FDA Approves Cefiderocol for cUTIs in Adults


Antibiotic with a novel penetrative mechanism.

urinary tract

The FDA has approved cefiderocol (Fetroja, Shionogi) for the treatment of complicated urinary tract infections (cUTIs) including pyelonephritis caused by susceptible Gram-negative microorganisms in patients 18 years of age and older who have limited or no other treatment option. 

Cefiderocol is an antibiotic with a novel mechanism for penetrating the cell membrane of gram-negative pathogens and acting as a siderophore, according to Shionogi’s official release. Once the molecule enters via passive diffusion through porin channels, it binds to ferric iron and is actively transported into bacterial cells through outer membrane iron transporters. This in turn allows the molecule to reach a higher concentration in the periplasmic space where it can then bind to penicillin-binding proteins and thereby disrupt cell wall synthesis in targeted bacteria. 

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According to Shionogi, cefiderocol has sown in vitro activity against bacteria that contain very problematic resistance enzymes such as ESBLs, AmpC, serine- and metal-carbapenemases. Potent in virto activity has also been recorded specifically against Acinetobacter baumanniiPseudomonas aeruginosa, Enterobacteriaceae, and Stenotrophomonas maltophilia. 

“FETROJA will fill a very important unmet medical need because of its unique method of penetrating the cell wall of Gram-negative bacteria and its ability to overcome many of the resistance mechanisms that bacteria employ against antibiotics. Today’s approval represents Shionogi’s ongoing commitment to develop medicines that help fight these life-threatening infections in patients for whom limited or no alternative treatment options exist,” said Isao Teshirogi, PhD, president and CEO at Shionogi in a statement.

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The FDA’s approval is based upon data from a multi-national, multicenter, double-blind trial evaluating the safety and efficacy of cefiderocol compared to imipenem/cilastatin (IPM/CS). Both arms reached the composite endpoint of microbiological eradication; however, the cefiderocol arm (72.6%) was higher than the IPM/CS arm (54.6%). Clinical response rates at the test of cure were similar between groups, according to the release.

Cefiderocol is contraindicated in patients with a known history of severe hypersensitivity to cefierocol and other beta-lactam antibacterial drugs, or any of the compounds in Fetroja. 

Warnings and precautions issued with the use of cefiderocol include a documented increase in all-cause mortality in patients with carabapenem-resistant gram-negative bacterial infections, Clostridioides difficile-associated diarrhea, seizures and other CNS adverse reactions, and hypersensitivity reactions.

Adverse events reported with the use of cefiderocol include diarrhea, infusion site reactions, constipation, rash, candidiasis, cough, elevations in liver tests, headache, hypokalemia, nausea, and vomiting.


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