Update on the comparative in vitro activity of cefiderocol and four β-lactam-β-lactamase-inhibitor combinations against clinically important Gram-negative pathogens.

OBJECTIVES

Antimicrobial resistance is considered one of the most dangerous threats to public health globally. In the last decade, several antimicrobial agents were developed for the treatment of infections with multidrug-resistant Gram-negative bacteria, especially carbapenem-resistant isolates. The aim of this study was to investigate the in vitro activity of the siderophore cephalosporin cefiderocol (FDC) and four comparator beta-lactam-beta-lactamase-inhibitor combinations (ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam and meropenem/vaborbactam) against 401 clinical isolates of Gram-negative pathogens collected in Germany between 2019 and 2020.

METHODS

Genetic determinants of resistance were investigated by PCR and/or whole-genome sequencing. Furthermore, the ComASP test kit for cefiderocol minimum-inhibitory concentration (MIC) determination was compared to the EUCAST reference method broth microdilution.

RESULTS

The cefiderocol resistance rate of Pseudomonas aeruginosa was 1.5% while resistance to the comparator agents ranged from 19.7% to 40.9%. Among both Acinetobacter baumannii and Stenotrophomonas maltophilia isolates the MIC50 value of cefiderocol was six or more log2 steps lower than the ones of the comparator agents. Seven isolates (three Escherichia coli, one Klebsiella pneumoniae, one P. aeruginosa and two A. baumannii) revealed cefiderocol MICs > 2 mg/L. While different beta-lactamase genes were detected in these isolates, they were most probably not solely responsible for cefiderocol resistance. MICs produced by ComASP test kits were comparable to the results of broth microdilution in E. coli, K. pneumoniae, P. aeruginosa and S. maltophilia (categorical agreement > 95%; essential agreement > 91%).

CONCLUSIONS

Overall, cefiderocol activity against P. aeruginosa, A. baumannii and S. maltophilia was higher compared to the other agents tested.