Cefiderocol Demonstrates Efficacy Against Pseudomonas in Immunocompromised

Back in 2020, the FDA approved a supplemental New Drug Application for the antibiotic, cefiderocol, (Fetroja), for treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible gram-negative microorganisms in patients 18 years of age or older. This was after cefiderocol (FDC) was initially approved for patients 18 years of age or older for the treatment of complicated urinary tract infections, including pyelonephritis, caused by gram-negative pathogens.¹

Within clinical management, there is not much data in the literature around using cefiderocol for treating multidrug-resistant gram-negative infections for those who are immunocompromised.

In a new, small study presented at the ongoing ESCMID, using cefiderocol, investigators reported a 57% (56/98 patients) efficacy with a resolution of infection by day 28 and 8 more were resolved by day 90.²

“We observed a trend towards the use of FDC for severe colistin-susceptible Pseudomonas infections in immunocompromised,” the investigators wrote.²

Read more: Evaluating Cefiderocol for Difficult-to-Treat, Gram-Negative Infections

Study Parameters and Methods
Cefiderocol is a cephalosporin antibiotic with a novel mechanism for penetrating the outer cell membrane of gram-negative pathogens by acting as a siderophore, and it is manufactured by Shionogi.

This was a retrospective multi-center cohort including adults with active solid cancers (SC), haematological malignancies (HM), hematopoietic stem cell transplantation (HSCT), solid organ transplantation (SOT), interstitial lung disease (ILD) under immunosuppressants and treated with cefiderocol between January 1 2020 and October 30, 2023. ²

The study included 98 patients, with 72 of them being males, from 11 medical centers. Of the various immunocompromised groups, 24 (24.5%) had SC, 36 (36.7%) had HM among whom 17 underwent HSCT, 34 (34.7%) SOT, 2 SOT with HM, and 2 ILD. The investigators reported the median age was 60-years of age.

Infections were monomicrobial in 71 cases (72.4%) and Pseudomonas aeruginosa accounted for 60 cases, other non-fermenting gram-negative bacteria for 40 cases and enterobacteria for 18 cases. Infection sites were lungs (n=48, 48.9%), urinary tract (n=12, 12.2%), gut (11, 11.2%), others (n=27, 27.5%) and associated with 37 (37.7%) blood stream infections. FDC was used alone in 46 cases (47.4%).

References
1.Parkinson J. Time-to-Treat Proves to be Vital in Severely Ill Patients With Gram-Negative Infections. Contagion. October 23, 2023. Accessed April 29, 2024.

2.Soueges S et al. Retrospective multicenter cohort of immunocompromised patients treated with cefiderocol for infections caused by multidrug-resistant Gram-negative bacteria. Oral abstract. Presented at ESCMID. April 27-30, 2024. Barcelona, Spain.