In-vitro activity of cefiderocol, cefepime/zidebactam, cefepime/enmetazobactam, omadacycline, eravacycline and other comparative agents against carbapenem-nonsusceptible Enterobacterales: results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) in 2017-2020

Abstract

This study examined the susceptibility of carbapenem-nonsusceptible Enterobacterales (CNSE) to cefiderocol, cefepime/zidebactam, cefepime/enmetazobactam, omadacycline, eravacycline and other comparative agents. Non-duplicate Enterobacterales isolates from 16 Taiwanese hospitals were evaluated. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibility results were interpreted based on relevant guidelines. In total, 201 CNSE isolates were investigated, including 26 Escherichia coli isolates and 175 Klebsiella pneumoniae isolates. Carbapenemase genes were detected in 15.4% (n=4) of E. coli isolates and 47.4% (n=83) of K. pneumoniae isolates, with the most common being bla_KPC (79.3%, 69/87), followed by bla_OXA-48-like (13.8%, 12/87). Cefiderocol was the most active agent against CNSE; only 3.8% (n=1) of E. coli isolates and 4.6% (n=8) of K. pneumoniae isolates were not susceptible to cefiderocol. Among the carbapenem-resistant E. coli and K. pneumoniae isolates, 88.5% (n=23) and 93.7% (n=164), respectively, were susceptible to ceftazidime/avibactam. For cefepime/zidebactam, 23 (88.5%) E. coli isolates and 155 (88.6%) K. pneumoniae isolates had MICs ≤2/2 mg/L. For cefepime/enmetazobactam, 22 (84.6%) E. coli isolates and 85 (48.6%) K. pneumoniae isolates had MICs ≤2/8 mg/L. The higher MICs of K. pneumoniae against cefepime/enmetazobactam were due to only one (1.5%) of the 67 bla_KPC-carrying isolates being susceptible. MICs of omadacycline were significantly higher than those of eravacycline and tigecycline. In summary, cefiderocol, ceftazidime/avibactam and cefepime/zidebactam were more effective against carbapenem-nonsusceptible E. coli and K. pneumoniae than other drugs, highlighting their potential as valuable therapeutics.

Keywords: Cefiderocol; Eravacycline; Escherichia coli; Klebsiella pneumoniae; Klebsiella pneumoniae carbapenemase; Omadacycline; β-lactamase inhibitor combinations.