Ceftolozane-Tazobactam Activity Against Clinical Isolates of Pseudomonas aeruginosa from ICU Patients with Pneumonia: United States, 2015-2018.

OBJECTIVES To report on the activity of ceftolozane-tazobactam and comparators against P. aeruginosa isolates collected from hospitalized patients with pneumonia in US intensive care units between 2015 through 2018. Activity against all P. aeruginosa and common resistant phenotypes are described to better inform decision-making and support antimicrobial stewardship efforts. METHODS A total of 781 P. aeruginosa isolates collected from 28 US hospitals. These isolates were tested for susceptibility to ceftolozane-tazobactam, and comparators by CLSI broth microdilution methodology using CLSI (2020) breakpoints. Phenotypes analyzed included piperacillin-tazobactam-NS, cefepime-NS, ceftazidime-NS, meropenem-NS, and difficult-to-treat resistance (DTR). RESULTS Ceftolozane-tazobactam was the most potent agent tested (MIC50//90, 0.5/2 mg/L, 97.2% S). Traditional first line antipseudomonal β-lactam antibiotics (piperacillin-tazobactam, cefepime, and ceftazidime) demonstrated < 33% susceptibility when NS to one agent was present. Although escalation of therapy to meropenem is commonly employed clinically, meropenem susceptibility ranged from 33.6% to 44.9% if P. aeruginosa was NS to any traditional first line antipseudomonal β-lactam agent. Conversely, ceftolozane-tazobactam remained active against isolates that were NS to other agents, inhibiting 88.4% of isolates NS to piperacillin-tazobactam, 85.0% of isolates NS to cefepime and ceftazidime, and 90.3% of isolates NS to meropenem. Ceftolozane-tazobactam also maintained activity against 73.0% of DTR isolates. CONCLUSIONS Ceftolozane-tazobactam maintains high activity against P. aeruginosa isolated from hospitalized patients with pneumonia in US ICUs, including having the greatest activity against isolates NS to one or more antipseudomonal β-lactams and DTR isolates.