A New Therapeutic Option Against Metallo-β-Lactamase-Producing Gram-Negative Bacteria: Aztreonam-Avibactam

Yıl 2025, Cilt: 9 Sayı: 2, 62 - 73, 31.08.2025

Mervenur Demir

https://doi.org/10.34084/bshr.1750260

Öz

Aztreonam-avibactam (ATM-AVI) is a newly developed intravenous antibacterial agent targeting metallo-β-lactamase (MBL)-producing Gram-negative bacteria. It consists of a combination of aztreonam, a monobactam, and avibactam, a broad-spectrum β-lactamase inhibitor. This combination is specifically designed to enhance efficacy against multidrug-resistant Enterobacterales and other Gram-negative pathogens that co-produce MBLs and serine β-lactamases. While aztreonam retains stability against MBL enzymes, it can be inactivated by serine β-lactamases. Avibactam restores the activity of aztreonam by inhibiting Ambler class A, C, and certain class D β-lactamases. Clinical studies have demonstrated the efficacy and safety of the ATM-AVI combination in the treatment of complicated intraabdominal infections, hospital-acquired pneumonia, and infections with limited treatment options. The Phase III REVISIT and ASSEMBLE trials have reported promising outcomes, with high clinical success rates and low mortality. Approved by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), ATM-AVI is considered an alternative therapeutic option against carbapenem-resistant isolates. This review presents a comprehensive evaluation of the pharmacokinetic and pharmacodynamic properties, mechanism of action, susceptibility testing, clinical trials’ data, and potential applications of ATM-AVI.

Anahtar Kelimeler

Aztreonam , avibaktam , metallo-β-laktamaz , komplike intraabdominal enfeksiyon , antibiyotik direnci , Enterobacterales

Metallo-β-Laktamaz Üreten Gram-Negatif Bakterilere Karşı Yeni Bir Tedavi Seçeneği: Aztreonam-Avibaktam

Öz

Aztreonam-avibaktam (ATM-AVI), metallo-β-laktamaz (MBL) üreten Gram-negatif bakterilere karşı geliştirilmiş, intravenöz uygulanan yeni bir antibakteriyel ajan olup, monobaktam sınıfından aztreonam ile geniş spektrumlu bir β-laktamaz inhibitörü olan avibaktamın kombinasyonundan oluşmaktadır. Bu kombinasyon, özellikle MBL ve eş zamanlı olarak serin β-laktamazlar üreten çok ilaca dirençli Enterobacterales ve diğer Gram-negatif patojenlere karşı etkinliği artırmak amacıyla tasarlanmıştır. Aztreonam, MBL enzimlerine karşı stabilitesini korumasına rağmen, serin β-laktamazlar tarafından inaktive edilebilmektedir. Avibaktam ise Ambler sınıfı A, C ve bazı D β-laktamazları inhibe ederek aztreonamın bu enzimlere karşı etkinliğini yeniden kazandırmaktadır. Klinik çalışmalarda, ATM-AVI kombinasyonunun komplike intraabdominal enfeksiyonlar, hastane kaynaklı pnömoni ve sınırlı tedavi seçeneği bulunan enfeksiyonlarda etkili ve güvenli olduğu gösterilmiştir. Faz III REVISIT ve ASSEMBLE çalışmaları, bu ajanın yüksek klinik başarı oranları ve düşük mortalite ile umut vadeden sonuçlar sunduğunu ortaya koymuştur. Avrupa İlaç Ajansı (EMA) ve ABD Gıda ve İlaç Dairesi (FDA) tarafından onaylanmış olan ATM-AVI, karbapenemlere dirençli izolatlara karşı alternatif bir tedavi seçeneği olarak değerlendirilmektedir. Bu derlemede, ATM-AVI’nin farmakokinetik ve farmakodinamik özellikleri, etki mekanizması, duyarlılık testleri, klinik çalışmaların verileri ve potansiyel kullanımı ele alınmıştır.

Anahtar Kelimeler

Aztreonam , avibaktam , metallo-β-laktamaz , komplike intraabdominal enfeksiyon , antibiyotik direnci , Enterobacterales

Etik Beyan

Derleme çalışması olduğundan etik kurul izni alınmamıştır.

Destekleyen Kurum

Herhangi bir finansal destek alınmamıştır.

Kaynakça

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