Synergistic Activity of Ceftazidime-Avibactam-Aztreonam Combination Against Metallo-Betalactamase Producing Enterobacterales Isolates

Abstract

Introduction: Carbapenem-resistant Enterobacterales (CRE) pose a major therapeutic challenge due to diverse resistance mechanisms, particularly metallo-β-lactamases (MBLs) such as NDM, VIM, and IMP. Ceftazidime-avibactam (CZA) is ineffective against MBLs, while aztreonam (ATM) retains activity but is vulnerable to ESBLs and AmpC enzymes. The CZA–ATM combination offers a rational strategy to overcome these limitations.

Aim: To evaluate the synergistic activity of ceftazidime-avibactam and aztreonam against MBL-producing CRE isolates.

Methods: A cross-sectional study was conducted over four months in the Department of Microbiology, MGM Medical College & Hospital, Chh Sambhajinagar. Ninety-six CRE isolates from clinical specimens were identified using Vitek 2 Compact. Carbapenemase production was confirmed by Trurapid OKNVI Resist 5 kit. Synergy testing of CZA–ATM was performed using the Broth Disc Elution method.

Results: Of 96 CRE isolates, Klebsiella pneumoniae (47.9%) and Escherichia coli (31.3%) predominated. Carbapenemase profiling revealed OXA-48-like enzymes (44.8%) as most common, followed by MBLs (32.3%) and KPC (19.8%). Among 31 MBL-producing isolates, synergy with CZA–ATM was observed in 74.2%, with K. pneumoniae showing the highest response (69.6%). The majority of isolates were recovered from pus (39.6%) and urine (25%) specimens, with Medicine (29.2%) and Surgery (22.9%) departments contributing most cases.

Conclusion: The CZA–ATM combination demonstrated significant synergistic activity against MBL-producing CRE, particularly K. pneumoniae, restoring susceptibility in over 70% of isolates. These findings support its potential as a salvage therapy in clinical practice, though persistent resistance in a subset of strains underscores the need for continued surveillance and cautious application.