FDA approves cefiderocol for complicated UTIs including pyelonephritis

Cefiderocol is a siderophore cephalosporin. Its mechanism of entry and stability is active against all classes of β-lactamases, which enables it to overcome the primary mechanisms of gram-negative bacterial resistance to βlactam antibiotics.

The U.S. Food and Drug Administration approved Fetroja (cefiderocol) for treatment of patients 18 years of age or older with complicated urinary tract infections (cUTI) caused by susceptible Gram-negative microorganisms, who have limited or no alternative treatment options.

The FDA has granted approval of Fetroja to Shionogi & Co., Ltd.

"Today's approval provides an additional treatment option for patients with cUTIs who have limited or no alternative treatment options," said John Farley, M.D., M.P.H., acting director of the Office of Infectious Diseases in the FDA's Center for Drug Evaluation and Research. "A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. 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 Fetroja was demonstrated in a study of 448 patients with cUTIs. Of the patients who were administered Fetroja, 72.6% had resolution of symptoms and eradication of the bacteria approximately seven 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.

Labeling for Fetroja includes a warning regarding the higher all-cause mortality rate observed in Fetroja-treated patients compared to those treated with other antibiotics in a trial in critically ill patients with multidrug-resistant Gram-negative bacterial infections. The cause of the increase in mortality has not been established. Some of the deaths were a result of worsening or complications of infection, or underlying co-morbidities. The higher all-cause mortality rate was observed in patients treated for hospital-acquired/ventilator-associated pneumonia (i.e.nosocomial pneumonia), bloodstream infections, or sepsis. The safety and efficacy of Fetroja has not been established for the treatment of these types of infections.

The most common adverse reactions observed in patients treated with Fetroja included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion site reactions, candidiasis (yeast infection), cough, headache and hypokalemia (low potassium). Fetroja should not be used in individuals with a known history of severe hypersensitivity to beta-lactam antibacterial drugs.

Fetroja received the FDA's Qualified Infectious Disease Product (QIDP) designation. The QIDP designation is given to antibacterial and antifungal drug products intended to treat serious or life-threatening infections under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act. As part of QIDP designation, Fetroja was granted Priority Review under which the FDA's goal is to take action on an application within an expedited time frame.

For more information visit fda.gov.