Abstract
Background
Ceftolozane–tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. The combination was cleared by FDA and EMA and is approved in the United States and over 60 countries worldwide. Using clinical isolates collected in the United States and Canada as part of the global SMART surveillance program, we compared the activity of C/T and ceftazidime–avibactam (CAZ/AVI) against P. aeruginosa isolates and subsets nonsusceptible (NS) to selected antimicrobial agents.
Methods
In 2018, 31 clinical laboratories from United States and Canada collected up to 250 consecutive, aerobic or facultatively anaerobic, Gram-negative pathogens (GNP) from blood, intra-abdominal, urinary, and lower respiratory tract infections. A total of 6,178 GNP were collected, of which 1,138 (18.4%) were P. aeruginosa. MICs were determined using CLSI broth microdilution and interpreted with CLSI 2019 breakpoints.
Results
The MIC distributions of C/T and CAZ/AVI against 1,138 P. aeruginosa are shown below. The modal MIC value for C/T was ≥2 doubling dilutions lower than that for CAZ/AVI, and it was ≥3 dilutions lower than the C/T CLSI susceptible breakpoint, whereas the modal MIC value for CAZ/AVI was 2 dilutions lower than its susceptible breakpoint. Among all P. aeruginosa isolates, percentages of susceptibility were 96.0% (C/T), 93.8% (CAZ/AVI), 76.6% (CAZ and cefepime), 67.0% (imipenem [IMI]), 74.0% (meropenem [MEM]), 71.5% (piperacillin–tazobactam [TZP]), and 64.9% (aztreonam). Among subsets of nonsusceptible isolates, susceptibilities to C/T and CAZ/AVI were 83.5% and 74.4%, respectively (CAZ-NS subset, n = 266), 91.0% and 85.1% (IMI-NS, n = 376), 87.5% and 80.1% (MEM-NS, n = 296), 87.0% and 79.6% (TZP-NS, n = 324), and 72.4% and 57.8% among isolates nonsusceptible to all tested β-lactams (n = 116).
Conclusion
The activity of C/T exceeded that of CAZ/AVI and other tested comparators against a recent collection of clinical isolates of P. aeruginosa, including subsets of isolates nonsusceptible to other β-lactams. Susceptibilities to C/T were 6–14 percentage points higher than observed for CAZ/AVI among β-lactam-NS subsets. C/T promises to be an important treatment option for patients with antimicrobial-resistant P. aeruginosa infections.
Disclosures
All authors: No reported disclosures.
Haemophilus influenzae and Moraxella catarrhalis from Patients with Community-Acquired Respiratory Tract Infections: Antimicrobial Susceptibility Patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997)
