Fosfomycin Not Found Effective for Febrile Neutropenia Prevention, Suggests Research
Spain: In high-risk hematological patients, fosfomycin failed to show non-inferiority compared with ciprofloxacin for preventing febrile neutropenia. Its use was further discouraged due to a higher incidence of Gram-negative bacteremia associated with fosfomycin.
The findings are from the FOVOCIP phase 3 randomized clinical trial published in The Lancet Regional Health – Europe by Ahinoa Fernández Moreno and colleagues.
Patients with prolonged neutropenia following treatment for hematological malignancies or hematopoietic stem cell transplantation are highly vulnerable to severe bacterial infections. Fluoroquinolones such as ciprofloxacin are commonly used for antibacterial prophylaxis in these patients. However, concerns regarding antimicrobial resistance and adverse effects linked to fluoroquinolones have prompted researchers to explore safer and more effective alternatives.
To evaluate whether fosfomycin could serve as an alternative prophylactic antibiotic, investigators conducted a multicenter, randomized, open-label, phase 3 non-inferiority trial across 11 hospitals in Spain. Adult patients with acute leukemia or recipients of hematopoietic stem cell transplantation were randomly assigned to receive either oral fosfomycin or oral ciprofloxacin for infection prevention during high-risk neutropenia.
The study enrolled 166 patients, with 83 participants assigned to each treatment group. The primary outcome was the occurrence of febrile neutropenia. Researchers analyzed outcomes using both intention-to-treat and per-protocol populations.
The following were the key findings:
- Febrile neutropenia developed in approximately three-quarters of patients in both treatment groups.
- In the intention-to-treat analysis, success rates for remaining free from febrile neutropenia were 25.3% with fosfomycin and 26.5% with ciprofloxacin.
- Fosfomycin failed to meet the predefined criteria for non-inferiority compared with ciprofloxacin.
- The per-protocol analysis also showed that fosfomycin did not achieve non-inferiority versus ciprofloxacin.
- Gram-negative bacteria accounted for 90% of bacteremia episodes in the fosfomycin group compared with 10% in the ciprofloxacin group.
Researchers noted that the higher incidence of Gram-negative bacteremia further limits the clinical usefulness of fosfomycin in this patient population.
The investigators did note one potential microbiological advantage of fosfomycin. Colonization with multidrug-resistant Gram-negative bacteria occurred less frequently among patients receiving fosfomycin than among those receiving ciprofloxacin. However, the authors cautioned that the clinical relevance of this finding remains uncertain given the overall lower efficacy observed with fosfomycin prophylaxis.
The researchers noted that FOVOCIP was the first prospective randomized trial evaluating fosfomycin for infection prevention in neutropenic hematological patients and the first randomized comparison of an alternative antibiotic versus fluoroquinolones in this setting since 2005.
The authors suggested that the limited oral bioavailability of calcium fosfomycin may have contributed to its poor prophylactic efficacy and recommended further research on alternative oral formulations with better bioavailability.
The investigators concluded that finding effective alternatives to fluoroquinolones for neutropenic patients remains difficult and suggested that future studies should focus on other antibacterial strategies rather than calcium fosfomycin.
Reference:
Moreno, A. F., López de Ugarriza, P., González Huerta, A. J., Pascual, B. B., Cáceres, S., Blanco, L. S., Calabuig, M. L., Zarzuela, M. P., Rodríguez-Veiga, R., Montesinos, P., Fernández Verdugo, A. M., González-Barbera, E. M., Izquierdo, M., Medel-Plaza, M., Colomina, J., Olave, M. T., Humala, K., López, L., Labrador, J., . . . Bernal, T. (2026). Fosfomycin versus ciprofloxacin for febrile neutropenia prophylaxis in high-risk haematological patients (FOVOCIP): A phase 3, open-label, multicentre, randomised, non-inferiority trial. The Lancet Regional Health - Europe, 66, 101698. https://doi.org/10.1016/j.lanepe.2026.101698
Next Story