In vitro activity of ceftazidime/avibactam against urinary isolates from patients in a Phase 3 clinical trial programme for the treatment of complicated urinary tract infections

Abstract

Objectives: To evaluate the in vitro activity of ceftazidime/avibactam relative to comparator agents against Gram-negative isolates from a Phase 3 clinical trial programme for complicated urinary tract infections (RECAPTURE). Methods: The in vitro activity of ceftazidime/avibactam was evaluated against 840 Gram-negative pathogens isolated at baseline from 1033 randomized patients in two pivotal Phase 3 clinical trials for the treatment of complicated urinary tract infections. The trials were conducted in 160 institutions from 25 countries worldwide. Susceptibility testing was performed by broth microdilution at a central laboratory according to CLSI methodologies. Results: Overall, ceftazidime/avibactam showed significant activity against the Enterobacteriaceae and Pseudomonas aeruginosa with MIC90 values of 0.5 and 8mg/L, respectively. Against the most common Enterobacteriaceae, MIC90 values were 0.25mg/L for Escherichia coli, 1mg/L for Klebsiella pneumoniae, 0.06mg/L for Proteus mirabilis and 2mg/L for Enterobacter cloacae. The ceftazidime/avibactam MIC90 for 154 ceftazidimenon- susceptible isolates of Enterobacteriaceae was 1mg/L and the ceftazidime/avibactam MIC90 for 15 nonsusceptible isolates of P. aeruginosa was 64mg/L. There was a significant reduction in the ceftazidime/avibactam MIC relative to ceftazidimealone formost of the Enterobacteriaceae isolates. Conclusions: The ceftazidime/avibactam in vitro activity against these clinical urinary tract isolates demonstrates the potential utility of the drug in complicated urinary tract infections.