Antimicrobial Activity of Ceftolozane-Tazobactam Tested against Enterobacteriaceae and Pseudomonas aeruginosa with Various Resistance Patterns Isolated in U.S. Hospitals (2011-2012)

Abstract

Ceftolozane/tazobactam, a novel antimicrobial agent with activity against Pseudomonas aeruginosa (including drug-resistant strains) and other common Gram-negative pathogens (including most extended-spectrum-β-lactamase [ESBL]-producing Enterobacteriaceae strains), and comparator agents were susceptibility tested by a reference broth microdilution method against 7,071 Enterobacteriaceae and 1,971 P. aeruginosa isolates. Isolates were collected consecutively from patients in 32 medical centers across the United States during 2011 to 2012. Overall, 15.7% and 8.9% of P. aeruginosa isolates were classified as multidrug resistant (MDR) and extensively drug resistant (XDR), and 8.4% and 1.2% of Enterobacteriaceae were classified as MDR and XDR. No pandrug-resistant (PDR) Enterobacteriaceae isolates and only one PDR P. aeruginosa isolate were detected. Ceftolozane/tazobactam was the most potent (MIC 50/90 , 0.5/2 μg/ml) agent tested against P. aeruginosa and demonstrated good activity against 310 MDR strains (MIC 50/90 , 2/8 μg/ml) and 175 XDR strains (MIC 50/90 , 4/16 μg/ml). Ceftolozane/tazobactam exhibited high overall activity (MIC 50/90 , 0.25/1 μg/ml) against Enterobacteriaceae and retained activity (MIC 50/90 , 4/>32 μg/ml) against many 601 MDR strains but not against the 86 XDR strains (MIC 50 , >32 μg/ml). Ceftolozane/tazobactam was highly potent (MIC 50/90 , 0.25/0.5 μg/ml) against 2,691 Escherichia coli isolates and retained good activity against most ESBL-phenotype E. coli isolates (MIC 50/90 , 0.5/4 μg/ml), but activity was low against ESBL-phenotype Klebsiella pneumoniae isolates (MIC 50/90 , 32/>32 μg/ml), explained by the high rate (39.8%) of meropenem coresistance observed in this species phenotype. In summary, ceftolozane/tazobactam demonstrated high potency and broad-spectrum activity against many contemporary Enterobacteriaceae and P. aeruginosa isolates collected in U.S. medical centers. Importantly, ceftolozane/tazobactam retained potency against many MDR and XDR strains.