In Vitro Activity of Cefiderocol Against a Broad Range of Clinically Important Gram-negative Bacteria

Abstract

Carbapenem-resistant gram-negative bacteria including Enterobacteriaceae as well as nonfermenters, such as Pseudomonas aeruginosa and Acinetobacter baumannii, have emerged as significant global clinical threats. Although new agents have recently been approved, none are active across the entire range of resistance mechanisms presented by carbapenem-resistant gram-negative bacteria. Cefiderocol, a novel siderophore cephalosporin, has been shown in large surveillance programs and independent in vitro studies to be highly active against all key gram-negative causative pathogens isolated from patients with hospital-acquired or ventilator-associated pneumonia, bloodstream infections, or complicated urinary tract infections. The improved structure, the novel mode of entry into bacteria, and its stability against carbapenemases enables cefiderocol to exhibit high potency against isolates that produce carbapenemases of all classes or are resistant due to porin channel mutations and/or efflux pump overexpression. Resistance to cefiderocol is uncommon and appears to be multifactorial.

Keywords: Stenotrophomonas maltophilia; carbapenem-resistant Acinetobacter; carbapenem-resistant Enterobacteriaceae; carbapenem-resistant Pseudomonas; cefiderocol.

Figure 1.

Minimum inhibitory concentration distribution of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia combined from 3 annual consecutive SIDERO-WT studies. Adapted from [20, 21, 24–40]. Abbreviation: MIC, minimum inhibitory concentration.

Figure 2.

Distribution of carbapenemases produced by carbapenem-resistant Enterobacteriaceae, from the SIDERO-CR study between regions (A) and countries (B). Adapted from [38, 44]. Abbreviations: GES, Guiana extended-spectrum β-lactamase; IMP, imipenemase metallo-β-lactamase; KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase; OXA, oxacillin carbapenemase; VIM, Verona integron-encoded metallo-β-lactamase.

Figure 3.

In vitro activity of cefiderocol against various carbapenemase producers from the SIDERO-CR study. Adapted from [23, 44]. Abbreviations: GES, Guiana extended-spectrum β-lactamase; IMP, imipenemase metallo-β-lactamase; KPC, Klebsiella pneumoniae carbapenemase; MIC, minimum inhibitory concentration; NDM, New Delhi metallo-β-lactamase; OXA, oxacillin carbapenemase; VIM, Verona integron-encoded metallo-β-lactamase.