Update of clinical application in ceftazidime-avibactam for multidrug-resistant Gram-negative bacteria infections

Abstract

Purpose: Multidrug-resistant Gram-negative bacteria (MDR-GNB) have become a major global public health threat. Ceftazidime-avibactam (CAZ-AVI) is a newer combination of β-lactam/β-lactamase inhibitor, with activity against carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). The aim of this review is to describe the recent real-world experience of CAZ-AVI for the infections due to MDR-GNB.

Methods: We searched PubMed, Embase and Google Scholar for clinical application in CAZ-AVI for MDR-GNB infections. Reference lists were reviewed and synthesized for narrative review.

Results: MDRGNB infections are associated with higher mortality significantly comparing to drug-susceptible bacterial infections. Fortunately, CAZ-AVI shows significant benefits for infections due to KPC or OXA-48 CRE, comparing to colistin, carbapenem, aminoglycoside and other older agents, even in those with immunocompromised status. The efficacy of CAZ-AVI varies in different infection sites due to CRE, which is lower in pneumonia. Early use is associated with improved clinical outcomes. Noteworthy, when adopted as salvage therapy, CAZ-AVI is still superior to other GNB active antibiotics. CAZ-AVI plus aztreonam is recommended as the first line of MBL-CRE infections. However, for infections caused by KPC- and OXA-48-producing isolates, further investigations are needed to demonstrate the benefit of combination therapy. Besides CRE, CAZ-AVI is also active to MDR-PA. However, the development of resistance in CRE and MDR-PA against CAZ-AVI is alarming, and more investigations and studies are needed to prevent, diagnose, and treat infections due to CAZ-AVI-resistant pathogens.

Conclusions: CAZ-AVI appears to be a valuable therapeutic option in MDR-GNB infections. Using CAZ-AVI appropriately to improve efficacy and decrease the emergence of resistance is important.

Keywords: Carbapenem-resistant Enterobacterales; Ceftazidime–avibactam; Multidrug-resistant Gram-negative bacteria; Multidrug-resistant Pseudomonas aeruginosa.