In vitro activities of ceftazidime–avibactam, ceftolozane–tazobactam, meropenem–vaborbactam and other comparators against Pseudomonas aeruginosa isolates with discrepant resistance to carbapenems: Data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program, 2012–2021

Abstract

In this study, we aimed to investigate the in vitro susceptibility and β-lactamase-encoding genes of Pseudomonas aeruginosa isolates with discrepant resistance to various carbapenems. We obtained data on P. aeruginosa isolates from the Antimicrobial Testing Leadership and Surveillance program from 2012 to 2021. Minimum inhibitory concentrations of P. aeruginosa isolates were determined using the broth microdilution method. β-lactamase-encoding genes were identified using multiplex polymerase chain reaction assays. Among the P. aeruginosa isolates tested, the percentages of isolates resistant to imipenem, meropenem, and doripenem were 26.9% (14,447/53,617), 20.5 (14,098/68,897), and 17.5% (3,660/20,946), respectively. Imipenem-resistant P. aeruginosa isolates were more susceptible to all tested antimicrobial agents (except colistin) than the meropenem- or doripenem-resistant P. aeruginosa isolates. Carbapenemase genes were detected in 14.3% (2,020/14,098) of meropenem-resistant P. aeruginosa isolates. Imipenem-resistant meropenem-susceptible P. aeruginosa isolates had higher susceptibility profiles, fewer carbapenemase genes (0.3% [5/1,858] vs. 4.1% [10/242]; p < 0.05), and a lower risk of being classified as multidrug-resistant than the imipenem-susceptible meropenem-resistant isolates (16.1% [299/1,858] vs. .73.6% [178/242]; p < 0.05). Among all β-lactam combination agents, ceftazidime-avibactam and ceftolozane-tazobactam had higher susceptibility rates than meropenem-vaborbactam for meropenem-resistant P. aeruginosa (61.8% and 55.5% vs. 30.2%; p<0.05). In conclusion, discrepancy in the resistance of different P. aeruginosa isolates to various carbapenems suggests their different underlying resistance mechanisms. These findings can be useful for effective resistance trend monitoring and accurate antimicrobial treatment in the future.