Abstract
Ceftolozane/tazbactam (C/T) is a potent anti-pseudomonal agent that has clinical utility against infections caused by non-carbapenemase, producing-carbapenem-resistant Pseudomonas 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 suboptimally (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 (six errors), 78% for MTS (seven errors), and 78% and 56% for DD when using CLSI (seven 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.
Original language | English (US) |
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Article number | e01657-21 |
Pages (from-to) | e0165721 |
Journal | Antimicrobial Agents and Chemotherapy |
Volume | 66 |
Issue number | 1 |
DOIs | |
State | Published - Jan 18 2022 |
Keywords
- Antibiotic resistance
- Antimicrobial activity
- Beta-lactams
- Bloodstream infections
- Carbapenem-resistant P. aeruginosa
- Ceftolozane/tazobactam
- Gram-negative bacteria
- Infectious disease
- Multidrug resistance
- Non-carbapenemase-producing
- Pseudomonas
- Pseudomonas aeruginosa
- Susceptibility testing
- Carbapenems/pharmacology
- Humans
- Anti-Bacterial Agents/pharmacology
- Microbial Sensitivity Tests
- Cephalosporins/pharmacology
- Tazobactam/pharmacology
- Pseudomonas Infections/drug therapy
ASJC Scopus subject areas
- Pharmacology (medical)
- Infectious Diseases
- Pharmacology