Real-World Experience with Cefiderocol in Hematologic Patients with Malignancies

OBJECTIVES: Given the limited real-world evidence in immunocompromised patients, we aimed to characterize cefiderocol use and outcomes in haematological patients. METHODS: Retrospective, multicenter study including consecutive haematological malignancy patients treated with cefiderocol (July 2022-March 2025) at two tertiary-level hospitals in Spain and Italy. RESULTS: Twenty-eight patients received cefiderocol; median age was 65.4 years, 50% male. Prior broad-spectrum antibiotics exposure occurred in 85.7% (24/28), and 57.1% (16/28) were colonized with multidrug-resistant (MDR) organisms. Cefiderocol was administered empirically in 53.5% (15/28) and as targeted therapy in 46.4% (13/28). Microbiological documentation obtained in 85.7% (24/28), with MDR pathogens in 75% (18/24). Pseudomonas aeruginosa was most frequent (13/28; 46.4%). Cefiderocol resistance occurred in 30.0% (3/10) of empirically gram-negative (GN) infections, and in 42.9% (3/7) of MDR-GNB cases, despite no prior exposure. One patient with necrotic skin P. aeruginosa infection developed resistance, with minimum inhibitory concentration increasing from 2 µg/mL to 64 µg/mL during follow-up. Two patients with MDR infections were clinically cured; however, new colonizations with cefiderocol-resistant P. aeruginosa and Verona integron-encoded metallo-β-lactamase (VIM)-producing K. pneumoniae developed during treatment. Overall 30-day mortality was 35.7%. CONCLUSIONS: Cefiderocol showed clinical response and no safety signal were identified in hematologic malignancy patients with MDR infections. However, emerging resistance requires research to optimize its role.