Antimicrobial activity of cefepime/zidebactam (WCK 5222), a β-lactam/β-lactam enhancer combination, against clinical isolates of Gram-negative bacteria collected worldwide (2018-19)

Background Zidebactam, a bicyclo-acyl hydrazide beta-lactam 'enhancer' antibiotic, in combination with cefepime (WCK 5222) is under clinical development for the treatment of resistant Gram-negative infections. Objectives To evaluate the in vitro activity of cefepime/zidebactam and comparators against 24 220 Gram-negative bacteria. Methods Organisms were consecutively collected in 2018-19 from 137 medical centres located in the USA (n = 9140), Western Europe (W-EU; n = 5929), Eastern Europe (E-EU; n = 3036), the Asia-Pacific region (APAC; n = 3791) and Latin America (LATAM; n = 2324). The isolates were susceptibility tested using the broth microdilution method as part of the SENTRY Program. Cefepime/zidebactam was tested at a 1:1 ratio. Results Cefepime/zidebactam was highly active against Enterobacterales (MIC50/90 0.03/0.25 mg/L; 99.9% inhibited at <= 8 mg/L) and retained potent activity against carbapenem-resistant Enterobacterales (CRE) isolates (97.8% inhibited at <= 8 mg/L). CRE rates varied widely from 1.1% in the USA to 1.9% in W-EU, 3.6% in APAC and 14.6% in E-EU (3.9% overall). The most common carbapenemase genes observed overall were bla(KPC) (37.6% of CRE), bla(OXA-48)-like (30.0%) and bla(NDM) (23.8%). Resistance to ceftazidime/avibactam among CRE was elevated in APAC (64.8%), E-EU (25.5%) and LATAM (20.7%). Against Pseudomonas aeruginosa, cefepime/zidebactam inhibited 99.2% of isolates at <= 8 mg/L and susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam was lowest in E-EU (83.9% and 82.0%, respectively). Cefepime/zidebactam exhibited good activity against Stenotrophomonas maltophilia (80.0% inhibited at <= 8 mg/L) and Burkholderia cepacia (89.4% inhibited at <= 8 mg/L). Conclusions Cefepime/zidebactam demonstrated potent in vitro activity against a large worldwide collection of contemporary clinical isolates of Gram-negative bacteria.

Automated summary

The study evaluated the activity of cefepime/zidebactam against Gram-negative bacteria, showing good efficacy against Enterobacterales and carbapenem-resistant isolates. It demonstrated potential antibiotic effects on a global scale.