In vitro activity of cefiderocol against clinically important carbapenem non-susceptible Gram-negative bacteria from Saudi Arabia

Abstract

Cefiderocol is a novel catechol-substituted siderophore cephalosporin with broad-spectrum activity against Gram-negative pathogens. However, variation of its activity among carbapenemase producers from various regions and countries has been reported. Here, we checked the in vitro activity against Gram-negative carbapenem non-susceptible bacteria collected in Saudi Arabia. Cefiderocol MICs were determined using the iron-depleted cation-adjusted Mueller-Hinton brothand interpreted according to the Clinical and Laboratory Standards Institute guidelines. Isolates (n=288) included carbapenemase-producing Escherichia coli (n=46), Klebsiella pneumoniae (n=98), Acinetobacter baumannii (n=65), and Pseudomonas aeruginosa (n=79) clinical isolates. Cefiderocol inhibited 73.26% (211/288) of the isolates studied at concentrations of ≤ 4 mg/L. Cefiderocol inhibited all carbapenem-resistant A. baumannii isolates (65/65, 100%) producing OXA-23-like, OXA-24-like, and NDM, and nearly all P. aeruginosa isolates (75/79, 94.94%), including those producing VIM and NDM. In contrast, the carbapenemase-producing isolates from the Enterobacterales group demonstrated significantly higher MICs with only 53.06% (52/98) of K. pneumoniae and 41.3% (19/46) of E. coli isolates exhibiting MICs of ≤4 mg/L. Isolates showing elevated MICs (73/144, 50.69%) included NDM (20/29, 68.97%), NDM/OXA-48-like (34/59, 57.63%), OXA-48-like (18/52, 34.62%), and KPC (1/4, 25%) producers, thus showing no clear association with the production of serine-type or metallo-type carbapenemases. However, high cefiderocol MICs (≥ 32mg/L) were associated with isolates producing NDM, and in particular, among those coproducing the OXA-232-type enzyme. Cefiderocol had excellent activity against multi-drug resistant non-fermenting Gram-negative pathogens. Reasons behind the high cefiderocol MICs in certain Enterobacterales isolates need further investigation.