The US Food and Drug Administration (FDA) has approved the antibacterial drug cefiderocol (Fetroja) for complicated urinary tract infections (cUTI), including kidney infections, caused by susceptible Gram-negative microorganisms in patients age 18 years or older with few or no alternative treatment options.
Cefiderocol is a cephalosporin antibiotic with a novel mechanism for penetrating the outer cell membrane of Gram-negative pathogens by acting as a siderophore, the company noted in a news release announcing approval.
The approval follows a 14 to 2 vote last month in favor of approval by the FDA’s Antimicrobial Drugs Advisory Committee, as reported by Medscape Medical News.
“I think the data from the cUTI study were straightforward and demonstrated meaningful activity,” committee chairperson Lindsey R. Baden, MD, director of clinical research, Division of Infectious Diseases, Brigham and Women’s Hospital, and associate professor, Harvard Medical School, Boston, Massachusetts, said at the meeting.
In an FDA statement announcing the approval, John Farley, MD, MPH, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, said addressing the threat of antimicrobial-resistant infections, like cUTIs, is a “key global challenge the FDA faces as a public health agency. This approval represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections.”
The safety and effectiveness of cefiderocol was demonstrated in a study of 448 patients with cUTIs, with 72.6% of patients treated with cefiderocol experiencing resolution of symptoms and eradication of the bacteria roughly 7 days after completing treatment, compared with 54.6% in patients who received an alternative antibiotic. The clinical response rates were similar between the two treatment groups.
The FDA will require a warning on the label because a higher all-cause mortality rate was observed in cefiderocol-treated patients compared with those who were treated with other antibiotics in a trial involving critically ill patients with multidrug-resistant, Gram-negative bacterial infections.
The FDA says the cause of the increase in mortality has not been established. Some of the deaths were a result of worsening infection, complications of infection, or underlying comorbidities.
The FDA also notes that the higher all-cause mortality rate was observed in patients treated for nosocomial pneumonia, bloodstream infections, or sepsis. The safety and efficacy of cefiderocol has not been established for the treatment of these types of infections.
The most common adverse reactions observed with cefiderocol include diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion site reactions, candidiasis, cough, headache, and hypokalemia.
Cefiderocol is contraindicated in patients with a known history of severe hypersensitivity to beta-lactam antibacterial drugs. Full prescribing information is available online. Cefiderocol was given priority review and qualified infectious disease product (QIDP) designations. QIDP designation is given to antibacterial products that treat serious or life-threatening infections under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act.