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Synergy evaluation of cefepime/enmetazobactam in combination with novel β-lactam/β-lactamase inhibitor combinations (βL/βLICs) against Klebsiella pneumoniae carrying different blaKPC variants

The Journal of Antibiotics (2026)Cite this article

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Recently a novel β-lactam/β-lactam inhibitor combination (βL/βLIC), cefepime/enmetazobactam, has been approved by FDA and EMA since 2024 for the treatment of patients with complicated urinary tract infections (cUTI), hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), and for the treatment of patients with bacteremia due to extended spectrum β-lactamase (ESβL)-producing Enterobacterales [1]. Cefepime is a 4th-generation cephalosporin with a broad spectrum of bactericidal activity against gram-negative and gram-positive bacteria including pathogens producing AmpC, or OXA-48-like β-lactamase. Enmetazobactam, a tazobactam derivative with enhanced bacterial cell penetration, is a novel penicillanic acid sulphone (PAS) β-lactamase inhibitor showing potent inhibitor activity against ESBL class A β-lactamases, weak or variable activity against class C and D β-lactamases and no effect against class B β-lactamases [2].

In vitro studies demonstrated that cefepime-enmetazobactam has potent antibacterial activity against ESBL-producing, AmpC-producing and OXA-48 producing Enterobacterales instead activity against carbapenem-resistant Enterobacterales (CRE) is only rarely effective [1]. Although cefepime-enmetazobactam exhibited moderate antibacterial in vitro-effect against KPC-producers, recently studies suggested the possible use of this combination for treatment of infections due to KPC-producing strains resistant to ceftazidime-avibactam [1,2,3]. In this context, we recently demonstrated that cefepime-enmetazobactam showed high antibacterial activity against K. pneumoniae resistant to ceftazidime/avibactam due to mutated blaKPC gene [4].

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Funding

This work was supported by FUR2024 to Paolo Gaibani.

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Authors and Affiliations

  1. Department of Medicine, Università degli studi di Udine, Udine, Italy

    Carlo Tascini & Paolo Gaibani

  2. Infectious Diseases Unit, Azienda sanitaria universitaria Friuli Centrale, Udine, Italy

    Carlo Tascini

  3. Department of Diagnostic and Public Health, University of Verona, Verona, Italy

    Giulia Zocche

  4. Microbiology and Virology Unit, Department of Pathology, Azienda Ospedaliera Universitaria Integrata Di Verona, Verona, Italy

    Paolo Gaibani

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  1. Carlo Tascini
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Correspondence to Paolo Gaibani.

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Tascini, C., Zocche, G. & Gaibani, P. Synergy evaluation of cefepime/enmetazobactam in combination with novel β-lactam/β-lactamase inhibitor combinations (βL/βLICs) against Klebsiella pneumoniae carrying different blaKPC variants. J Antibiot (2026). https://doi.org/10.1038/s41429-026-00900-8

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