category-ozgun-arastirma","tag-duyarlilik-testi","tag-kolistin","tag-kolistin-agar-tarama","tag-mic-col","tag-sensititre","tag-sivi-mikrodilusyon"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/23791","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/comments?post=23791"}],"version-history":[{"count":3,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/23791\/revisions"}],"predecessor-version":[{"id":24190,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/23791\/revisions\/24190"}],"wp:attachment":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/media?parent=23791"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/categories?post=23791"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/tags?post=23791"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}