Genişlemiş Spektrumlu Beta-Laktamazlar GSBL ve Tanı Yöntemleri

Klasik TEM ve SHV türü enzimlerden nokta mutasyonu ile gelişmiş olan Genişlemiş Spektrumlu Beta-Laktamazlar GSBL , son 30 yılda önemli bir direnç mekanizması olarak ortaya çıkmış olup tanımlanan enzim sayısı 200’e ulaşmıştır. Bu enzimleri kodlayan genlerin çoğu plazmidler ile yayılım göstermekte ve genellikle beraberinde beta-laktam yapısında olmayan diğer antibiyotiklere karşı da direnç genleri taşımaktadır. En uygun tedavi seçeneklerinin belirlenmesi için Clinical and Laboratory Standards Institute CLSI ve diğer standart rehberlerde özellikle Escherichia coli ve Klebsiella pneumoniae izolatları için rutin olarak GSBL varlığının tarama ve doğrulama testleri ile araştırılması önerilmektedir. Bu amaçla geliştirilen testlerin çoğu üretilen enzimin klavulanik asit varlığında inhibisyonunun gözlenmesi esasına dayanır. Rutin laboratuar uygulamalarında yaygın olarak kullanılan Çift Disk Sinerji yöntemi, ucuz ve uygulaması kolay bir yöntem olarak tatmin edici sonuçlar vermektedir. Ancak bu testte sonuç alınması için en az 18-24 saat gerekmekte ve bazı enzim türleri saptanamayabilmektedir. Son yıllarda geliştirilen kromojenik testler ve moleküler yöntemlerle kısa sürede sonuç alınabilse de uygulama zorlukları nedeniyle yaygın kullanımları sınırlı kalmaktadır. Bu derlemede GSBL enzimlerinin klinik önemi, türleri ve in vitro tanıda kullanılan yöntemler üzerinde durulacaktır

Anahtar Kelimeler:

Direnç, GSBL, E. coli, K. pneumoniae

Extended Spectrum Beta-Lactamases ESBLs and Identification Methods

Extended Spectrum Beta-Lactamases ESBLs which develop from classic TEM and SHV beta-lactamases by point mutations have been emerged as significant resistance mechanisms for last 30 years, and their number has reached about 200. The most of the genes encoding these enzymes are transferred on the plasmids and they frequently co-transfer some genes that are responsible for the resistance to other antimicrobials which are not in beta-lactam structure. To select the most appropriate therapy choices, some guidelines including Clinical and Laboratory Standards Institute CLSI have recommended to routinely determine the production of ESBLs with applying screening and confirmative tests for Escherichia coli and Klebsiella pneumoniae isolates. Majority of the tests for ESBLs detection are based on the visualization of the enzyme inhibition in the presence of clavulonic acid. Double Disc Synergy test, one of the most widespreadly used in the routine laboratory interventions, is a cheap and easy-to-apply method, and gives satisfactory results. However, in this test, 18-24 hours are required to obtain the result, and some types of enzymes can not be identified. The chromogenic tests and molecular methods which are developed in the recent years may give result in a shorter time, but their usages are limited due to difficulties for application. In this review, clinical importance of ESBL enzymes, their types and in vitro diagnostic methods will be discussed

Keywords:

Resistance, ESBL, E. coli, K. pneumoniae,

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