Ceftolozane-tazobactam Activity Against Drug-resistant Enterobacteriaceae and Pseudomonas Aeruginosa Causing Healthcare-associated Infections in Australia and New Zealand: Report from an Antimicrobial Surveillance Program (2013-2015)

Objectives: To evaluate the in vitro activity of ceftolozane-tazobactam and comparator agents tested against isolates of Enterobacteriaceae and Pseudomonas aeruginosa from patients in Australia and New Zealand with healthcare-associated infection.

Methods: A total of 1459 gram-negative organisms (440 P. aeruginosa and 1019 Enterobacteriaceae) were consecutively collected from 11 medical centers located in Australia and New Zealand. The organisms were tested for susceptibility by broth microdilution methods as described by the CLSI M07-A10 document and the results interpreted according to EUCAST and CLSI breakpoint criteria.

Results: Ceftolozane-tazobactam (MIC, 0.25/0.5μg/mL; 97.7/95.9% susceptible [CLSI/EUCAST]), meropenem (MIC, ≤0.06/≤0.06μg/mL; 99.8/99.9% susceptible [CLSI/EUCAST]) and amikacin (MIC, 2/4μg/mL; 99.8/99.6% susceptible [CLSI/EUCAST]) were the most active compounds tested against Enterobacteriaceae. Enterobacteriaceae isolates displayed susceptibility rates to other β-lactam agents ranging from 95.3/94.4% for cefepime, 94.1/91.4% for piperacillin-tazobactam, and 93.3/91.5% for ceftazidime using CLSI/EUCAST breakpoints. Among the Enterobacteriaceae isolates tested, 0.1% were CRE and 6.6% exhibited an ESBL non-CRE phenotype. Whereas ceftolozane-tazobactam showed good activity against ESBL non-CRE phenotype strains of Enterobacteriaceae (MIC, 0.5/2μg/mL), it lacked useful activity (MIC, >32μg/mL) against the single isolate with a CRE resistant phenotype. Ceftolozane-tazobactam was the most potent (MIC, 0.5/2μg/mL) β-lactam agent tested against P. aeruginosa isolates, inhibiting 95.7% at an MIC of ≤4μg/mL.

Conclusions: Ceftolozane-tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than currently available cephalosporins and piperacillin-tazobactam when tested against Enterobacteriaceae.