Superior in vitro Activity of Cefepime-Enmetazobactam Over Ceftazidime-Avibactam and Piperacillin-Tazobactam Against 3rd Generation cephalosporin resistant Enterobacterales.

The rise of extended-spectrum β-lactamase (ESBL) and carbapenem-resistant Enterobacterales (CRE) has severely limited treatment options in India. Cefepime-enmetazobactam (FPE), a novel β-lactam/β-lactamase inhibitor combination approved by the US FDA in 2024, shows promise as a carbapenem-sparing agent. A total of 383 non-duplicate resistant isolates of Escherichia coli and Klebsiella pneumoniae subsp. pneumoniae. were studied (January 2023-December 2024) at a tertiary-care centre in New Delhi. Isolates were categorized as third generation cephalosporin resistant but carbapenem-susceptible (Group A, n=258) or carbapenem-resistant (Group B, n=125). Antimicrobial susceptibility was determined by CLSI disc diffusion, and synergy with aztreonam was evaluated. Among Group A isolates, FPE exhibited the highest activity-95.4% E. coli and 97.4% K. pneumoniae susceptibility-outperforming ceftazidime-avibactam (88.1% and 84.6%) and Piperacillin tazobactam (5.4% and 10.2%, respectively). In Group B (CRE), activity was significantly lower: FPE (13% E. coli, 14.3% K. pneumoniae), CZA (31.9% and 7.1%), and PT (0%). ESBL production was observed in 88% of Group A isolates, predominantly blaCTX-M (94%), while all CRE carried blaNDM and blaOXA-48 genes. FPE-aztreonam synergy was infrequent (≤4%). Cefepime-enmetazobactam demonstrated superior in vitro activity to CZA and Piperacillin Tazobactam against ESBL-producing but carbapenem-susceptible Enterobacterales, making it a potent carbapenem-sparing option.