Journal of Global Antimicrobial Resistance (Mar 2023)

Evaluation of ceftolozane-tazobactam susceptibility on a French nationwide collection of Enterobacterales

  • Agnès B. Jousset,
  • Sandrine Bernabeu,
  • Cécile Emeraud,
  • Rémy A. Bonnin,
  • Alexandra Lomont,
  • Jean Ralph Zahar,
  • Audrey Merens,
  • Christophe Isnard,
  • Nathalie Soismier,
  • Eric Farfour,
  • Vincent Fihman,
  • Nicolas Yin,
  • Olivier Barraud,
  • Hervé Jacquier,
  • Anne-Gaëlle Ranc,
  • Frédéric Laurent,
  • Stéphane Corvec,
  • Louise Ruffier d'Epenoux,
  • Emmanuelle Bille,
  • Nicolas Degand,
  • Chloé Plouzeau,
  • Thomas Guillard,
  • Vincent Cattoir,
  • Asaf Mizrahi,
  • Antoine Grillon,
  • Frédéric Janvier,
  • Cécile Le Brun,
  • Marlène Amara,
  • Mathilda Bastide,
  • Alban Lemonnier,
  • Laurent Dortet

Journal volume & issue
Vol. 32
pp. 78 – 84

Abstract

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ABSTRACT: Objectives: Ceftolozane-tazobactam (C/T) proved its efficacy for the treatment of infections caused by non-carbapenemase producing Pseudomonas aeruginosa and Enterobacterales. Here, we aimed to provide susceptibility data on a large series of Enterobacterales since the revision of EUCAST categorization breakpoints in 2020. Methods: First, C/T susceptibility was determined on characterized Enterobacterales resistant to third generation cephalosporins (3GCs) (extended spectrum β-lactamase [ESBL] production or different levels of AmpC overexpression) (n = 213) and carbapenem-resistant Enterobacterales (CRE) (n = 259), including 170 carbapenemase producers (CPE). Then, 1632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by E-test® (biomérieux) and broth microdilution (BMD) (Sensititre™, Thermo Scientific) to perform method comparison. Results: Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with important variation depending on the resistance mechanism: 93% vs. 13% susceptibility for CTX-M and SHV-ESBL producers, respectively. Only 20% of the CRE were susceptible to C/T. Among CPE, 80% of OXA-48-like producers were susceptible to C/T, whereas all metallo-β-lactamase producers were resistant. The prospective study revealed that 95.6% of clinical isolates were susceptible to C/T. Method comparison performed on these 1632 clinical isolates demonstrated 99% of categorization agreement between MIC to C/T determined by E-test® in comparison with the BMD (reference) and only 74% of essential agreement. Conclusion: Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers, and ESBL-producing Escherichia coli but is less active against ESBL-producing Klebsiella pneumoniae, and CRE. E-test® led to an underestimation of the MICs in comparison to the BMD reference.

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