JAC-antimicrobial resistance · 2026
In vitro potency of novel ertapenem/zidebactam combination (WCK 6777) against carbapenemase-producing Enterobacterales collected across India.
СтатьяНазвание и аннотация: Перевод в очереди
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Bakthavatchalam Yamuna Devi, Bonomo Robert, Egli Adrian, Puthan Rosmi, Shankar Abirami, Krishnamoorthy Soniya, Nagvekar Vasant, Ekadashi Rajni Sabharwal, J Sudharsana, Rajan Sneha, Rodrigues Camilla, Jayaprada Rangineni, Manesh Abi, Veeraraghavan Balaji
Аннотация
BACKGROUND AND OBJECTIVES: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.