Glikopeptidlere Direnç Mekanizmaları
Özet
Son yıllarda antimikrobiyal direnç (AMD) acil bir küresel sağlık sorunu haline gelmiştir. Dünya Sağlık Örgütü insan sağlığını tehdit eden vankomisine dirençli Enterococcus faecium (E. faecium), vankomisine dirençli veya orta duyarlı Staphylococcus aereus (S. aureus) izolatlarını yüksek öncelikli patojenler olarak sınıflandırmıştır. Özellikle gelişmiş ülkelerde sorun haline gelen Clostridioides difficile (C. difficile) enfeksiyonlarının artması, yüksek mortalite ile seyretmesi ve tedavide ilk sıra ilaç olan vankomisin kullanımının artması yeni direnç sorunlarını gündeme getirmiştir. Glikopeptidlere direnç mekanizmaları, tek mekanizma olmamakla birlikte, E. faecium’da temel olarak “van” operon çeşitlerinin transpozonlar aracılığı ile kazanılması, S. aereus’da hücre duvarında monomerik D-Alanin-D-Alanin içeren hedeflerin birikmesi ile hücre duvarının kalınlaşması ve azalmış transpeptidasyon çapraz bağ aktivitesi ve Cl. difficile’de mutasyon ile hedef yapının değişmesi, biyofilm formasyonu ve spor oluşturması ile ilişkili bulunmuştur.
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