Activity of Ceftolozane-Tazobactam Tested against Pseudomonas aeruginosa and Enterobacteriaceae Isolates Collected from Respiratory Tract Specimens of Hospitalized Patients in the United States During 2013 to 2015 [PublishAheadOfPrint]

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 bla_CTX-M-15-like (89 isolates) and bla_CTX-M-14-like (22), but also bla_SHV (31) and bla_TEM (3). Ceftolozane-tazobactam also displayed activity (84.6% susceptible) against 13 isolates harboring acquired AmpC genes. All β-lactams displayed limited activity against bla_KPC-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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