The ongoing PROVE retrospective chart review study aims to assess real-world outcomes of cefiderocol treatment in patients with serious Gram-negative bacterial infections. At IDWeek, Cornelius (Neil) Clancy, MD, a professor of medicine at the University of Pittsburgh, presented findings demonstrating that cefiderocol has proven to be both effective and well-tolerated in treating serious Gram-negative bacterial infections in real-world settings, particularly among patients with high rates of ICU admissions and the need for organ support.
“These are serious infections in very sick patients,” Clancy noted. “The PROVE study had two primary major findings. One is that overall, it was quite effective in treating these very difficult-to-treat infections, which were largely caused by priority pathogens identified by WHO, such as Pseudomonas and Acinetobacter. These pathogens are associated with high rates of resistance to other antibiotics. The clinical success rate in the study overall was 75%, which is extremely good, and clinical success was observed in various types of
Infections, respiratory tract infections, urinary tract infections, and bloodstream infections.”
The study involving 1,075 patients with carbapenem-resistant infections, cefiderocol emerged as a key treatment option, demonstrating a clinical cure rate of 64% and a response rate of 71.6% by the end of treatment (EOT). Notably, 90.1% of these patients had at least one risk factor for their infections, and 59.8% were hospitalized in ICUs, with 48.1% requiring organ support.
Clancy continued, “We have very encouraging real-world data regarding the types of infections that clinicians are treating in hospitals throughout the country and around the world. The second major finding was how well tolerated, and safe the drug appeared. In over 1,000 patients, there were a total of three serious adverse drug reactions and only 13 patients discontinued use of the drug. This combination of safety and efficacy for the most difficult-to-treat infections we have is quite promising and offers a strong complement to previously published randomized clinical trial data.”
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.
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.
“I think the real-world data that are presented in the PROVE study are a complement to randomized clinical trial data, which were used to get approval and for regulatory reasons for the drug initially, and they reflect really more realistically how the drug is and will be used in real patients in real-world settings,” Clancy stated.
Regarding infection complexity, clinical cure rates were 63.6% for monomicrobial infections and 65% for polymicrobial infections. The all-cause mortality (ACM) rates at days 14 and 30 were 15.6% and 24.3%, respectively, with ACM rates at day 30 of 25.6% for monomicrobial and 20% for polymicrobial infections.
Clancy concluded, “With any new drug, as more experience is gathered with using cefiderocol across different types of infections, bacteria, and patient populations, we’ll continue to understand where it fits within the armamentarium. What the PROVE study shows is that when used appropriately for the correct types of infections, there is a role for cefiderocol in treatment that patients will tolerate it well and it’s safe.”
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