Fosfomycin combination therapy in high-risk paediatric patients with multidrug-resistant infections: a retrospective study

Intravenous fosfomycin is a broad-spectrum, bactericidal antibiotic active against Gram-positive and Gram-negative bacteria, including multidrug-resistant (MDR) strains. Evidence regarding its use in paediatric patients, particularly as part of combination therapy, remains limited. This study aimed to evaluate the safety and clinical outcomes of intravenous fosfomycin-based combination therapy in children. We conducted a single-centre, retrospective study including paediatric patients aged 0-18 years who received IV fosfomycin at Regina Margherita Children's Hospital in Turin between July 2019 and April 2025. Patients with underlying comorbidities, immunosuppression, invasive devices, or prematurity were included. Fifty paediatric patients were enrolled, with a median age of 5.93 years and balanced sex distribution. Comorbidities were present in 80% of cases, and 56% had primary or acquired immunodeficiency. Fosfomycin was always used in combination therapy for confirmed bloodstream infections (54%), osteoarticular infections (12%), skin and soft tissue infections (8%), or other infections (24%). Microbiological identification was achieved in 90% of cases: 53.4% Gram-negative and 46.6% Gram-positive bacteria. Half of the isolated pathogens were MDR, including ESBL, CPE, MDR Pseudomonas aeruginosa, XDR and MDR Gram-positive bacteria. Five patients died, and therapeutic failure-defined as death, relapse, or failure to achieve microbiological clearance-occurred in 28% of cases. IV fosfomycin was well tolerated, and no adverse effects requiring treatment discontinuation were reported. Conclusions: In a cohort of vulnerable paediatric patients with severe underlying conditions and difficult-to-treat infections, IV fosfomycin-based combination therapy was well tolerated and associated with acceptable clinical outcomes. Its use should be considered a rescue therapy for infections resistant to standard treatment.