Global Assessment of High-Proportion Cefepime-Tazobactam's Antimicrobial Efficacy Against Gram-Negative Isolates

In the ongoing clinical development, cefepime-tazobactam (WCK 4282) is administered at a dosage of 2 g/2 g every 8 hours. The antimicrobial efficacy of this combination was assessed in 2014 through the SENTRY Surveillance Program, which gathered 7,981 isolates from 146 medical centers across 39 countries. The susceptibility testing was performed using a reference broth microdilution method with fixed tazobactam concentrations of 4 and 8 μg/ml. The majority of the isolates originated from patients with pneumonia (29.5%) and bloodstream infections (26.9%). Cefepime-tazobactam, particularly with tazobactam at 8 μg/ml, demonstrated a high inhibition rate of 96.9% against Enterobacteriaceae strains, compared to 87.9% for cefepime alone.

The effectiveness of cefepime-tazobactam was found to be similar to meropenem, which had a susceptibility rate of 96.7%, and superior to piperacillin-tazobactam, with a rate of 87.7%. In the United States, all Enterobacteriaceae species except Klebsiella pneumoniae showed over 99.0% inhibition at the ≤8/8 μg/ml concentration. Notably, the prevalence of the ESBL-screening-positive phenotype was highest among Escherichia coli isolates in China (66.3%) and K. pneumoniae isolates in Latin America (58.0%). Cefepime-tazobactam at the same concentration inhibited 98.7% of ESBL-positive E. coli strains and 71.3% of K. pneumoniae strains. In contrast, meropenem showed limited activity against ESBL-positive K. pneumoniae strains, with a susceptibility rate of 69.6%.

Furthermore, cefepime-tazobactam was found to be active against Enterobacter spp., including ceftazidime-nonsusceptible isolates, with a high inhibition rate of 96.1% at the ≤8/8 μg/ml concentration. The activity against Pseudomonas aeruginosa was also comparable to that of meropenem and piperacillin-tazobactam, with inhibition rates of 82.4% and 91.6% at the ≤8/8 and ≤16/8 μg/ml concentrations, respectively.

Overall, the study indicates that cefepime-tazobactam exhibits a high level of activity against P. aeruginosa and Enterobacteriaceae strains, including ESBL-positive E. coli strains and ceftazidime-nonsusceptible Enterobacter spp. These findings support the continued clinical development of the cefepime-tazobactam combination.