In vitro potency of antipseudomonal β-lactams against blood and respiratory isolates of P. Aeruginosa collected from US hospitals

Abstract

Background: Challenges due to multidrug resistant (MDR) Gram-negative bacterial pathogens such as P. aeruginosa (PSA) are increasing globally. Suboptimal antimicrobial therapy of infections caused by PSA is associated with increased morbidity and mortality. As a result, antimicrobial susceptibility (%S) studies are pivotal to identifying trends in antimicrobial resistance that inform decisions regarding choice of antimicrobial therapy. This study assessed the in vitro potency of 7 antipseudomonal agents including ceftolozane/tazobactam (C/T) against PSA collected from numerous sites across the US. Methods: Multiple US hospitals provided non-duplicate respiratory and blood isolates of PSA for potency testing. MICs against PSA were determined using broth microdilution methods according to CLSI for 7 antimicrobials with antipseudomonal activity: aztreonam (ATM), cefepime (FEP), ceftazidime (CAZ), C/T, imipenem (IPM), meropenem (MEM) and piperacillin/tazobactam (TZP). %S was defined per CLSI or FDA breakpoint criteria. Results: Thirty-five hospitals geographically spread across the US provided a total of 1,209 PSA isolates. Of the antibiotics assessed, %S to C/T was the highest at 95% with an MIC50 of 0.5 mg/L and MIC90 of 2 mg/L. In comparison, other %S (MIC50/MIC90) was as follows: ATM 66% (8/32); FEP 76% (4/32); CAZ 78% (4/64); IPM 68% (2/16); MEM 74% (0.5/16); and TZP 73% (8/128). Conclusions: For this geographically diverse PSA population, C/T demonstrated the highest overall susceptibility (95%). Other antipseudomonal agents inclusive of the carbapenems displayed susceptibilities of 66-78%. In the era of escalating PSA resistance to the β-lactams, the potency of C/T may represent an important clinical option.