Effectiveness and Safety of Cefiderocol in Clinical Practice for Treatment of Patients with Gram-Negative Bacterial Infections: US Interim Results of the PROVE Study

Cornelius J Clancy; Oliver A Cornely; Stephen W Marcella; Sean T Nguyen; Laurence Gozalo; Bin Cai

doi:10.2147/IDR.S475462

Effectiveness and Safety of Cefiderocol in Clinical Practice for Treatment of Patients with Gram-Negative Bacterial Infections: US Interim Results of the PROVE Study

Infect Drug Resist. 2024 Oct 15:17:4427-4443. doi: 10.2147/IDR.S475462. eCollection 2024.

Authors

Cornelius J Clancy¹, Oliver A Cornely^{2

3

4}, Stephen W Marcella⁵, Sean T Nguyen⁶, Laurence Gozalo⁷, Bin Cai⁸

Affiliations

¹ Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
² Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany.
³ Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany.
⁴ German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
⁵ Global Epidemiology and Real-World Evidence, Shionogi Inc, Florham Park, NJ, USA.
⁶ Medical Affairs, Shionogi Inc, Florham Park, NJ, USA.
⁷ Advanced Analytics, Genesis Research, Hoboken, NJ, USA.
⁸ Center of Real-World Data and Analytics, Shionogi Inc, Florham Park, NJ, USA.

Abstract

Purpose: The international PROVE retrospective chart-review study aims to assess the real-world effectiveness and safety of cefiderocol for treatment of patients with carbapenem-resistant Gram-negative infections.

Patients and methods: US centers selected hospitalized patients receiving their first cefiderocol treatment for ≥72 hours for a Gram-negative bacterial infection (November 2020-March 2023). Patient demographics, clinical characteristics, hospitalization, course of infection, antibiotic use, clinical cure (excluding patients with a relapse/reinfection), clinical response at the end of treatment, microbiology, in-hospital all-cause mortality (IH-ACM) at Day 30, and safety were analyzed using descriptive statistics.

Results: This interim analysis included 244 patients. The most frequent infection sites were respiratory tract (55.7%), skin and skin structure (16.8%), and blood (9.8%). The median duration of cefiderocol use was 12 days (interquartile range 8-18.5). Clinical cure was reported for 64.8% (158/244) of patients, clinical response for 74.2% (181/244), and 9.4% (23/244) had relapse/reinfection; 30-day IH-ACM was 18.4% (45/244). Of 82 patients with monomicrobial Pseudomonas aeruginosa infections, 64.6% (n = 53) and 74.4% (n = 61) had clinical cure and clinical response, respectively, and 30-day IH-ACM was 25.6%. Among 43 patients with monomicrobial Acinetobacter baumannii infections, 60.5% (n = 26) and 74.4% (n = 32) had clinical cure and clinical response, respectively, and 30-day IH-ACM was 18.6%. Five patients experienced six adverse drug reactions (one serious event: interstitial nephritis/acute kidney injury), and cefiderocol was discontinued in two cases.

Conclusion: Cefiderocol had similar clinical cure and response rates to previous retrospective studies and lower mortality. Cefiderocol was well tolerated in real-world settings in critically ill US patients with problematic Gram-negative pathogens.

Keywords: bloodstream infection; carbapenem resistance; cefiderocol; nonfermenters; real-world evidence; respiratory tract infection.

Grants and funding

This work was supported by Shionogi & Co., Ltd., Osaka, Japan.