In-vitro activity of cefepime/enmetazobactam against extended spectrum beta-lactamases and/or ampC producing Enterobacterales and Pseudomonas aeruginosa collected across India.

BACKGROUND: Extended spectrum beta-lactamase producing Enterobacterales are classified as critical priority pathogens with limited therapeutic options. Enmetazobactam is a novel penicillanic sulfone beta-lactamase inhibitor with the spectrum of coverage against range of ESBLs. The combination of cefepime/enmetazobactam has been approved for the treatment of cUTI including acute pyelonephritis in United States and Europe, and additionally licensed for the treatment of hospital acquired pneumonia including ventilator associated pneumonia and their associated bacteremia in Europe. In this study, we determined the in-vitro activity of cefepime/enmetazobactam along with comparators against molecularly well characterised third generation cephalosporin resistant Enterobacterales and P. aeruginosa isolates METHODS: Non-duplicate third generation cephalosporin resistant Enterobacterales (E. coli, n = 262; K. pneumoniae, n = 250; Enterobacter sp., n = 32; Proteus spp., n = 22) and P. aeruginosa (n = 100) clinical isolates were included in this study. Presence of ESBLs, ampCs and OXA-1 encoding genes were detected by PCR. MICs of cefepime/enmetazobactam and comparators were determined by reference broth microdilution. Time kill assay was performed to assess the antibacterial activity of cefepime/enmetazobactam against ESBL and/or ampC producers.

RESULTS: Cefepime/enmetazobactam potently inhibited all CTX-M and/or OXA-1 producing E. coli isolates at MIC of ≤ 2 mg/L and ampC (CMY and/or DHA) producing isolates at MIC of ≤ 4 mg/L. Among CTX-M producing E. coli, susceptibility to TZP was significantly dropped from 78% to 58% in the presence of OXA-1. Further, cefepime/enmetazobactam continued to show potent activity against CTX-M producing K. pneumoniae and were inhibited at MIC of ≤ 1 mg/L. All the tested P. aeruginosa isolates were highly susceptible to cefepime/enmetazobactam with 100% inhibition. In time-kill assay, cefepime/enmetazobactam showed ≥ 3 log10 kill against CTX-M producingE. coli and CTX-M producingK. pneumoniae isolates, which is comparable to that of meropenem.

CONCLUSION: The findings of the present study retraites that the spectrum of coverage of cefepime/enmetazobactam is superior to that of TZP and similar to that of meropenem, emphasising the importance of cefepime/enmetazobactam as a carbapenem-sparing option.