In vitro potency of novel ertapenem/zidebactam combination (WCK 6777) against carbapenemase-producing Enterobacterales collected across India.

Authors

Yamuna Devi Bakthavatchalam, Robert Bonomo, Adrian Egli, Rosmi Puthan, Abirami Shankar, Soniya Krishnamoorthy, Vasant Nagvekar, Rajni Sabharwal Ekadashi, Sudharsana J, Sneha Rajan, Camilla Rodrigues, Rangineni Jayaprada, Abi Manesh, Balaji Veeraraghavan

Published in

JAC-antimicrobial resistance. Volume 8. Issue 5. Pages dlag167. Epub Sep 07, 2026.

Abstract

Ertapenem is well suited for outpatient parenteral antimicrobial therapy (OPAT) due to its once-daily dosing and favourable safety profile; however, increasing enzyme-mediated resistance limits its clinical utility. Ertapenem/zidebactam (WCK 6777) is a novel β-lactam/β-lactam enhancer combination in which zidebactam exhibits high-affinity binding to penicillin-binding protein 2 (PBP2), augmenting ertapenem activity and overcoming β-lactamase-mediated resistance. We evaluated the in vitro activity of ertapenem/zidebactam against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae clinical isolates from India.
MICs of ertapenem/zidebactam and comparator agents (carbapenems, imipenem/relebactam, ceftazidime/avibactam and aztreonam/avibactam) were determined by broth microdilution method. Carbapenemase genes and PBP3 insertions were identified using PCR.
Ertapenem/zidebactam demonstrated potent activity against E. coli, inhibiting 99.5% of isolates at the PK/PD breakpoint of ≤8 mg/L (MIC₉₀, 0.5 mg/L), including NDM producers with PBP3 insertions. Against K. pneumoniae, susceptibility reached 93.6% among NDM producers and 88.5% among dual carbapenemase producers at the same breakpoint. Comparator agents showed variable activity, with limited efficacy against metallo-β-lactamase producers.
The enhanced activity of ertapenem/zidebactam is attributed to zidebactam's dual mechanism, β-lactamase inhibition and high-affinity PBP2 binding, enabling effective coverage despite complex resistance mechanisms. Its once-daily dosing supports its potential as an OPAT-enabling therapeutic option and warrant further clinical development.

PMID:
42703604
Bibliographic data and abstract were imported from PubMed on 07 Sep 2026.

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