The activity of ceftolozane-tazobactam and comparator agents was evaluated against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States (US) during 2013 to 2015. Isolates included 1,576 Pseudomonas aeruginosa and 2,362 Enterobacteriaceae susceptibility tested using reference broth microdilution methods. Ceftolozane-tazobactam, cefepime, ceftazidime, meropenem, and piperacillin-tazobactam inhibited 96.3%, 84.8%, 83.5%, 80.0%, and 78.6%, respectively, of the P. aeruginosa isolates. Ceftolozane-tazobactam inhibited 77.5-85.1% of isolates nonsusceptible to antipseudomonal β-lactams and 86.6% and 71.0% of the 372 (23.6% overall) multidrug- and 155 (9.8%) extensively drug-resistant isolates tested. The activity of this combination was greater than other β-lactams evaluated against all P. aeruginosa groups across all US census divisions. Ceftolozane-tazobactam was active against 90.6% of the Enterobacteriaceae, being only less active than meropenem (95.6% susceptible) among the β-lactams evaluated. Against 145 Escherichia coli and Klebsiella pneumoniae isolates carrying extended-spectrum β-lactamase (ESBLs) encoding genes without carbapenemases, ceftolozane-tazobactam inhibited 82.8% of these isolates and was more active than cefepime and piperacillin-tazobactam (15.2% and 74.3% susceptible, respectively). ESBL genes included in this analysis were mainly blaCTX-M-15-like (89 isolates) and blaCTX-M-14-like (22), but also blaSHV (31) and blaTEM (3). Ceftolozane-tazobactam also displayed activity (84.6% susceptible) against 13 isolates harboring acquired AmpC genes. All β-lactams displayed limited activity against blaKPC-carrying isolates. Ceftolozane-tazobactam was the most active β-lactam tested against P. aeruginosa isolates from isolates that were the probable cause of pneumonia and displayed in vitro activity against Enterobacteriaceae, including isolates resistant to cephalosporins that carry ESBL genes.
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