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

J Glob Antimicrob Resist. 2023 Mar:32:78-84. doi: 10.1016/j.jgar.2023.01.003. Epub 2023 Jan 26.

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.

Keywords: Carbapenemase; Ceftolozane-tazobactam; ESBL; Enterobacterales; Epidemiology; France; MIC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Cephalosporins / pharmacology
  • Cephalosporins / therapeutic use
  • Enterobacteriaceae / genetics
  • Escherichia coli
  • Humans
  • Prospective Studies
  • Pseudomonas Infections* / drug therapy
  • Pseudomonas aeruginosa
  • Tazobactam / pharmacology
  • Tazobactam / therapeutic use
  • beta-Lactamases / genetics

Substances

  • ceftolozane
  • Anti-Bacterial Agents
  • Cephalosporins
  • ceftolozane, tazobactam drug combination
  • Tazobactam
  • beta-Lactamases