In Vivo Activity of Cefiderocol Against Resistant Gram-Negative Bacteria

The activity of siderophore cephalosporin cefiderocol against carbapenem-resistant gram-negative Enterobacteriaceae was determined and published as a brief report in Antimicrobial Agents and Chemotherapy.

The investigators determined minimum inhibitory concentrations (MICs) of cefiderocol and comparators by microdilution in iron-depleted Mueller Hinton broth against characterized carbapenem-resistant Acinetobacter baumannii complex, Stenotrophomonas maltophilia, Pseudomonas aeruginosa and Enterobacteriaceae. The MICs were read as the first well in which growth was reduced (button of <1 mm or light/faint turbidity) relative to growth in a control well. A total of 1086 isolates of these gram-negative bacteria were tested.

The overall MIC₉₀ for cefiderocol against A baumannii, S maltophilia and P aeruginosa were 1, 0.25, and 0.5 mg/L, respectively. The MIC₉₀ against Enterobacteriaceae was 4 mg/L overall; activity of cefiderocol with various extended spectrum beta-lactamases and carbapenemases against Enterobacteriaceae was 1 mg/L for OXA-48-like beta-lactamase group; 2 mg/L for the KPC-3 group; and 8 mg/L for the TEM/SHV ESBL, NDM, and KPC-2 groups.

The investigators concluded that, “our findings support in vivo activity of this agent against carbapenem-resistant gram-negative non-fermenters and most carbapenem-resistant Enterobacteriaceae.” They further suggested that cefiderocol may be a valuable addition to the currently limited arsenal available for fighting infections caused by resistant gram-negative non-fermenters.

Reference

Jacobs MR, Abdelhamed AM, Good CE, et al. ARGONAUT-I: Activity of cefiderocol (S-649266), a siderophore cephalosporin, against Gram-negative bacteria including carbapenem resistant nonfermenters and Enterobacteriaceae with defined extended-spectrum β-lactamases and carbapenemases [published online October 15 2018]. Antimicrob Agents Chemother. doi:10.1128/AAC.01801-18