Antimicrobial Activity of High-Proportion Cefepime-Tazobactam (WCK 4282) against a Large Number of Gram-Negative Isolates Collected Worldwide in 2014

Cefepime-tazobactam (WCK 4282) is currently under clinical development for use at a dosage of 2 g/2 g every 8 h. A total of 7,981 isolates were collected from 146 medical centers (39 countries) in 2014 as a part of the SENTRY Antimicrobial Surveillance Program, and their susceptibilities to cefepime-tazobactam (with tazobactam at fixed concentrations of 4 and 8 mu g/ml) were tested by a reference broth microdilution method. Isolates were mainly from patients with pneumonia (29.5%) and bloodstream infections (26.9%). Cefepime-tazobactam (with tazobactam at a fixed concentration of 8 mu g/ml) and cefepime inhibited 96.9 and 87.9% of Enterobacteriaceae strains at <= 8 mu g/ml. The activity of cefepime-tazobactam against Enterobacteriaceae strains was comparable to that of meropenem (96.7% of isolates were susceptible) and greater than that of piperacillin-tazobactam (87.7% susceptible). All Enterobacteriaceae species from the United States except Klebsiella pneumoniae had > 99.0% of isolates inhibited by cefepime-tazobactam at <= 8/8 mu g/ml. The prevalence of the extended-spectrum beta-lactamase (ESBL)-screening-positive phenotype was the highest among Escherichia coli isolates in China (66.3%) and among K. pneumoniae isolates (58.0%) in Latin America. Cefepime-tazobactam at <= 8/8 mu g/ml inhibited 98.7 and 71.3% of ESBL-screening-positive phenotype E. coli strains and K. pneumoniae strains, respectively. Meropenem showed limited activity against ESBL-screening-positive phenotype K. pneumoniae strains (69.6% susceptible). Cefepime-tazobactam was active against Enterobacter spp. (MIC50 and MIC90, 0.06 and 0.5 mu g/ml, respectively), including ceftazidime-nonsusceptible isolates (96.1% of isolates were inhibited by cefepimetazobactam at <= 8/8 mu g/cl). The activity of cefepime-tazobactam against Pseudomonas aeruginosa (82.4 and 91.6% of isolates were inhibited by cefepime-tazobactam at <= 8/8 and <= 16/8 mu g/ml, respectively) was comparable to that of meropenem and piperacillin- tazobactam (79.2% susceptible). In summary, cefepime-tazobactam was highly active against P. aeruginosa and Enterobacteriaceae strains, including ESBLscreening-positive phenotype E. coli strains and ceftazidime-nonsusceptible Enterobacter spp. These results support the further clinical development of the cefepimetazobactam combination.