Clinical drug investigation
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Cefiderocol (Fetroja®) is a siderophore cephalosporin and has demonstrated potent activity against extended-spectrum beta-lactamases producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and nonfermenting Gram-negative bacilli, including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii, Burkholderia cepacia, and Klebsiella pneumoniae. However, cefiderocol has limited activity against Gram-positive bacteria and anaerobes like Bacterodies fragilis. In the APEKS-cUTI study, 183 (73%) of 252 patients in the cefiderocol group versus 65 (55%) of 119 patients in the imipenem-cilastatin group achieved the composite outcome of clinical and microbiological eradication of Gram-negative bacteria (treatment difference of 18.58%; 95% CI 8.23-28.92, p = 0.0004) in complicated urinary tract infections (cUTIs). ⋯ The most common adverse events with cefiderocol were gastrointestinal symptoms such as diarrhea, constipation, nausea, vomiting, or upper abdominal pain. Two phase III clinical trials, the CREDIBLE-CR study and the APEKS-NP study, investigated the efficacy and safety of cefiderocol for the treatment of pneumonia or cUTI, and both studies showed higher all-cause mortality associated with cefiderocol. Therefore, the use of cefiderocol should be limited only to the treatment of cUTIs from Gram-negative bacteria, especially in patients who have limited or no alternative treatment options.