Novel Siderophore Cephalosporin Nets Promising Results in Tough-to-Treat CRAB

WASHINGTON – Cefiderocol (Fetroja) may be a viable targeted-therapy option in critically ill patients with carbapenem-resistant Acinetobacter baumannii infections (CRAB), according to the ongoing PROVE trial.

In the real-world setting, patients with CRAB often had multiple comorbidities, including severe burns, which complicates therapy, explained Stephen Marcella, MD, of Shionogi in Florham Park, New Jersey.

He reported that 61% of 41 patients in PROVE were given cefiderocol in the ICU, and 51% required mechanical ventilation, while 34% required vasopressor support, suggesting the critical nature of their condition.

Treatment with at least 72 hours of cefiderocol led to clinical cure of the infection in 59%; 22% died within 30 days of treatment. All-cause mortality in treated patients at 14 days was 12%; at 30 days it was 22%, Marcella reported in a poster presentation at IDWeek.

Christian Sandrock, MD, of the University of California Davis at Sacramento noted that "cefiderocol is [FDA] approved for treatment of patients with these Gram-negative infections, mainly pneumonias. A. Baumannii is one of those infections and another big one is Pseudomonas. PROVE is a real-world study, and sometimes what happens in the real-world differs from clinical trials, which may not really represent what we do at the bedside."

Sandrock, who was not involved in the trial, said PROVE data give clinicians more treatment options in the "types of patients we really see: The sick ones, with multiple issues going on and who have received multiple antimicrobials, and who are resistant to fluoroquinolones, meropenem, cephalosporins and beta lactams, which basically blow out every reliable antibiotic group. So because we have drugs like cefiderocol, it gives us comfort that we have something we can fall back on to use in some of these patients."

Among 41 patients, 29 were infected only with A. baumannii, while 12 were infected with A. baumannii and other pathogens. All but one was diagnosed with CRAB. Median patient age was 53 and 71% were men. Less than a fourth were hospitalized with burns and that was the single most frequent comorbidity, Marcella said.

The authors reported that the median time from positive culture to cefiderocol initiation was 5 days, and about 62% received monotherapy with cefiderocol. Tetracyclines were the most common concurrent Gram-negative antibiotics used with cefiderocol.

In 2019, FDA approved the antibacterial drug for treatment of adults with complicated urinary tract infections, including kidney infections caused by susceptible Gram-negative microorganisms. The agent turned in promising results in a 2022 study from Italy that compared cefiderocol with colistin in patients with CRAB.