Sean Nguyen PharmD, BCIDP, medical director, Shionogi
Image Credit: Shionogi
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
The results from the trial are still being analyzed and reported. For example, new data was presented at the ESCMID Global 2025 that showed 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
In trying to glean more information, Contagion spoke to Sean Nguyen, PharmD, BCIDP, medical director, Shionogi who provided more data and insights on the European cohort of patients from the PROVE study.
Contagion: What does the PROVE study suggest about the effectiveness of early versus late use of cefiderocol in treating Gram-negative bacterial infections?
Nguyen: This study provides new data from a European cohort of patients from the PROVE study, the largest global real-world evidence study of cefiderocol.2 This study described the clinical cure rates* among patients who received cefiderocol as salvage, or rescue, therapy (after a prior antibiotic regimen had failed) and in patients who received cefiderocol earlier in their treatment – either for a confirmed infection (pathogen is known) or as empiric therapy (initial antibiotic regimen selected in the absence of pathogen identification). 2
Over half of the patients had a respiratory tract infection or were admitted to the intensive care unit at the initiation of cefiderocol treatment. 2 The results indicate a trend toward lower clinical cure rates in patients who received cefiderocol as a salvage therapy (58.2%), compared to those who were treated with cefiderocol as empiric (64.6%) or for a documented infection (67.4%).2 These findings provide important data to support the earlier use of cefiderocol for certain patients with difficult-to-treat Gram-negative bacterial infections rather than delaying its use when other agents have either failed or were non-susceptible to the infecting pathogen.
*Clinical cure was defined as resolution or improvement in infection signs and symptoms, without evidence of a later relapse or death
Contagion: How do clinical cure rates differ among patients with various infection types, such as respiratory tract infections and bloodstream infections, when treated with cefiderocol?
Nguyen: The overall clinical cure rate in this European cohort was 65.3%.2 Clinical cure rates varied by infection site: respiratory tract infection (59.2%), bloodstream infection (60.7%), urinary tract infection (90.4%), intra-abdominal infection (64.7%) and skin structure infection (63.9%).2
In the US, cefiderocol is FDA approved 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. It is also approved in patients 18 years of age or older for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by the following susceptible Gram-negative microorganisms: Acinetobacter baumannii complex, Escherichia coli, Enterobacter cloacae complex, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens.
In Europe, cefiderocol is approved for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.
Learn more: Cefiderocol Demonstrates Better Outcomes as Empiric or Documented Therapy as Compared to Salvage Therapy
Contagion: Given the high rate of carbapenem resistance and ICU admissions in the study population, what does this imply about the patient profile best suited for cefiderocol treatment?
Nguyen: The data contribute additional evidence supporting cefiderocol treatment for appropriate patients who are seriously ill with Gram-negative bacterial infections, including carbapenem-resistant infections. 2
The data at ESCMID extend our knowledge of cefiderocol in real-world settings from the data we previously presented at IDWeek last year.3 The data from IDWeek included patients from the US and EU, the majority of whom were in the intensive care unit and had a median age of 60. The data from IDWeek demonstrated that 67.5% had achieved a clinical cure with a 23.3% rate of 30 day all-cause mortality.3 Additional data presented at ESCMID contributes further evidence supporting cefiderocol treatment for certain patients who are seriously ill with carbapenem resistant Gram-negative infections but also demonstrates numerically higher clinical cure rates when cefiderocol is used earlier in these patients.2
Contagion: Why might Pseudomonas aeruginosa infections have shown a higher clinical cure rate compared to other pathogens in the PROVE study findings?
Nguyen: This subset analysis of the PROVE study consisted of 5 European countries including the United Kingdom, France, Spain, Germany and Italy where the typical patient profile receiving cefiderocol varied between the different countries.2 P aeruginosa accounted for more than half of the 448 monomicrobial infections, though the prevalence differed across countries.2 Although cefiderocol demonstrated favorableefficacy against P. aeruginosa, with a clinical cure rate of 73.1% and a 30-day all-cause mortality rate of 19.7%, correlation analyses have not been conducted as further analysis of the PROVE study is still underway.2
Contagion: Based on the observed trends and outcomes, how should clinicians approach the decision to use cefiderocol as a first-line versus salvage therapy?
Nguyen: With the full dataset presented at IDWeek along with the European cohort from ESCMID, these data provide clinicians with additional evidence that supports the safety and efficacy of cefiderocol in seriously ill patients across a variety of infection sites and different Gram-negative pathogens including in both monomicrobial and polymicrobial infections.2,3A majority of these patients had multiple risk factors for carbapenem resistance and the additional data presented at ESCMID demonstrate numerically higher clinical cure rates among patients treated with cefiderocol earlier as opposed to when it was used as a last-line treatment.2 The results provide clinicians with new evidence that supports the consideration of using cefiderocol in earlier lines of treatment in seriously ill patients who present with or have suspected risk factors for carbapenem-resistant infections rather than reserving itwhen other antibiotics are no longer an option.2
