In vitro activity of ceftolozane/tazobactam against clinical isolates of Pseudomonas aeruginosa and Enterobacteriaceae recovered in Spanish medical centres: Results of the CENIT study

Abstract

Ceftolozane/tazobactam is a novel antimicrobial agent with activity against Pseudomonas aeruginosa, including drug-resistant strains, and other Gram-negative pathogens, including most extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. The CENIT study evaluated the in vitro activity of ceftolozane/tazobactam and comparators against clinical isolates of P. aeruginosa (n=500) and Enterobacteriaceae (n=500) collected from patients with complicated intra-abdominal, complicated urinary tract, lower respiratory tract or bloodstream infections in 10 medical centres in Spain (January-September 2013). Antimicrobial susceptibility was determined by the ISO broth microdilution method using commercial dry-form panels and results were interpreted per EUCAST and CLSI guidelines and for ceftolozane/tazobactam with FDA criteria. Ceftolozane/tazobactam and ceftolozane alone were the most potent (MIC(50/90), 0.5/4 mg/L) agents tested against all P. aeruginosa isolates. This advantage was maintained regardless of resistance phenotype, even against isolates resistant to multiple antibiotics. Ceftolozane/tazobactam demonstrated excellent overall activity (MIC50/90, 0.25/0.5 mg/L) against all 250 Escherichia coli isolates, including isolates displaying a wild-type (MIC(90), 0.25/0.25 mg/L) or ESBL (MIC(50/90), 0.5/1mg/L) phenotype, and good activity against isolates displaying an AmpC-like phenotype (MIC range 0.25-4 mg/L). Ceftolozane/tazobactam demonstrated good overall activity (MIC(50/90), 0.25/4 mg/L) against all 104 Klebsiella spp. isolates, although activity was lower against those with an ESBL phenotype (MIC(50/90), 4/16 mg/L), and was inactive against the carbapenemase-producing isolates (MIC≥64 mg/L). Ceftolozane/tazobactam demonstrated excellent in vitro activity against most of the P. aeruginosa and Enterobacteriaceae clinical isolates obtained from medical centres in Spain, supporting the potential value of ceftolozane/tazobactam in treating infections due to these pathogens.

Keywords: Antimicrobial resistance; Ceftolozane/tazobactam; Gram-negative; Surveillance.