New data being presented at the upcoming ESCMID Global 2025 will show cefiderocol (Fetroja) had a higher clinical cure rate trend among patients who received cefiderocol for a documented infection (67.4%) or as empiric therapy (64.6%) as compared to those who received it as salvage therapy (58.2%).1
“These data suggest a trend towards worse clinical outcomes when the use of cefiderocol to treat gram-negative bacterial infections is reserved as a last line treatment option compared with those who received the treatment earlier. This trend may offer clinicians new evidence to justify the early and effective use of cefiderocol in patients with suspected resistant infections,” Oliver A Cornely, MD, Director of Translational Research, University of Cologne, said in a statement. 1
The study analyzed data from 567 patients hospitalized with confirmed gram-negative bacterial infections, who were treated with cefiderocol for the first time for ≥72 hours across Spain, France, Italy, Germany and the United Kingdom. Carbapenem resistance rate was >70% among patients enrolled in the study. 55.9% of patients were critically ill in the intensive care unit and 41.3% were receiving organ support at the point of cefiderocol initiation.1
Respiratory tract infection (RTI) was the most frequent infection site, reported in over 50% of patients (299), followed by urinary tract infection in over 12% of patients (73). Patients in the study receiving cefiderocol across all pathogens achieved an overall clinical cure rate of 65.3%.1 The most frequent pathogens observed were Pseudomonas aeruginosa (41.3%), Acinetobacter baumannii (15.0%) and Enterobacterales (14.6%), which are identified as priority pathogens by the World Health Organization.2 A clinical cure rate of 73.1% was observed among patients with a Pseudomonas aeruginosa infection.1
Learn more: Real-World Effectiveness of Cefiderocol in Treating Serious Gram-Negative Infections: Insights from the PROVE Study
The PROVE Study
The PROVE (Retrospective Cefiderocol Chart Review) study is a 5-year international, retrospective, observational medical chart review study, conducted between November 2020 and July 2024 designed to describe the efficacy and safety of real-world cefiderocol use in adult patients with serious gram-negative (GN) bacterial infections. This aforementioned data comes from the European cohort.1
In previous data reported at last year's IDWeek, cefiderocol demonstrated a clinical cure rate of 64% and a response rate of 71.6% by the end of treatment (EOT) in a study involving 1075 patients with carbapenem-resistant infections. Notably, 90.1% of these patients had at least 1 risk factor for their infections, and 59.8% were hospitalized in ICUs, with 48.1% requiring organ support.2
What You Need to Know
Patients treated with cefiderocol earlier—either for documented infections (67.4% cure rate) or empirically (64.6%)—experienced better clinical outcomes than those who received it as salvage therapy (58.2%).
The PROVE study analyzed 567 patients across multiple European countries. It found a 65.3% overall clinical cure rate, with even higher rates in certain subgroups (e.g., 73.1% for Pseudomonas aeruginosa infections).
Over 50% of patients had respiratory tract infections (RTIs), making it the most frequent infection site, followed by urinary tract infections. Cefiderocol showed variable success depending on infection type—with RTIs showing a 58% clinical cure rate and bloodstream infections (BSIs) performing slightly better.
Cefiderocol was administered as first-line therapy in 70.3% of cases, with a median treatment duration of 11 days. The most common site of infection was the respiratory tract, accounting for 54.1% of cases, with Pseudomonas aeruginosa (35.3%) and Acinetobacter baumannii (19.6%) identified as the most frequently occurring pathogens in monomicrobial infections.2
The study revealed varied outcomes based on infection type: patients with respiratory tract infections (RTIs) exhibited clinical cure and response rates of 58% and 68%, respectively, while those with bloodstream infections (BSIs) achieved slightly better rates of 66.7% and 74.1%. In terms of mortality rates, 31% of RTI patients and 18.5% of BSI patients succumbed to their infections by day 30. Among those infected with Pseudomonas aeruginosa, 67% achieved clinical cure, yet 22.3% died within the same timeframe.2
FDA Approvals
Cefiderocol is a cephalosporin antibiotic with a novel mechanism for penetrating the outer cell membrane of Gram-negative pathogens by acting as a siderophore. In addition to entering cells by passive diffusion through porin channels, cefiderocol binds to ferric iron and is actively transported into bacterial cells through the outer membrane via the bacterial iron transporters, which function to incorporate this essential nutrient for bacteria. These mechanisms allow cefiderocol to achieve high concentrations in the periplasmic space where it can bind to penicillin-binding proteins and inhibit cell wall synthesis in the bacterial cells.3
Cefiderocol was FDA approved in 2019, and was indicated in patients 18 years of age or older for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Enterobacter cloacae complex.4 The approval was later expanded for adult patients for the treatment of hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia.1
References
1. ESCMID Global 2025: Shionogi presents real-world data demonstrating better clinical outcomes when Fetcroja /Fetroja (cefiderocol) is used as empiric or documented therapy as compared to salvage therapy for the treatment of Gram-negative bacterial infections. April 9, 2025. Accessed April 10, 2025.
https://www.shionogi.com/us/en/news/2025/04/escmid-global-2025.html
2. Abene S. Real-World Effectiveness of Cefiderocol in Treating Serious Gram-Negative Infections: Insights from the PROVE Study. Contagion. October 19, 2024. Accessed April 10, 2025.
3.Contagion editorial team. FDA Approves Therapy for Hospital-Based Bacterial Pneumonias. Contagion. September 28, 2020. Accessed October 29, 2024.
https://www.contagionlive.com/view/fda-approves-therapy-for-hospitalbased-bacterial-pneumonias
4. FDA approves new antibacterial drug to treat complicated urinary tract infections as part of ongoing efforts to address antimicrobial resistance. FDA press release. November 14, 20019. Accessed April 10, 2025.
https://www.fda.gov/news-events/press-announcements/fda-approves-new-antibacterial-drug-treat-complicated-urinary-tract-infections-part-ongoing-efforts
