Antimicrobial Activity of Ceftazidime-Avibactam,Ceftolozane-Tazobactam and Comparators Tested Against Pseudomonas aeruginosa and Klebsiella pneumoniae Isolates from United States Medical Centers in 2016–2018

Abstract

Very few antimicrobial agents remain active against Pseudomonas aeruginosa and Klebsiella pneumoniae in some geographic regions. We evaluated the in vitro activity of ceftazidime–avibactam, ceftolozane–tazobactam, and comparator agents against 6,210 P. aeruginosa and 6,041 K. pneumoniae isolates consecutively collected from 85 U.S. medical centers across 37 states in 2016–2018. Antimicrobial susceptibility was determined by reference broth microdilution method. K. pneumoniae isolates found to have elevated MICs for broad-spectrum cephalosporins were submitted to whole-genome sequencing analysis to detect resistance genes. Ceftazidime–avibactam (97.1% susceptible [S]) and ceftolozane–tazobactam (97.0%S) were the most active compounds against P. aeruginosa and retained activity against meropenem-nonsusceptible (88.5–89.0%S), piperacillin–tazobactam-nonsusceptible (86.6–87.0%S), and other resistant subsets of isolates. The most active agents against K. pneumoniae per CLSI criteria were ceftazidime–avibactam (>99.9%S), amikacin (98.4%S), and meropenem (97.1%S). Ceftolozane–tazobactam was active against 95.3% of K. pneumoniae but showed limited activity against extended-spectrum β-lactamase and carbapenemase producers (82.9% and 0.0%S, respectively).