Activity of cefepime/zidebactam (WCK 5222) against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii endemic to New York City medical centres

Background The combination of cefepime and zidebactam (WCK5222), a novel beta-lactam enhancer, has demonstrated activity against a wide variety of Gram-negative pathogens and is currently under clinical evaluation. Objectives To examine the activity of cefepime/zidebactam against: (i) a contemporary collection of Gram-negative isolates from New York City; (ii) a collection of carbapenem-resistant clinical isolates; and (iii) a collection of isolates with characterized resistance mechanisms. Methods Susceptibility tests were performed using broth microdilution for cefepime, zidebactam and cefepime/zidebactam (1:1). Results More than 99% of a contemporary collection of Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. had cefepime/zidebactam MICs <= 2mg/L, the susceptibility breakpoint for cefepime. For K. pneumoniae, the acquisition of bla(KPC) resulted in increased MICs, although MICs remained <= 2mg/L for 90% of KPC-possessing isolates. Overall for Pseudomonas aeruginosa, 98% of isolates had MICs <= 8mg/L and MICs were affected by increased expression of ampC. For carbapenem-resistant P. aeruginosa, 78% of isolates had cefepime/zidebactam MICs <= 8mg/L. The activity of cefepime/zidebactam against Acinetobacter baumannii was lower, with 85% of all isolates and 34% of carbapenem-resistant isolates with MICs <= 8mg/L (cefepime interpretative criteria). Conclusions Cefepime/zidebactam demonstrated excellent activity against Enterobacteriaceae and P. aeruginosa, although activity was reduced in carbapenem-non-susceptible isolates. The activity against A. baumannii was reduced and studies examining the therapeutic efficacy in strains with high cefepime/zidebactam MICs are warranted.