Activity of ceftolozane-tazobactam and comparators against Pseudomonas aeruginosa from patients in different risk strata - SMART United States 2016-2017.

Objectives: Infections caused by Pseudomonas aeruginosa are often difficult to treat. Knowledge of the risk of infection with resistant P. aeruginosa would allow more discriminatory prescribing of broad-spectrum antimicrobials. Using clinical isolates collected as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART), we examined the activity of commonly used β-lactams, levofloxacin, and ceftolozane-tazobactam (C/T), an antipseudomonal cephalosporin/β-lactamase inhibitor approved in the United States and over 60 countries worldwide, against P. aeruginosa isolates from patients in different risk strata.

Methods: In 2016-2017, 25 hospitals in the US each collected up to 250 consecutive gram-negative bacilli per year from respiratory tract (RTI), intraabdominal (IAI), and urinary tract (UTI) infections. MICs of 9,964 isolates (including 1,887 P. aeruginosa) were determined using CLSI broth microdilution and interpreted with CLSI breakpoints.

Results: Susceptibility of all P. aeruginosa isolates combined was 94.7% to C/T and 76.8%, 77.0%, 70.2%, and 69.0% to ceftazidime, meropenem, piperacillin-tazobactam, and levofloxacin, respectively. Susceptibility to the β-lactam comparators was 8-11 percentage points lower among ICU than non-ICU isolates, 7-11 points lower in isolates collected ≥48h than <48h post-admission, 1-5 points lower in patients <65 years of age than older patients, and 3-12 points lower in RTI than IAI and UTI isolates. C/T maintained activity against >90% of P. aeruginosa isolates in all risk strata and against 75-88% of isolates nonsusceptible to ceftazidime, meropenem, or piperacillin-tazobactam.

Conclusions: C/T represents a promising new treatment option even in strata in which the risk of infection with β-lactam-nonsusceptible P. aeruginosa appeared higher.