Real-world Performance of Susceptibility Testing for Ceftolozane/Tazobactam Against Non-Carbapenemase-Producing Carbapenem-Resistant Pseudomonas aeruginosa

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2021

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Article

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Abstract

Ceftolozane/tazbactam (C/T) is a potent anti-pseudomonal agent that has clinical utility against infections caused by non-carbapenemase producing carbapenem-resistant P. aeruginosa (non-CP-CR-PA). Accurate, precise and reliable antimicrobial susceptibility testing (AST) is crucial to guide clinical decisions. However, studies assessing the performance of different AST methods against non-CP-CR-PA- (the main clinical niche for C/T), are lacking. Here, we evaluated performance of gradient strips (Etest and MIC test strip (MTS), and disk diffusion (DD) using CLSI breakpoints. Additionally, we assessed the performance of DD using EUCAST breakpoints. For all susceptibility tests, we used a collection of 97 non-CP-CR-PA clinical isolates recovered from 11 Chilean hospitals. Both gradient strips and DD had acceptable performance when using CLSI breakpoints, yielding a categorical agreement (CA) of >90% and 92%, respectively. In contrast, DD using EUCAST breakpoints performed sub-optimally (CA 81%). MTS yielded a higher essential agreement (EA, >90%) than Etest (84%). Importantly, the performance of all methods varied significantly when the isolates were stratified by their degree of susceptibility to other anti-pseudomonal β-lactams. All methods had 100% CA when testing isolates that were pan-susceptible to all β-lactams (Pan-β-S). However, the CA markedly decreased when testing isolates resistant to all β-lactams (Pan-β-R). Indeed, the CA was 81% for Etest (6 errors), 78% for MTS (7 errors) and 78% and 56% for DD when using CLSI (7 errors) or EUCAST breakpoints (14 errors), respectively. Our results suggest that all manual AST methods have strikingly decreased performance in the context of Pan-β-R P. aeruginosa with potentially major clinical implications.

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Citation

Rivas L, Alcalde-Rico M, Martínez JR, Moreno V, Rojas P, Wozniak A, García P, Olivares J, Miller WR, Arias CA, Khan A, Munita JM. Real-world Performance of Susceptibility Testing for Ceftolozane/Tazobactam Against Non-Carbapenemase-Producing Carbapenem-Resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2021 Nov 15:AAC0165721. doi: 10.1128/AAC.01657-21

Keywords

Anti-Bacterial Agents / pharmacology, Bacteriological Techniques / standards, Indicator Dilution Techniques / standards, Tazobactam / pharmacology, Ceftolozane / pharmacology, Pseudomonas aeruginosa / drug effects

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