Background: The treatment of P. aeruginosa (PSA) infections is challenging due to this species innate resistance to several antimicrobial classes. Resistance to carbapenems is increasingly reported among PSA and new therapeutic options to treat these infections are needed. We evaluated the in vitro activity of ceftolozane/tazobactam (C/T) and comparators against carbapenem non-susceptible (carb-NS) PSA.
Methods: 894 carb-NS PSA clinical isolates were collected from 32 hospitals located in USA during 2012-2015 as part of the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS). Isolates were tested for susceptibility (S) to C/T (inhibitor at fixed 4 µg/ml) and comparators using CLSI broth microdilution methods.
Results: Among 3,851 PSA isolates, 894 (23.2%) were NS using the CLSI criteria to at least one of the following carbapenems: meropenem, imipenem or doripenem. Carb-NS PSA displayed low S rates for various agents tested (Table). C/T (MIC50/90, 1/4 µg/ml) inhibited 90.0% of the isolates at the current CLSI/EUCAST S breakpoints and was the most active β-lactam against these isolates. Among non-β-lactams, colistin (MIC50/90, 1/2 µg/ml; 98.9/99.7% S for CLSI/EUCAST criteria) was the most active agent, followed by amikacin. Amikacin was active against 91.7% of the isolates using CLSI interpretative criteria and 82.3% applying EUCAST breakpoints. Cefepime, ceftazidime and piperacillin-tazobactam were active against 60.4, 61.6 and 51.5% of the isolates using CLSI or EUCAST breakpoints, respectively. C/T inhibited 85.7% (517/603), 89.6% (744/830) and 87.6% (612/699) of the doripenem-, imipenem- and meropenem-NS isolates, respectively
Conclusion: PSA is a leading cause of nosocomial infections with high mortality rates and high levels of carbapenem resistance have been observed worldwide. C/T retained activity against 90.0% of the carb-NS PSA from USA hospitals and was demonstrated to be a valuable therapeutic option for these isolates.
Cubist Pharmaceuticals, Inc.:
H. S. Sader, Cubist Pharmaceuticals, Inc.: Research Contractor , Research grant
R. K. Flamm, Cubist Pharmaceuticals, Inc.: Research Contractor , Research grant