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

Abstract

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 againstcarbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Theaim of this review is to describe the recent real-world experience of CAZ-AVI for the infections due to MDR-GNB. We searched PubMed, Embase and Google Scholar for clinical application in CAZ-AVI forMDR-GNB infections. Reference lists were reviewed and synthesized for narrative review. MDRGNBinfections 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 efficacyof CAZ-AVI varies in different infection sites due to CRE, which is lower in pneumonia. Early use is associated withimproved clinical outcomes. Noteworthy, when adopted as salvage therapy, CAZ-AVI is still superior to other GNBactive antibiotics. CAZ-AVI plus aztreonam is recommended as the first line of MBL-CRE infections. However, forinfections caused by KPC- and OXA-48-producing isolates, further investigations are needed to demonstrate thebenefit of combination therapy. Besides CRE, CAZ-AVI is also active to MDR-PA. However, the development ofresistance in CRE and MDR-PA against CAZ-AVI is alarming, and more investigations and studies are needed toprevent, diagnose, and treat infections due to CAZ-AVI-resistant pathogens. CAZ-AVIappears to be a valuable therapeutic option in MDR-GNB infections. Using CAZ-AVI appropriately to improveefficacy and decrease the emergence of resistance is important.