• Shabnam Naseer, Edward A Weinstein, Daniel B Rubin, Kalavati Suvarna, Xiaohui Wei, Karen Higgins, Avery Goodwin, Seong H Jang, Dmitri Iarikov, John Farley, and Sumathi Nambiar.
• Division of Anti-Infectives, Office of Infectious Diseases, Center for Drug Evaluation and Research, US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
• Clin. Infect. Dis. 2021 Jun 15; 72 (12): e1103-e1111.

AbstractIn November 2019, the Food and Drug Administration (FDA) approved cefiderocol for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis caused by susceptible gram-negative bacteria in adults with limited to no alternative treatment options based on a randomized, double-blind, noninferiority cUTI trial (APEKS-cUTI). In a randomized, open-label trial (CREDIBLE-CR) in patients with cUTI, nosocomial pneumonia, bloodstream infections, or sepsis due to carbapenem-resistant gram-negative bacteria, an increase in all-cause mortality was observed in patients treated with cefiderocol as compared to best available therapy. The cause of the increased mortality was not established, but some deaths were attributed to treatment failure. Preliminary data from a randomized, double-blind trial (APEKS-NP) in patients with nosocomial pneumonia due to carbapenem-susceptible gram-negative bacteria showed a similar rate of mortality as compared to meropenem. We describe the uncertainties and challenges in the interpretation of the CREDIBLE-CR trial and some benefit-risk considerations for the use of cefiderocol in clinical practice. Clinical Trials Registration: NCT02321800.Published by Oxford University Press for the Infectious Diseases Society of America 2020.

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