Öz
Giriş: Kolistin, karbapenem dirençli Acinetobacter baumannii kompleks (CR-ABC) enfeksiyonu olan hastalarda kullanılabilecek seçeneklerdendir, ancak son zamanlarda kolistin için de direnç ve heterodirenç bildirilmiştir. Bu çalışmada hastanemizde izole edilen CR-ABC suşlarında, kolistin heterojen direnç oranını ve kolistinin ve bu ilacın ikili kombinasyonlarının kolistin heterodirenç/direnç gelişimi üzerine etkilerini araştırmayı amaçladık.
Gereç ve Yöntem: Karbapenem dirençli A. baumannii izolatları vve standart ABC suşu [American Type Culture Collection (ATCC) 19606] üzerinde heterojen direnç analizi yapıldı. Gizli heterodirenç/direnci ortaya çıkarabilmek için, izolatlar sub-inhibitör konsantrasyonlarda kolistine maruz bırakıldı. Standart suş ve bir klinik izolat üzerinde kolistin için ‘time-kill’ çalışması yapıldı. İlaç kombinasyonlarının heterodirenç/direnç gelişimi üzerine etkilerini incelemek için seri pasaj deneyleri yapıldı.
Bulgular: Yapılan ilk heterodirenç analizinde hiçbir suşta heterodirenç saptanmadı. Ancak sonrasında sub-inhibitör dozda kolistine maruz bırakılan tüm izolatlarda kolistine heterodirenç/direnç gelişti. Seri pasajlarda, kolistin-rifampisin, kolistin-tigesiklin kombinasyonları sub-inhibitör dozda bile kolistin dirençli alt popülasyonların üremesini engelledi. Kolistin-gentamisin kombinasyonu ATCC suşu için etkili iken, klinik izolatta etkili olamadı. Kolistin-flukonazol kombinasyonu ise tüm dozlarda etkisiz bulundu.
Sonuç: Çalışmamızda heterojen dirençli gözükmeyen suşların, kolistin maruziyeti sonrasında kolayca heterodirençli/dirençli hale gelebilecekleri gösterildi. Kolistin-rifampisin, kolistin-tigesiklin kombinasyonlarının düşük dozlarda bile heterodirenç/direnç gelişimini engellediği saptandı. Kolistin-gentamisin kombinasyonu ise düşük dozlarda klinik izolatta etkisiz bulundu. Kolistin-flukonazol kombinasyonu dirençli bakteri oluşumunu önlemede etkisiz bulundu. Uygunsuz kolistin kullanımı ile bu antibiyotiğe karşı direnç/heterodirenç kolaylıkla gelişebilir. Bunu engellemek için kolistin, mutlaka uygun dozlarda ve önerilen antibiyotiklerle kombine olarak kullanılmalıdır.
Anahtar Kelimeler: Kolistin, karbapenem, kombinasyon, heterodirenç, rifampin
Kaynakça
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