Karbapenemlere Direnç Mekanizmaları

Yazarlar

Hatice Hale Gümüş
https://orcid.org/0000-0001-9071-9606

Özet

Çok ilaca dirençli bakteri prevalansının tüm dünyada artmasının yanı sıra, son çare ilaçlar olarak kabul edilen karbapenemlere direncin de artması klinisyenlere sınırlı tedavi seçeneği bırakarak artmış mortalite ve morbidite riskine yol açmaktadır. Karbapenemlere direnç intrinsik olarak spesifik hedefin olmaması, sitoplazmik veya dış membranın kompozisyonunun geçirgenliğe izin vermemesi gibi sebepler ile bazı bakterilerde doğal olarak bulunmaktadır. Dahası, bir bakteride doğal direncin bulunması farklı direnç mekanizmalarını da kazanabilme riskini artırmaktadır. Kromozomlarda sonradan ortaya çıkan mutasyonlar veya mobil genler aracılığı ile bakterinin karbapenemlere direnç geliştirmesi ise, çeşitli mekanizmalar ile olmaktadır: karbapenemin bakteri dış membranından geçişinin azalması, porin kaybı, efluks pompaları ile hücre dışına atılması, ilacın hedef yapısındaki bağlanma noktalarının modifikasyonu ve etkinliğini inaktive eden hidrolitik enzimlerin (β-laktamazlar; Karbapenemazlar) üretilmesi.

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