In vitro activity of cefiderocol against MBL-producing Gram-negative bacteria collected in North America and Europe in five consecutive annual multinational SIDERO-WT surveillance studies (2014-2019)

Abstract

Objectives: To evaluate the in vitro antibacterial activity of cefiderocol, a siderophore cephalosporin against MBL-producing clinical isolates.

Methods: MBL-producing strains were selected from clinical isolates of Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii complex collected in North America and Europe in five consecutive annual multinational SIDERO-WT surveillance studies from 2014 to 2019. MICs of cefiderocol and comparator agents were determined by the broth microdilution method according to the CLSI guideline.

Results: A total of 452 MBL-producing strains consisting of 200 Enterobacterales, 227 P. aeruginosa and 25 A. baumannii complex were identified. The highest number of MBL-producing Enterobacterales strains were detected in Greece. MBL-producing strains of both P. aeruginosa and A. baumannii complex were isolated most frequently in Russia. For Enterobacterales, 91.5% or 67.5% of MBL-producing strains had cefiderocol MIC values ≤4 mg/L (CLSI susceptibility breakpoint) or ≤2 mg/L (EUCAST susceptibility breakpoint), respectively. All MIC values of cefiderocol for MBL-producing P. aeruginosa strains were ≤4 mg/L (CLSI susceptibility breakpoint), and 97.4% of them had cefiderocol MIC values ≤2 mg/L (EUCAST susceptibility breakpoint). For A. baumannii complex, 60.0% or 44.0% of MBL-producing strains had cefiderocol MIC values ≤4 mg/L (CLSI susceptibility breakpoint) or ≤2 mg/L (EUCAST pharmacokinetic-pharmacodynamic susceptibility breakpoint), respectively. Against all types of MBL-producing strains, MIC distribution curves of cefiderocol were located in the lowest numerical values, compared with other β-lactams and β-lactam/β-lactamase inhibitor combinations tested and ciprofloxacin.

Conclusions: Although the types of MBL-producing strains isolated by country varied, cefiderocol showed potent in vitro activity against all types of MBL-producing Gram-negative bacteria regardless of the bacterial species.