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

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 break-points in 2020.Methods: First, C/T susceptibility was determined on characterized Enterobacterales resistant to third generation cephalosporins (3GCs) (extended spectrum beta-lactamase [ESBL] production or different levels of AmpC overexpression) (n = 213) and carbapenem-resistant Enterobacterales (CRE) (n = 259), includ-ing 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 (R) (biomerieux) and broth microdilution (BMD) (SensititreTM, Thermo Scientific) to perform method comparison.Results: Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with impor-tant 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-,B-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 (R) 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 (R) led to an underestimation of the MICs in comparison to the BMD reference.(c) 2023 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Automated summary

This study aimed to provide susceptibility data on a large series of Enterobacterales since the revision of EUCAST categorization break-points in 2020. The results showed that Ceftolozane-tazobactam (C/T) had a susceptibility rate of 88% in Enterobacterales infections, with higher susceptibility in 3GC-resistant strains and lower susceptibility in CRE strains. This prospective study highlights the importance of C/T in the treatment of infections.