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

The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576 Pseudomonas aeruginosa and 2,362 Enterobacteriaceae isolates 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 to 85.1% of isolates nonsusceptible to antipseudomonal beta-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 those of other beta-lactams evaluated against P. aeruginosa groups across all U.S. census divisions. Ceftolozane-tazobactam was active against 90.6% of the Enterobacteriaceae, being less active than only meropenem (95.6% susceptible) among the beta-lactams evaluated. Against 145 Escherichia coli and Klebsiella pneumoniae isolates carrying extended-spectrum-beta-lactamase (ESBL)-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) genes 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 beta-lactams displayed limited activity against bla(KPC)-carrying isolates. Ceftolozane-tazobactam was the most active beta-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 and carrying ESBL genes.