[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]
Activity of cefepime/zidebactam (WCK 5222) against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii endemic to New York City medical centres
Zeb Khan, Alejandro Iregui, David Landman, John Quale
Journal of Antimicrobial Chemotherapy, dkz294, https://doi.org/10.1093/jac/dkz294
Published: 11 July 2019
The combination of cefepime and zidebactam (WCK5222), a novel β-lactam enhancer, has demonstrated activity against a wide variety of Gram-negative pathogens and is currently under clinical evaluation.
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.
Susceptibility tests were performed using broth microdilution for cefepime, zidebactam and cefepime/zidebactam (1:1).
More than 99% of a contemporary collection of Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. had cefepime/zidebactam MICs ≤2 mg/L, the susceptibility breakpoint for cefepime. For K. pneumoniae, the acquisition of blaKPC resulted in increased MICs, although MICs remained ≤2 mg/L for 90% of KPC-possessing isolates. Overall for Pseudomonas aeruginosa, 98% of isolates had MICs ≤8 mg/L and MICs were affected by increased expression of ampC. For carbapenem-resistant P. aeruginosa, 78% of isolates had cefepime/zidebactam MICs ≤8 mg/L. The activity of cefepime/zidebactam against Acinetobacter baumannii was lower, with 85% of all isolates and 34% of carbapenem-resistant isolates with MICs ≤8 mg/L (cefepime interpretative criteria).
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.
Topic: pseudomonas aeruginosa – cefepime – enterobacter – enterobacteriaceae – new york city – acinetobacter baumannii – bacterial carbapenemase resistance blakpc gene – malnutrition-inflammation-cachexia syndrome – carbapenem resistance
Issue Section: ORIGINAL RESEARCH
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Keywords: Antibiotics; Drugs Resistance; Carbapenem; Enterobacteriaceae; Pseudomonas aeruginosa; Acinetobacter baumannii; Cefepine; Zidebactam; USA; NYC.