{"id":22254,"date":"2021-04-30T18:11:28","date_gmt":"2021-04-30T15:11:28","guid":{"rendered":"https:\/\/www.klimikdergisi.org\/?p=22254"},"modified":"2021-06-02T13:39:03","modified_gmt":"2021-06-02T10:39:03","slug":"yogun-bakim-unitesinde-klebsiella-pneumoniae-infeksiyonlari-ve-karbapenem-direncine-etki-eden-risk-faktorleri","status":"publish","type":"post","link":"https:\/\/www.klimikdergisi.org\/tr\/2021\/04\/30\/yogun-bakim-unitesinde-klebsiella-pneumoniae-infeksiyonlari-ve-karbapenem-direncine-etki-eden-risk-faktorleri\/","title":{"rendered":"Yo\u011fun Bak\u0131m \u00dcnitesinde Klebsiella pneumoniae<\/i> \u0130nfeksiyonlar\u0131 ve Karbapenem Direncine Etki Eden Risk Fakt\u00f6rleri"},"content":{"rendered":"

G\u0130R\u0130\u015e<\/b><\/h2>\n

Klebsiella pneumoniae, Enterobacteriaceae<\/i> ailesinin bir \u00fcyesi olup toplum kaynakl\u0131 infeksiyonlar\u0131n yan\u0131 s\u0131ra hastane infeksiyonlar\u0131n\u0131n da \u00f6nemli etkenlerinden biridir (1). Yo\u011fun bak\u0131m \u00fcniteleri (YB\u00dc)\u2019nde de pn\u00f6moni ve bakteriyemilerin \u00f6nemli bir k\u0131sm\u0131ndan sorumludur. \u00d6zellikle son 10 y\u0131lda geni\u015flemi\u015f spektrumlu \u03b2-laktamaz (GSBL) \u00fcreten K. pneumoniae<\/i> su\u015flar\u0131n\u0131n artmas\u0131yla birlikte bu infeksiyonlarda karbapenemlerin ilk se\u00e7enek olarak kullan\u0131lmas\u0131 yayg\u0131nla\u015fm\u0131\u015f olup bu da beraberinde diren\u00e7 geli\u015fiminin artmas\u0131na neden olmaktad\u0131r (2). 2014 y\u0131l\u0131nda yay\u0131mlanan Global Diren\u00e7 Raporu’nda K. pneumonia<\/i>e\u2019de karbapenem direnci D\u00fcnya Sa\u011fl\u0131k \u00d6rg\u00fct\u00fc (World Health Organization \u2013 WHO)<\/span> taraf\u0131ndan %50\u2019nin \u00fczerinde bildirilmi\u015ftir (3). WHO CAESAR 2018 raporunda ise T\u00fcrkiye\u2019de kan ve beyin omurilik s\u0131v\u0131s\u0131 izolatlar\u0131nda K. pneumoniae<\/i>\u2019deki ertapenem direnci %43, imipenem\/meropenem direnci ise %38 olarak bildirilmi\u015ftir (4). YB\u00dc\u2019lerde K. pneumoniae<\/i> su\u015flar\u0131nda karbapenem direncinin artmas\u0131 ciddi tedavi sorunlar\u0131na neden olmakla beraber mortaliteyi ve morbiditeyi art\u0131rd\u0131\u011f\u0131 da bildirilmektedir (5,6). Antimikrobiyal diren\u00e7 profilleri hastaneden hastaneye, hatta klinikler aras\u0131nda bile farkl\u0131l\u0131k g\u00f6sterebilmektedir. Bu \u00e7al\u0131\u015fmada hastanemizde YB\u00dc\u2019de geli\u015fen K. pneumoniae<\/i> infeksiyonlar\u0131n\u0131n irdelenmesi, karbapenem direnci oranlar\u0131n\u0131n y\u0131llar i\u00e7indeki da\u011f\u0131l\u0131m\u0131 ve dirence etki eden risk fakt\u00f6rlerinin belirlenmesi ama\u00e7lanm\u0131\u015ft\u0131r.<\/p>\n

Y\u00d6NTEMLER<\/b><\/h2>\n

Ocak 2017-Ocak 2020 tarihleri aras\u0131nda hastanemizde YB\u00dc\u2019de yatm\u0131\u015f olan ve yat\u0131\u015ftan en az 48 saat sonra K. pneumoniae <\/i>etkenli hastane infeksiyonu (H\u0130) geli\u015fen 18 ya\u015f \u00fcst\u00fc hastalar \u00e7al\u0131\u015fmaya dahil edildi. Hastalara ait bilgiler bilgisayar kay\u0131tlar\u0131ndan ve \u0130nfeksiyon Kontrol Komitesi verilerinden geriye d\u00f6n\u00fck olarak kaydedildi. Hastalar\u0131n demografik \u00f6zellikleri, altta yatan hastal\u0131klar\u0131, \u201cAcute Physiology and Chronic Health Evaluation\u201d (APACHE) II ve \u201cSequential Organ Failure Assessment\u201d (SOFA) skorlar\u0131, yo\u011fun bak\u0131m biriminde uygulanan invazif i\u015flemler, yo\u011fun bak\u0131m biriminde yat\u0131\u015f s\u00fcreleri, ald\u0131\u011f\u0131 antimikrobikler kaydedildi. H\u0130 tan\u0131s\u0131 konulmas\u0131nda, \u201cCenters for Disease Control and Prevention\u201d (CDC) taraf\u0131ndan belirlenen tan\u0131mlamalar esas al\u0131nd\u0131 (7). Birden fazla K. pneumoniae<\/i> infeksiyonu geli\u015fen hastalarda ilk infeksiyon ata\u011f\u0131 \u00e7al\u0131\u015fmaya dahil edildi. H\u0130 geli\u015fti\u011fi d\u00fc\u015f\u00fcn\u00fclen hastalardan kan k\u00fclt\u00fcr\u00fcyle birlikte infeksiyon odaklar\u0131ndan (idrar, derin trakeal aspirat, kateter ucu vb.) k\u00fclt\u00fcrler al\u0131narak identifikasyon ve antibiyotik duyarl\u0131l\u0131k testleri yap\u0131ld\u0131. Kan k\u00fclt\u00fcrleri BD BACTEC\u2122 FX40 (Becton Dickinson Co., Sparks, MD, ABD) otomatik kan k\u00fclt\u00fcr\u00fc sisteminde ink\u00fcbe edildi. \u00dcreme sinyali veren \u00f6rnekler %5 koyun kanl\u0131 agar, \u201ceosin methylene blue\u201d (EMB) ve \u00e7ikolatams\u0131 agara, idrar \u00f6rnekleri %5 koyun kanl\u0131 agar ve EMB agara, bronkoalveolar lavaj (BAL) ve endotrakeal aspirat (ETA) \u00f6rnekleri ise %5 koyun kanl\u0131 agar, EMB ve \u00e7ikolata agara ekilerek 37\u00b0C de 24-48 saat ink\u00fcbe edildi. Besiyerlerinde \u00fcreme g\u00f6zlenen mikroorganizmalar\u0131n tan\u0131mlanmas\u0131nda konvansiyonel y\u00f6ntemler ve Phoenix\u2122 (Becton Dickinson Co., Sparks, MD, ABD) tam otomatize sistemi kullan\u0131ld\u0131. Karbapenem ve kolistin duyarl\u0131l\u0131\u011f\u0131 s\u0131v\u0131 mikrodil\u00fcsyon y\u00f6ntemiyle \u201cEuropean Committee on Antimicrobial Susceptibility Testing\u201d (EUCAST) standartlar\u0131na g\u00f6re saptand\u0131 (8). \u0130statistiksel veriler IBM SPSS Statistics for Windows, Version 25.0. (IBM Corp., Armonk, NY) program\u0131 kullan\u0131larak olu\u015fturuldu. Veriler s\u0131kl\u0131k, y\u00fczde oran, medyan, aritmetik ortalama, standart sapma hesaplanarak tan\u0131mland\u0131. Kesikli de\u011fi\u015fkenler \u03c72 ve Fisher\u2019in kesin testi kullan\u0131larak de\u011ferlendirildi. Tek de\u011fi\u015fkenli analizde anlaml\u0131 bulunan de\u011fi\u015fkenler \u00e7ok de\u011fi\u015fkenli testlerden lojistik regresyon kullan\u0131larak analiz edildi. S\u00fcrekli de\u011fi\u015fkenlerin normal da\u011f\u0131l\u0131ma uygunlu\u011fu Kolmogorov-Smirnov y\u00f6ntemiyle test edildi. Normal da\u011f\u0131l\u0131ma uyan de\u011fi\u015fkenler Student t<\/i>-testi, uymayanlar Mann-Whitney U <\/i>testiyle de\u011ferlendirildi. \u0130statistiksel olarak p<\/i> de\u011feri \u22640.05 i\u00e7in anlaml\u0131 kabul edildi.<\/span><\/p>\n

BULGULAR<\/b><\/h2>\n

\u00c7al\u0131\u015fma s\u00fcresince 78 hastada\u00a0K. pneumoniae<\/i>\u2019nin etken oldu\u011fu H\u0130 geli\u015fti. Bunlar\u0131n 20\u2019si 2017, 23\u2019\u00fc 2018, 35\u2019i de 2019 y\u0131l\u0131nda g\u00f6r\u00fcld\u00fc. Ya\u015f ortalamas\u0131 55.47\u00b118.7 olan 78 hastan\u0131n %64.1 (n=50)\u2019i erkek, %35.9 (n=28)\u2019u kad\u0131nd\u0131. Hastalar\u0131n 30 (%38.5)\u2019unun\u00a0<\/i>yo\u011fun bak\u0131m \u00f6ncesi bir ba\u015fka klinikte 48 saatten fazla yat\u0131\u015f \u00f6yk\u00fcs\u00fc vard\u0131.\u00a0K. pneumoniae<\/i>\u00a0infeksiyonlar\u0131n\u0131n da\u011f\u0131l\u0131m\u0131na bak\u0131ld\u0131\u011f\u0131nda ilk s\u0131rada primer kan dola\u015f\u0131m\u0131 infeksiyonu (KD\u0130) (n=40, %51.3) yer al\u0131rken bunu pn\u00f6moni (n=32, %41) ve \u00fcriner sistem infeksiyonlar\u0131 (\u00dcS\u0130) (n=6, %7.7) izledi. KD\u0130\u2019nin %52.5\u2019i santral ven\u00f6z kateterle ili\u015fkili kan dola\u015f\u0131m\u0131 infeksiyonu (SVK-KD\u0130), %47.5\u2019i de laboratuvarla do\u011frulanm\u0131\u015f KD\u0130 olarak saptand\u0131. Pn\u00f6moni g\u00f6r\u00fclen hastalar\u0131n da %81.2 (n=26)\u2019si ventilat\u00f6rle ili\u015fkili pn\u00f6moni (V\u0130P), %18.75\u2019 i (n=6) nozokomiyal pn\u00f6moni olarak de\u011ferlendirildi. Alt\u0131 hastada sekonder KD\u0130 saptand\u0131. Bu 6 hastan\u0131n 5\u2019inde V\u0130P tan\u0131s\u0131 ald\u0131ktan sonra, birinde de nozokomiyal pn\u00f6moni sonras\u0131 ayn\u0131 etkenle sekonder KD\u0130 geli\u015fti. \u00dcS\u0130\u2019lerin hepsi \u00fcriner kateterle ili\u015fkiliydi ve hi\u00e7birinde sekonder KD\u0130 geli\u015fmedi.<\/p>\n

\"\"<\/a>

\u015eekil 1. <\/strong>Yo\u011fun bak\u0131m \u00fcnitesinde K. pneumoniae <\/i>infeksiyonlar\u0131n\u0131n y\u0131llara g\u00f6re da\u011f\u0131l\u0131m\u0131.<\/p><\/div>\n

\u0130nfeksiyon t\u00fcrlerinin y\u0131llara g\u00f6re da\u011f\u0131l\u0131m\u0131na bak\u0131ld\u0131\u011f\u0131nda her \u00fc\u00e7 y\u0131lda da KD\u0130 birinci s\u0131kl\u0131kta g\u00f6r\u00fclmekle birlikte y\u0131llar i\u00e7inde KD\u0130 oran\u0131nda giderek azalma olurken pn\u00f6moni oranlar\u0131n\u0131n artma e\u011filiminde oldu\u011fu saptand\u0131 (\u015eekil 1). KD\u0130\u2019ler aras\u0131nda ise dikkat \u00e7ekici olarak SVK-KD\u0130 oranlar\u0131n\u0131n y\u0131llar i\u00e7inde artt\u0131\u011f\u0131 g\u00f6r\u00fcld\u00fc. 2017 y\u0131l\u0131nda t\u00fcm KD\u0130\u2019nin i\u00e7inde SVK-KD\u0130 oran\u0131 %33.3 iken 2019\u2019a gelindi\u011finde bu oran %62.5 olarak saptand\u0131. \u00dcS\u0130 oranlar\u0131na bak\u0131ld\u0131\u011f\u0131nda 2018 y\u0131l\u0131nda\u00a0K. pneumoniae<\/i>\u00a0etkenli \u00dcS\u0130 g\u00f6r\u00fclmezken di\u011fer 2 y\u0131lda benzer oranlarda oldu\u011fu g\u00f6r\u00fcld\u00fc.<\/span><\/p>\n

\"\"<\/a>

\u015eekil 2. <\/strong>K. pneumoniae infeksiyonlar\u0131nda y\u0131llara g\u00f6re karbapenem ve kolistin direnci oranlar\u0131.<\/p><\/div>\n

\"\"<\/a>

Tablo 1.<\/strong> Karbapeneme Diren\u00e7li ile \u0130li\u015fkili Risk Fakt\u00f6rleri<\/p><\/div>\n

Hastalar\u0131n 41 (%52.6)\u2019inde K. pneumoniae<\/i>\u00a0su\u015flar\u0131 karbapeneme diren\u00e7li, 14\u2019\u00fcnde (%17.9) ise kolistine diren\u00e7li bulundu. Direncin y\u0131llara g\u00f6re da\u011f\u0131l\u0131m\u0131na bak\u0131ld\u0131\u011f\u0131nda karbapenem direncinin 2017 y\u0131l\u0131nda %35 iken 2019 y\u0131l\u0131nda %62.9\u2019a y\u00fckseldi\u011fi, kolistin direncinin de %5\u2019ten %25.7\u2019ye y\u00fckseldi\u011fi g\u00f6r\u00fcld\u00fc (\u015eekil 2). \u0130nfeksiyon t\u00fcrlerine g\u00f6re karbapenem direnci de\u011ferlendirildi\u011finde; V\u0130P tan\u0131s\u0131 alan hastalarda karbapenem direnci %69.2 (18\/26), KD\u0130 olan hastalarda ise %47.5 (19\/40) olarak saptand\u0131. Karbapenem direncine etki eden risk fakt\u00f6rlerini irdelemek ama\u00e7l\u0131 karbapeneme diren\u00e7li ve duyarl\u0131\u00a0K. pneumoniae<\/i>\u00a0infeksiyonu olan hastalar kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131. Cinsiyet, ya\u015f ortalamas\u0131, altta yatan hastal\u0131klar a\u00e7\u0131s\u0131ndan iki grup aras\u0131nda istatistiksel olarak anlaml\u0131 fark saptanmad\u0131. Tek de\u011fi\u015fkenli analizde karbapeneme diren\u00e7li olan grupta YB\u00dc\u2019de yat\u0131\u015f s\u00fcresi (p=<\/i>0.003) ve yat\u0131\u015ftan K. pneumoniae<\/i> infeksiyonu geli\u015fene kadar ge\u00e7en s\u00fcre (p<<\/i>0.001) daha uzun saptand\u0131. Ayr\u0131ca K. pneumoniae<\/i> infeksiyonu \u00f6ncesinde ba\u015fka bir etkenle H\u0130 geli\u015fmi\u015f olmas\u0131 (p=<\/i>0.001 \u201codds\u201d oran\u0131 [OR]: 6.09, %95 g\u00fcven aral\u0131\u011f\u0131 [GA]: 1.98-18.75) ve \u00f6nceden karbapenem (p<<\/i>0.001 OR: 7.29 %95, GA: 2.49-21.31) ve vankomisin (p=<\/i>0.02 OR: 3.66, %95 GA: 1.25-10.69) kullan\u0131m\u0131 karbapeneme diren\u00e7li grupta anlaml\u0131 olarak daha y\u00fcksek bulundu. Bunun d\u0131\u015f\u0131nda hastada V\u0130P geli\u015fmi\u015f olmas\u0131 da tek de\u011fi\u015fkenli analizde karbapenem direnci a\u00e7\u0131s\u0131ndan istatistiksel olarak anlaml\u0131 bulundu (p=<\/i>0.04 OR: 2.83, %95 GA: 1.04-7.68). \u00c7ok de\u011fi\u015fkenli analiz y\u00f6ntemlerinden lojistik regresyon analizi uygulanarak yap\u0131lan de\u011ferlendirilmede karbapenem direnci a\u00e7\u0131s\u0131ndan ba\u011f\u0131ms\u0131z risk fakt\u00f6rleri daha \u00f6nceden ba\u015fka bir etkenle H\u0130 geli\u015fmi\u015f olmas\u0131 (p=<\/i>0.005, OR: 8.70, %95 GA: 1.91-39.65), K. pneumoniae<\/i> infeksiyonu \u00f6ncesi karbapenem kullan\u0131m\u0131 (p=<\/i>0.008, OR: 8.45, %95 GA: 1.76-40.64) ve total parenteral n\u00fctrisyon (TPN) uygulamas\u0131 (p=<\/i>0.04, OR: 4.2, %95 GA: 1.06-16.67) olarak saptand\u0131. Tablo 1\u2019de her iki grubun risk fakt\u00f6rleri a\u00e7\u0131s\u0131ndan kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131 ve tek de\u011fi\u015fkenli ve \u00e7ok de\u011fi\u015fkenli analiz sonu\u00e7lar\u0131 g\u00f6sterilmi\u015ftir.<\/p>\n

\u0130RDELEME<\/b><\/h2>\n

G\u00fcn\u00fcm\u00fczde H\u0130\u2019de Gram-negatif bakterilerin yeri giderek artmakta olup \u00e7ok ilaca diren\u00e7li Gram-negatif bakteriler YB\u00dc\u2019lerde hayat\u0131 tehdit eden infeksiyonlara neden olmaktad\u0131r. Bu etkenlerin ve diren\u00e7 profillerinin farkl\u0131l\u0131klar g\u00f6sterebildi\u011fi bilinmektedir. YB\u00dc\u2019lerdeki hastane infeksiyonlar\u0131n\u0131 tan\u0131mlamak, etken mikroorganizmalar\u0131 ve diren\u00e7 durumlar\u0131n\u0131 belirlemek, ampirik tedavi yakla\u015f\u0131m\u0131 ve bu infeksiyonlar\u0131n do\u011fru y\u00f6netimi a\u00e7\u0131s\u0131ndan olduk\u00e7a \u00f6nemlidir (9). Son y\u0131llarda s\u0131kl\u0131\u011f\u0131 giderek artan ve YB\u00dc\u2019de sorun te\u015fkil etmeye ba\u015flayan K. pneumoniae<\/i> infeksiyonlar\u0131n\u0131n artan diren\u00e7 oranlar\u0131yla mortalitenin ili\u015fkili oldu\u011funa dair yay\u0131nlar vard\u0131r (10-12).<\/p>\n

\u00c7al\u0131\u015fmam\u0131zda YB\u00dc\u2019de 3 y\u0131ll\u0131k s\u00fcre i\u00e7inde K. pneumoniae<\/i>\u2019n\u0131n etken oldu\u011fu H\u0130\u2019lerin giderek artt\u0131\u011f\u0131 ve infeksiyon t\u00fcrlerinden KD\u0130\u2019lerin en s\u0131k oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Bununla birlikte K. pneumoniae<\/i> infeksiyonlar\u0131n\u0131n y\u0131llara g\u00f6re da\u011f\u0131l\u0131m\u0131na bak\u0131ld\u0131\u011f\u0131nda KD\u0130 oran\u0131n\u0131n azald\u0131\u011f\u0131 buna kar\u015f\u0131n pn\u00f6monilerin oran\u0131n\u0131n artt\u0131\u011f\u0131 saptanm\u0131\u015ft\u0131r (\u015eekil 1). KD\u0130\u2019lerin da\u011f\u0131l\u0131m\u0131na bak\u0131ld\u0131\u011f\u0131nda ise KD\u0130\u2019lerin oran\u0131nda giderek azalma g\u00f6zlense de bunlar\u0131n i\u00e7inde SVK-KD\u0130 oranlar\u0131nda \u00fc\u00e7 y\u0131l i\u00e7inde art\u0131\u015f oldu\u011fu dikkat \u00e7ekmektedir. Bu bulgular hastanemizde YB\u00dc\u2019de <\/span>\u00f6zellikle V\u0130P ve kateterle ili\u015fkili KD\u0130\u2019lerin azalt\u0131lmas\u0131na y\u00f6nelik infeksiyon kontrol \u00f6nlemlerinin al\u0131nmas\u0131, kateter bak\u0131mlar\u0131na \u00f6zen g\u00f6sterilmesi ve bu konuda personel e\u011fitimlerinin art\u0131r\u0131lmas\u0131 gerekti\u011fini g\u00f6stermi\u015ftir.<\/p>\n

Karbapeneme diren\u00e7li K. pneumoniae<\/i> ilk kez Amerika\u2019da 1997\u2019de, \u00fclkemizde de 2001 y\u0131l\u0131nda bildirilmi\u015ftir (13,14). Karbapeneme diren\u00e7li K. pneumoniae<\/i> oranlar\u0131 t\u00fcm d\u00fcnyada giderek artmakta olup, do\u011fu Akdeniz \u00fclkelerinde ve Avrupa\u2019da %50\u2019nin \u00fczerine \u00e7\u0131kmaktad\u0131r (3,15). Hastal\u0131k Kontrol ve Korunma Merkezleri (Centers for Diseases Control and Prevention \u2013 CDC)<\/span> \u201cNational Healthcare Safety Network\u201d 2016 raporunda 2011-2014 y\u0131llar\u0131 aras\u0131ndaki karbapeneme diren\u00e7li K. pneumoniae <\/i>(KDKP) <\/i>oran\u0131 %3.3-10.9 olarak, Avrupa Antimikrobiyal Diren\u00e7 S\u00fcrveyans A\u011f\u0131 (European Antimicrobial Resistance Surveillance Network –<\/span>EARS-Net) 2017 raporunda ise Avrupa\u2019da K. pneumoniae<\/i>\u2019de karbapenem direnci ortalama %7.2 olarak bildirilmi\u015ftir (16). Ayn\u0131 raporda Avrupa\u2019da karbapenem direncinin en y\u00fcksek oldu\u011fu \u00fclkelerden Yunanistan\u2019da bu oran %64.7, \u0130talya\u2019da %29.7, Romanya\u2019da %22.5 olarak bildirilmi\u015ftir. \u00dclkemizdeki \u00e7al\u0131\u015fmalardan 2004-2005 y\u0131llar\u0131 aras\u0131nda yap\u0131lan H\u0130T\u0130T-1 s\u00fcrveyans \u00e7al\u0131\u015fmas\u0131nda, K pneumoniae<\/i>\u2019de imipenem direnci %1.3, 2007\u2019de yap\u0131lan H\u0130T\u0130T-2 \u00e7al\u0131\u015fmas\u0131nda %3.1 olarak bulunmu\u015ftur (17,18). G\u00fczel <\/span>Tun\u00e7can ve arkada\u015flar\u0131 (19) 2007-2008 y\u0131llar\u0131nda yapt\u0131klar\u0131 \u00e7al\u0131\u015fmada E. coli<\/i> ve Klebsiella<\/i> su\u015flar\u0131nda imipenem ve ertapenem direnci saptamam\u0131\u015flard\u0131r. \u0130stanbul\u2019da \u00fc\u00e7\u00fcnc\u00fc basamak bir YB\u00dc\u2019de 2004-2011 y\u0131llar\u0131 aras\u0131nda yap\u0131lan bir \u00e7al\u0131\u015fmada K. pneumoniae<\/i> izolatlar\u0131nda 2009 y\u0131l\u0131na kadar karbapenem direnci g\u00f6zlenmezken, 2011 y\u0131l\u0131nda bu oran\u0131n %20\u2019ye \u00e7\u0131kt\u0131\u011f\u0131 bildirilmi\u015ftir (20). Candevir Ulu ve arkada\u015flar\u0131 (21) YB\u00dc hastalar\u0131nda yapt\u0131klar\u0131 \u00e7al\u0131\u015fmada 2012 y\u0131l\u0131nda karbapenem direncini %48 bulmu\u015flard\u0131r. Temiz ve arkada\u015flar\u0131 (22) kan k\u00fclt\u00fcrlerinden izole ettikleri K. pneumoniae<\/i> izolatlar\u0131nda karbapenem direncini %20, Akg\u00fcl ve arkada\u015flar\u0131 (23) ise \u00e7al\u0131\u015fmalar\u0131nda 2014 y\u0131l\u0131nda K. pneumoniae <\/i>su\u015flar\u0131ndaki karbapenem direncinin %66.9\u2019a \u00e7\u0131kt\u0131\u011f\u0131n\u0131 bildirmi\u015flerdir. Bizim \u00e7al\u0131\u015fmam\u0131zda da YB\u00dc\u2019deki K. pneumoniae<\/i> infeksiyonlar\u0131nda karbapenem direnci %52.6 olarak saptanm\u0131\u015f olup 2017 y\u0131l\u0131nda %35 iken 2019 y\u0131l\u0131nda %62.9\u2019a y\u00fckseldi\u011fi g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Karbapeneme diren\u00e7li su\u015flar \u03b2-laktamlara in vitro<\/i> diren\u00e7li olup, s\u0131kl\u0131kla kinolon gruplar\u0131na da diren\u00e7 g\u00f6zlenmekte ve tedavi alternatifi olarak kolistin kullan\u0131lmaktad\u0131r. Karbapeneme diren\u00e7li Gram-negatif bakterilerde kolistinin yayg\u0131n kullan\u0131m\u0131yla K. pneumoniae<\/i> su\u015flar\u0131nda kolistin direnci de artmaya ba\u015flam\u0131\u015ft\u0131r (24,25). \u00d6zkul Ko\u00e7ak ve Haz\u0131rolan (26) 2018 y\u0131l\u0131nda yapt\u0131klar\u0131 \u00e7al\u0131\u015fmada karbapeneme diren\u00e7li 81 K. pneumoniae<\/i> izolat\u0131n\u0131n %39.5\u2019inin kolistine de diren\u00e7li oldu\u011funu saptam\u0131\u015flard\u0131r. Bizim \u00e7al\u0131\u015fmam\u0131zda da YB\u00dc\u2019deki K. pneumoniae<\/i> su\u015flar\u0131nda kolistin direncinin 3 y\u0131l i\u00e7inde %5\u2019ten %25.7\u2019ye y\u00fckseldi\u011fi, KDKP izolatlar\u0131nda da kolistin direncinin %34.1 oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr.<\/p>\n

Yap\u0131lan \u00e7al\u0131\u015fmalarda karbapenem direnci geli\u015fimini etkileyen bir\u00e7ok risk fakt\u00f6r\u00fc tan\u0131mlanm\u0131\u015ft\u0131r (27,28). Bu fakt\u00f6rler aras\u0131nda; hastanede yat\u0131\u015f \u00f6yk\u00fcs\u00fc, yo\u011fun bak\u0131mda yat\u0131\u015f, yat\u0131\u015f s\u00fcresinin uzunlu\u011fu, steroid kullan\u0131m\u0131, transplantasyon \u00f6yk\u00fcs\u00fc, mekanik ventilasyon, diyaliz uygulanmas\u0131, nazogastrik t\u00fcp, TPN, trakeostomi, \u00fcriner kateter, SVK gibi invazif i\u015flemler, \u00f6zellikle karbapenem ba\u015fta olmak \u00fczere kinolon, vankomisin, anti-Pseudomonas<\/i> antibiyotiklerin kullan\u0131m\u0131 bulunmaktad\u0131r. \u00c7o\u011fu \u00e7al\u0131\u015fmada ya\u015f ve cinsiyetin karbapenem direnci a\u00e7\u0131s\u0131ndan anlaml\u0131 de\u011fi\u015fkenler olmad\u0131\u011f\u0131 bildirilmi\u015ftir (11,22,29). \u00c7al\u0131\u015fmam\u0131zda da ya\u015f ortalamas\u0131 ve cinsiyet a\u00e7\u0131s\u0131ndan iki grup benzer bulunmu\u015f olup literat\u00fcrle uyumludur. Hastayla ili\u015fkili risk fakt\u00f6rlerinden altta yatan hastal\u0131klar a\u00e7\u0131s\u0131ndan da \u00e7al\u0131\u015fmam\u0131zda iki grup aras\u0131nda anlaml\u0131 fark g\u00f6r\u00fclmemi\u015ftir.<\/p>\n

\u0130nvazif giri\u015fimler normal v\u00fccut bariyerini bozdu\u011fu i\u00e7in mikroorganizmalar i\u00e7in bir giri\u015f kap\u0131s\u0131 olu\u015fturur ve diren\u00e7li patojenlerin biyofilm tabakas\u0131 olu\u015fturarak eradike edilmesini g\u00fc\u00e7le\u015ftirir. Yap\u0131lan bir\u00e7ok \u00e7al\u0131\u015fmada SVK, \u00fcriner kateter, trakeostomi, ent\u00fcbasyon, nazogastrik t\u00fcp gibi invazif giri\u015fimler KDKP infeksiyonlar\u0131 i\u00e7in risk fakt\u00f6r\u00fc olarak tan\u0131mlanm\u0131\u015ft\u0131r (21,22,27,28). \u0130nvazif giri\u015fimlerin karbapenem direncine etkisi a\u00e7\u0131s\u0131ndan tek de\u011fi\u015fkenli analizinde trakeostomi, transf\u00fczyon, TPN ve hemodiyaliz\/CRRT uygulanmas\u0131 oran\u0131 karbapeneme diren\u00e7li grupta daha y\u00fcksek bulunmas\u0131na kar\u015f\u0131n aradaki fark istatistiksel olarak anlaml\u0131 bulunmam\u0131\u015ft\u0131r. Bu durumun \u00e7al\u0131\u015fma dizayn\u0131yla ilgili olabilece\u011fi, \u00e7al\u0131\u015fmam\u0131z sadece YB\u00dc hastalar\u0131n\u0131 kapsad\u0131\u011f\u0131ndan hastalar\u0131n \u00e7o\u011funda bu invazif giri\u015fimlerin uygulan\u0131yor olmas\u0131ndan kaynakland\u0131\u011f\u0131 d\u00fc\u015f\u00fcn\u00fclm\u00fc\u015ft\u00fcr.<\/p>\n

Hastanede ve yo\u011fun bak\u0131mda yat\u0131\u015f s\u00fcresi de karbapenem direncini etkileyen fakt\u00f6rler aras\u0131ndad\u0131r. Yat\u0131\u015f s\u00fcresi uzad\u0131k\u00e7a hem invazif i\u015flemlere maruz kalma hem de antibiyotik kullan\u0131m oran\u0131 artmakta, bu da mikroorganizmalarda diren\u00e7 geli\u015fimini art\u0131rmaktad\u0131r. \u00c7al\u0131\u015fmam\u0131zda YB\u00dc\u2019de yat\u0131\u015f s\u00fcresi tek de\u011fi\u015fkenli analizde karbapeneme diren\u00e7li grupta anlaml\u0131 olarak daha uzun bulunmu\u015f olup (p=<\/i>0.003), \u00e7ok de\u011fi\u015fkenli analizde ise anlaml\u0131l\u0131\u011f\u0131n\u0131 yitirmi\u015ftir (p=<\/i>0.15). Benzer olarak, yat\u0131\u015ftan infeksiyon geli\u015fene kadar ge\u00e7en s\u00fcre karbapeneme diren\u00e7li olan grupta daha uzun saptanm\u0131\u015f ancak \u00e7ok de\u011fi\u015fkenli analizde anlaml\u0131 bulunmam\u0131\u015ft\u0131r (p=<\/i>0.76). Bir di\u011fer bulgu olarak tek de\u011fi\u015fkenli analizde karbapeneme diren\u00e7li ve duyarl\u0131 gruplar aras\u0131nda KD\u0130 oranlar\u0131 benzer iken V\u0130P oran\u0131n\u0131n diren\u00e7li grupta anlaml\u0131 olarak daha y\u00fcksek oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (p=<\/i>0.04) (Tablo 1). V\u0130P geli\u015fimi her ne kadar karbapenem direnci i\u00e7in ba\u011f\u0131ms\u0131z risk fakt\u00f6r\u00fc saptanmam\u0131\u015f olsa da V\u0130P tan\u0131s\u0131 alan olgular\u0131m\u0131zda karbapenem direncinin %70\u2019e kadar \u00e7\u0131km\u0131\u015f olmas\u0131 nedeniyle bu hastalarda \u00f6zellikle ba\u015flang\u0131\u00e7 tedavisine yan\u0131t al\u0131namad\u0131\u011f\u0131nda diren\u00e7 olas\u0131l\u0131\u011f\u0131 ak\u0131lda tutulmal\u0131d\u0131r. Benzer bir bulgu olarak; olgu-olgu-kontrol \u015feklinde yap\u0131lan ve karbapeneme diren\u00e7li ve duyarl\u0131 Gram-negatif bakteriyemili hastalar\u0131n ayn\u0131 d\u00f6nem YB\u00dc\u2019de yatan ve bakteriyemi geli\u015fmemi\u015f hastalarla kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131 bir \u00e7al\u0131\u015fmada da V\u0130P geli\u015fimi karbapeneme diren\u00e7li grup i\u00e7in ba\u011f\u0131ms\u0131z risk fakt\u00f6r\u00fc olarak bulunmu\u015ftur (30).<\/p>\n

APACHE II skorunun y\u00fcksek olmas\u0131n\u0131n YB\u00dc\u2019de diren\u00e7li Gram-negatif mikroorganizmalar\u0131n kolonizasyonu i\u00e7in risk fakt\u00f6r\u00fc oldu\u011fu bildirilmektedir (31). \u00c7al\u0131\u015fmam\u0131zda hastalar\u0131n ciddiyetinin de\u011ferlendirilmesi amac\u0131yla yat\u0131\u015f APACHE II ve SOFA skorlar\u0131 hesaplanarak \u00e7al\u0131\u015fmaya dahil edilmi\u015ftir. Bu skorlar\u0131n K. pneumoniae<\/i> infeksiyonlar\u0131nda karbapenem direncine etkilerine bak\u0131ld\u0131\u011f\u0131nda her iki grupta da skorlar birbirine yak\u0131n bulunmu\u015f olup istatistiksel olarak anlaml\u0131 olmad\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (p=<\/i>0.21, p=<\/i>0.49). Eser ve arkada\u015flar\u0131 (32)\u2019n\u0131n yapt\u0131\u011f\u0131 \u00e7al\u0131\u015fmada Charlson skoru, Glasgow koma skoru (GKS) ve APACHE II skorlar\u0131n\u0131n K. pneumoniae<\/i>\u2019da karbapenem direncine etkileri bulunmazken \u201cSimplified Acute Physiology Score\u201d (SAPS) II skoru KDKP infeksiyonu olan hastalarda anlaml\u0131 olarak daha y\u00fcksek saptanm\u0131\u015ft\u0131r.<\/p>\n

Geni\u015f spektrumlu antibiyotiklerin kullan\u0131m\u0131n\u0131n KDKP infeksiyonlar\u0131nda art\u0131\u015fa yol a\u00e7t\u0131\u011f\u0131 bilinmektedir (13,33-37). Bir meta-analizde karbapenem, aminoglikozid, glikopeptid, kinolon ve anti-Pseudomonas<\/i> antibiyotik kullan\u0131m\u0131n\u0131n karbapeneme diren\u00e7li infeksiyonlar\u0131n geli\u015fimi i\u00e7in risk te\u015fkil etti\u011fi bildirilmi\u015ftir (28). Antibiyotiklerin selektif olarak bask\u0131s\u0131 diren\u00e7li mikroorganizmalarla olan infeksiyonlar\u0131n temel nedenlerinden biridir. Karbapenem kullan\u0131m\u0131 da duyarl\u0131 olan su\u015flar\u0131n bask\u0131lanarak karbapeneme diren\u00e7li su\u015flar\u0131n se\u00e7ilmesine neden olabilmektedir. Karbapenem kullan\u0131m\u0131 bizim \u00e7al\u0131\u015fmam\u0131zda da literat\u00fcrle uyumlu olarak KDKP infeksiyonlar\u0131 i\u00e7in ba\u011f\u0131ms\u0131z risk fakt\u00f6r\u00fc olarak saptanm\u0131\u015f ve duyarl\u0131 olan gruba g\u00f6re diren\u00e7li grupta 8 kat fazla bulunmu\u015ftur (p=<\/i>0.008, OR: 8.45, %95 GA: 1.76-40.64). Vankomisin kullan\u0131m\u0131 karbapeneme diren\u00e7li grupta anlaml\u0131 olarak daha y\u00fcksek bulunmu\u015f olsa da \u00e7ok de\u011fi\u015fkenli analizde karbapenem direncini etkileyen ba\u011f\u0131ms\u0131z risk fakt\u00f6r\u00fc olarak saptanmam\u0131\u015ft\u0131r. Vankomisin kullan\u0131m\u0131 v\u00fccuttaki mikrofloran\u0131n dengesini bozarak Gram-negatif mikroorganizmalar\u0131n \u00e7o\u011falmas\u0131n\u0131, mutasyonlar\u0131n ve karbapenemazlar\u0131n yay\u0131l\u0131m\u0131n\u0131 art\u0131rabilir. Ayr\u0131ca YB\u00dc\u2019de yatan hastalar\u0131n hemen hepsi kritik hastalar oldu\u011fundan ampirik olarak ba\u015flanan antibiyotikler de geni\u015f spektrumlu olmakta, \u00f6zellikle de karbapenemle birlikte glikopeptid kombinasyonlar\u0131 s\u0131k kullan\u0131lmaktad\u0131r. Hastanemizde YB\u00dc\u2019de de karbapenemler ve vankomisin s\u0131k kullan\u0131lan antibiyotiklerden olup Klebsiella<\/i> su\u015flar\u0131nda karbapenem direncinin art\u0131\u015f\u0131na katk\u0131 yapt\u0131\u011f\u0131 d\u00fc\u015f\u00fcn\u00fclm\u00fc\u015ft\u00fcr. \u00c7al\u0131\u015fmam\u0131zda karbapenem kullan\u0131m\u0131 (p=<\/i>0.008, OR: 8.45, %95 GA: 1.76-40.64), daha \u00f6nceden ba\u015fka bir etkenle H\u0130 geli\u015fmi\u015f olmas\u0131 (p=<\/i>0.005, OR: 8.70, %95GA: 1.91-39.65) ve TPN uygulanmas\u0131 (p=<\/i>0.04, OR: 4.2, %95 GA: 1.06-16.67) KDKP infeksiyonlar\u0131nda ba\u011f\u0131ms\u0131z risk fakt\u00f6rleri olarak bulunmu\u015ftur. K. pneumoniae<\/i> infeksiyonu \u00f6ncesi ba\u015fka bir etkenle infeksiyon geli\u015fmi\u015f olmas\u0131n\u0131n da yine antibiyotiklere maruz kalma nedeniyle anlaml\u0131 oldu\u011fu d\u00fc\u015f\u00fcn\u00fclm\u00fc\u015ft\u00fcr.<\/p>\n

Yap\u0131lan \u00e7al\u0131\u015fmalarda karbapenem direncinin mortaliteyi art\u0131rd\u0131\u011f\u0131na dair bulgular mevcuttur (38). Karbapeneme diren\u00e7li ve duyarl\u0131 K. pneumoniae<\/i> infeksiyonlar\u0131n\u0131n kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131 \u00e7al\u0131\u015fmam\u0131zda mortalite oranlar\u0131 a\u00e7\u0131s\u0131ndan iki grup aras\u0131nda istatistiksel olarak anlaml\u0131 bir fark g\u00f6zlenmemi\u015ftir (p=<\/i>0.99, OR: 0.99, %95 GA: 0.40-2.42). \u00dclkemizden yap\u0131lan baz\u0131 \u00e7al\u0131\u015fmalarda da bizim \u00e7al\u0131\u015fmam\u0131za benzer olarak karbapeneme duyarl\u0131 ve diren\u00e7li K. pneumoniae<\/i> infeksiyonlar\u0131nda mortalite oranlar\u0131 birbirine yak\u0131n bulunmu\u015ftur (21,32).<\/p>\n

Sonu\u00e7 olarak, YB\u00dc\u2019de K. pneumoniae<\/i> etkenli hastane infeksiyonlar\u0131n\u0131n irdelendi\u011fi \u00e7al\u0131\u015fmam\u0131zda son 3 y\u0131la ait epidemiyolojik \u00f6zellikler, diren\u00e7 da\u011f\u0131l\u0131m\u0131 ve karbapenem direncini etkileyen risk fakt\u00f6rleri de\u011ferlendirilmi\u015f olup karbapenem kullan\u0131m\u0131n\u0131n diren\u00e7 geli\u015fiminde ba\u011f\u0131ms\u0131z risk fakt\u00f6r\u00fc olarak bulunmas\u0131, \u00fcnitemizde karbapenem kullan\u0131m\u0131n\u0131n k\u0131s\u0131tlanmas\u0131 gerekti\u011fi d\u00fc\u015f\u00fcnd\u00fcrm\u00fc\u015ft\u00fcr. Bu konuda daha fazla say\u0131da hastayla yap\u0131lan randomize kontroll\u00fc \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r. Her merkezin s\u0131kl\u0131k ve diren\u00e7 oranlar\u0131 konusunda kendi verilerini ortaya koymas\u0131 al\u0131nacak \u00f6nlemlerle infeksiyon oranlar\u0131n\u0131n azalt\u0131lmas\u0131, ampirik tedavi se\u00e7imi ve antibiyotik kullan\u0131m politikalar\u0131n\u0131n belirlenmesi a\u00e7\u0131s\u0131ndan \u00f6nem ta\u015f\u0131maktad\u0131r.<\/p>\n","protected":false},"excerpt":{"rendered":"

G\u0130R\u0130\u015e Klebsiella pneumoniae, Enterobacteriaceae ailesinin bir \u00fcyesi olup toplum kaynakl\u0131 infeksiyonlar\u0131n yan\u0131 s\u0131ra hastane infeksiyonlar\u0131n\u0131n da \u00f6nemli etkenlerinden biridir (1). Yo\u011fun bak\u0131m \u00fcniteleri (YB\u00dc)\u2019nde de pn\u00f6moni ve bakteriyemilerin \u00f6nemli bir k\u0131sm\u0131ndan sorumludur. \u00d6zellikle son 10 y\u0131lda geni\u015flemi\u015f spektrumlu \u03b2-laktamaz (GSBL) \u00fcreten K. pneumoniae su\u015flar\u0131n\u0131n artmas\u0131yla birlikte bu infeksiyonlarda karbapenemlerin ilk se\u00e7enek olarak kullan\u0131lmas\u0131 yayg\u0131nla\u015fm\u0131\u015f olup […]<\/p>\n","protected":false},"author":2,"featured_media":22716,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[5129],"tags":[4082,4383,5173,3474,3691],"class_list":["post-22254","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-ozgun-arastirma","tag-cogul-ilac-direnci","tag-karbapenemler","tag-klebsiella-pneumoniae-2","tag-risk-faktorleri","tag-yogun-bakim-uniteleri"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/22254","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=22254"}],"version-history":[{"count":4,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/22254\/revisions"}],"predecessor-version":[{"id":22845,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/22254\/revisions\/22845"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/media\/22716"}],"wp:attachment":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/media?parent=22254"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/categories?post=22254"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/tags?post=22254"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}