Objectives: To evaluate the in vitro activity of ceftolozane/tazobactam and comparator agents tested against contemporary Gram-negative bacteria. Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a well-established b-lactamase inhibitor. Methods: A total of 10532 Gram-negative organisms (2191 Pseudomonas aeruginosa and 8341 Enterobacteriaceae) were consecutively collected from 31 medical centres located in 13 European countries plus Turkey and Israel. The organisms were

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... sted for susceptibility by broth microdilution methods as described by the CLSI M07-A9 document and the results interpreted according to EUCAST as well as CLSI breakpoint criteria. Selected ceftazidime-and/or meropenem-resistant P. aeruginosa isolates were screened for the presence of b-lactamase genes by PCR. Results: P. aeruginosa exhibited high rates of multidrug-resistant (31.9%) and extensively drug-resistant (24.6%) isolates and 11.6% of isolates were susceptible only to colistin. When tested against P. aeruginosa, ceftolozane/ tazobactam (MIC 50 , 1 mg/L) was generally 4-fold more active than ceftazidime (MIC 50 , 4 mg/L) and inhibited .90% of isolates with an MIC of ≤8 mg/L in nine countries. In contrast, the highest susceptibility rates observed for ceftazidime and meropenem, respectively, were 86.0%/86.0% (UK) and 85.2%/86.1% (Ireland) (67.2%/ 67.1% overall). Ceftolozane/tazobactam (MIC 50/90 , 0.25/2 mg/L; 93.7% and 95.2% inhibited at ≤4 and ≤8 mg/L, respectively), meropenem [MIC 50/90 , ≤0.06/≤0.06 mg/L; 98.0% susceptible (EUCAST)] and tigecycline [MIC 50/90 , 0.12/1 mg/L; 94.1% susceptible (EUCAST)] were the most active compounds tested against Enterobacteriaceae. Conclusions: Ceftolozane/tazobactam was the most active b-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than currently available cephalosporins and piperacillin/tazobactam when tested against Enterobacteriaceae.