Introducing Cefiderocol Earlier in Difficult-to-Treat-Infections

In data being presented at the ongoing IDWeek, analysis of the US cohort of the PROVE study assessed clinical cure rates in mostly seriously ill patients treated with cefiderocol. The overall clinical cure rate for infections across different infection sites was 70.1%.¹ Additionally, the clinical cure rate was 73.7% among patients who received cefiderocol before the causative bacteria had been identified (empiric treatment).

In terms of the study’s participants, 57.3% of them were in the intensive care unit and 47.6% were receiving organ support, including mechanical ventilation or use of vasopressor medication at cefiderocol initiation.

Clinical cure has been defined as resolution or improvement of signs or symptoms with no subsequent signs of relapse or mortality. The analysis included 508 patients in the US with serious infections caused by Gram negative bacteria who received cefiderocol for the first time and for at least 72 hours (median of 10 days). Respiratory tract infections were the most common infections (53.5%), followed by skin and skin structure infections (14.6%) and bloodstream infections (9.3%). 

Cefiderocol was effective across a range of serious infections caused by Gram negative pathogens; the most frequent monomicrobial infections observed were from Pseudomonas aeruginosa (29.9%), Acinetobacter baumannii (21.7%), Enterobacterales (11.4%), and Stenotrophomonas maltophilia (4.9%).¹ Cefiderocol was also effective across polymicrobial infections, which represented 29.9% of infections in this analysis.

"I think the biggest message about PROVE is that after several years of being used in the real world is that cefiderocol retains excellent activity against the most difficult-to-treat infections that we face, and then I think with that, it's also retained high levels of antibiotic activity with low levels of resistance to these problematic pathogens,” said Cornelius (Neil) Clancy, MD, professor of medicine at the University of Pittsburgh, who presented the findings at the conference.

This analysis was part of the PROVE’s ongoing studies conducted around cefiderocol. With data released earlier looking at a European population.

“What really struck me when we put the PROVE data from the US together for this meeting is really how they echo and build upon the European data that were presented earlier. And I think really in both the European and the US data, what you're seeing is excellent clinical cure rates. So keep in mind again, these are the most difficult-to-treat infections that we have with highly resistant bacteria,” Clancy said.

Introducing the Therapy Earlier

Although the clinical cure rate was lower (54.3%) when cefiderocol was used as salvage therapy, Clancy points to the severity of illness these patients have and provides clinical evidence to introduce the agent earlier.

“For every hour that you introduce a drug earlier, you reduce the mortality rate. And an hour's delay is typically associated with up to 10% to 12% increase in mortality rate. So earlier is better. What we try to teach people in our practice—and the PROVE data support this—is if you have a reasonable suspicion to believe that a highly resistant Gram negative infection is in play, and cefiderocol might be appropriate for your patient, the time to start is immediately," Clancy said. "As you get your data back, as the patient's case evolves, you can reassess and do what you think you need to do. Cefiderocol is not a drug that you're going to use in every hospitalized patient, but among those patients who are most at risk for your most difficult-to-treat Gram negative infections, getting them on board earlier does improve outcomes."

About the Antibiotic

Cefiderocol is an innovative siderophore cephalosporin for the treatment of seriously ill adult patients with complicated urinary tract infections (cUTIs) and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by certain Gram negative bacterial infections.

Reference
Clancy C, et al. Earlier Cefiderocol Use Was Associated with Better Outcomes for Challenging Gram-Negative Bacterial Infections: US Results From the Global Observational PROVE Study. Poster presented at IDWeek 2025. Poster #P-1353.