Cefiderocol is used to treat adults with complicated urinary tract infections, including kidney infections caused by susceptible Gram-negative microorganisms, who have limited or no alternative treatment options. In the United States, cefiderocol is indicated in adults 18 years of age or older who have limited or no alternative treatment options for the treatment of complicated urinary tract infections, including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Enterobacter cloacae complex. In the European Union, cefiderocol is indicated for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.
Adverse effects
An increased risk of dying was observed in people treated with cefiderocol as compared to other antibiotics in a separate clinical trial. Most of the deaths occurred in people hospitalized with other kinds of severe bacterial infections. The cause of death was not clear. Cefiderocol may cause serious and life-threatening allergic reactions, severe diarrhea caused by C. difficile and seizures. Labeling for cefiderocol includes a warning regarding the higher all-cause mortality rate observed in cefiderocol-treated people compared to those treated with other antibiotics in a trial in critically ill people 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 people treated for hospital-acquired/ventilator-associated pneumonia, bloodstream infections, or sepsis. The safety and efficacy of cefiderocol has not been established for the treatment of these types of infections.
Pharmacology
Mechanism of action
Its mechanism of entry into bacterial cells is by binding to iron, which is actively transported into the bacterial cells along with the cefiderocol. It is in a medication class known as siderophores, and was the first siderophore antibiotic to be approved by the U.S. Food and Drug Administration. It bypasses the bacterial porin channels by using the bacteria's own iron-transport system for being transported in.
History
In 2019, cefiderocol was approved in the United States as an antibacterial drug for treatment of adults 18 years of age or older with complicated urinary tract infections, including kidney infections caused by susceptible Gram-negative microorganisms, who have limited or no alternative treatment options. The safety and effectiveness of cefiderocol was demonstrated in a study of 448 participants with cUTIs. Of the participants who were administered cefiderocol, 72.6% had resolution of symptoms and eradication of the bacteria approximately seven days after completing treatment, compared with 54.6% in participants who received an alternative antibiotic. The clinical response rates were similar between the two treatment groups. The trial included participants from Europe, United States and Mexico. In the clinical trial, participants with cUTI were chosen at random to receive cefiderocol, or another antibacterial drug called imipenem/cilastatin. Both treatments were given intravenously for 7–14 days and neither the participants nor the health care professionals knew which drugs were given until after the trial was complete. Participants could not be switched to an oral antibacterial drug to complete the treatment for cUTI. The benefit of cefiderocol was measured by the proportion of participants who achieved cure or improvement in their symptoms related to cUTI and a negative urine culture test in comparison to imipenem/cilastatin. Cefiderocol received a Qualified Infectious Disease Product designation from the U.S. Food and Drug Administration and was granted priority review. The FDA granted approval of Fetroja, on 14 November 2019, to Shionogi & Co., Ltd. Cefiderocol was approved for medical use in the European Union in April 2020.
