Abstract
The global public health crisis of multidrug-resistant Gram-negative organisms underscores the need for antibiotics with novel bacterial targets. Cefiderocol, the first siderophore-conjugated antibiotic to progress beyond phase 1 human trials, was designed to overcome challenges presented by common carbapenem-resistance mechanisms. The drug enters bacterial cells using active iron transporters (ie, a Trojan horse), overcoming drug resistance from porin channel mutations and upregulated efflux pumps; it also has intrinsic stability from hydrolysis by carbapenemases. By contrast with other novel agents, cefiderocol is active against a variety of drug-resistant pathogens, including both serine and metallo-β-lactamase (MBL) carbapenemases, as well as problematic non-fermenting Gram-negative organisms, such as Pseudomonas aeruginosa, Acinetobacter baumannii complex, and Stenotrophomonas maltophilia. In The Lancet Infectious Diseases, the APEKS-NP study by Richard Wunderink and colleagues 1 Wunderink RG Matsunaga Y Ariyasu M et al. Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2020; (published online Oct 12.)https://doi.org/10.1016/S1473-3099(20)30731-3 Summary Full Text Full Text PDF Scopus (87) Google Scholar and the CREDIBLE-CR study by Matteo Bassetti and colleagues 2 Bassetti M Echols R Matsunaga Y et al. Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial. Lancet Infect Dis. 2020; (published online Oct 12.)https://doi.org/10.1016/S1473-3099(20)30796-9 Summary Full Text Full Text PDF PubMed Scopus (117) Google Scholar offer insights into the role of cefiderocol for the treatment of challenging Gram-negative infections. Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): a randomised, double-blind, phase 3, non-inferiority trialCefiderocol was non-inferior to high-dose, extended-infusion meropenem in terms of all-cause mortality on day 14 in patients with Gram-negative nosocomial pneumonia, with similar tolerability. The results suggest that cefiderocol is a potential option for the treatment of patients with nosocomial pneumonia, including those caused by multidrug-resistant Gram-negative bacteria. Full-Text PDF Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trialCefiderocol had similar clinical and microbiological efficacy to best available therapy in this heterogeneous patient population with infections caused by carbapenem-resistant Gram-negative bacteria. Numerically more deaths occurred in the cefiderocol group, primarily in the patient subset with Acinetobacter spp infections. Collectively, the findings from this study support cefiderocol as an option for the treatment of carbapenem-resistant infections in patients with limited treatment options. Full-Text PDF
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