β- Laktamazların MALDI-TOF MS ile Saptanması

Yeşim Beşli

doi:10.37609/akya.4089

Yazarlar

Yeşim Beşli

https://orcid.org/0000-0003-4574-6036

DOI: https://doi.org/10.37609/akya.4089.c5943

Özet

Bu derleme, β–laktamazların Matriks Destekli Uçuş Zamanlı Kütle Spektrometris (MALDI-TOF MS) ile saptanmasına ilişkin güncel yaklaşımları ve klinik önemini özetlemektedir. β-laktam antibiyotik direncinin başlıca mekanizması olan β-laktamaz üretimi, tedavi seçeneklerini kısıtlamakta ve mortaliteyi artırmaktadır. MALDI-TOF, hidroliz temelli pik kaybı analizi, dirençle ilişkili biyobelirteçlerin tanımlanması, çeşitli özel protokoller veya doğrudan plaka üzerinde mikrodamlacık üreme (DOT-MGA) esaslı yöntemler aracılığıyla hızlı direnç belirteci saptanmasına olanak verir. Literatürde, Ambler sınıfı C β-laktamaz (AmpC), Genişlemiş Spektrumlu β-Laktamaz (GSBL) ve karbapenemazların saptanmasında duyarlılık/özgüllük değerlerinin çoğunlukla %85–100 aralığında olduğu, bazı protokollerde 30 dakikaya varan dönüş süreleri elde edildiği bildirilmiştir. Bu performans, ampirik geniş spektrumlu tedaviden hedefe yönelik tedaviye daha erken geçişi ve izolasyon önlemlerinin zamanında başlatılmasını destekleyebilir. Bununla birlikte, yöntemler arasında protokol, substrat ve inkübasyon farklılıkları nedeniyle heterojenlik sürmekte; düşük kaynaklı laboratuvarlarda maliyet ve cihaz boyutu uygulamayı sınırlayabilmektedir. Gelecekte, yapay zekâ destekli analizler, genişletilmiş referans spektrum veritabanları ve genomik entegrasyonun klinik yararı büyütmesi beklenmektedir. Standartlaştırma, çok merkezli validasyon ve klinik etkili müdahale çalışmaları öncelikli gereksinimlerdir.

This review synthesizes current approaches and clinical significance of detecting β -lactamases with matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF). β-lactamase production, the leading mechanism of β-lactam resistance, narrows therapeutic options and worsens outcomes. MALDI-TOF enables rapid resistance readouts via hydrolysis-based peak loss analysis, detection of resistance-associated biomarkers, specific protocols, and the direct-on-target microdroplet growth assay (DOT-MGA). Across studies, sensitivity/specificity for Ambler class C β-lactamase (AmpC), Extended-spectrum β-lactamases (ESBLs), and carbapenemases mostly falls within 85–100%, with turnaround times as short as 30 minutes. Such performance may support earlier transition from broad-spectrum empiric therapy to targeted therapy and timelier implementation of isolation measures. However, heterogeneity across protocols, substrates, and incubation conditions limits comparability; costs and instrument footprint constrain adoption in resource-limited laboratories. Analytical pitfalls persist: matrix effects, sample preparation requirements, and the influence of antibiotic choice (ceftriaxone, cefepime, carbapenems) and inhibitors (EDTA) on false results. Future directions include AI-assisted spectra interpretation, expanded reference libraries capturing rare and regional pathogens, and integration with high-resolution mass analyzers and genomics. Standardization, external validation, and outcome-oriented implementation studies are critical to translate MALDI-TOF-based resistance testing into consistent clinical benefit.

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