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

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

Edité par CCSD ; Elsevier -

International audience. 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 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 3rd generation cephalosporins (3GC) (ESBL production or different levels of AmpC overexpression) (n=213) and carbapenem resistant Enterobacterales (CRE) (n=259) including 170 carbapenemase producers (CPE). Then, 1,632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by Etest® (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 1,632 clinical isolates demonstrated 99 % of categorization agreement between MIC to C/T determined by Etest® compared to BMD (reference) and only 74% of essential agreement.Conclusion: Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers and ESBL-producing E. coli but is less active against ESBL-producing K. pneumoniae and CRE. Etest® led to an underestimation of the MICs in comparison to BMD.

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