EFFECTIVENESS AND SAFETY OF CEFIDEROCOL IN THE TREATMENT OF ORTHOPEDIC IMPLANT INFECTIONS BY EXTENSIVELY DRUG-RESISTANT GRAM-NEGATIVE BACTERIA

Introduction Cefiderocol is a novel siderophore cephalosporin which is effective against multidrug resistant (MDR) and extensively drug resistant (XDR) Gram negative bacteria (GNB) producing carbapenemases (CP). The drug is licensed for nosocomial pneumonia, complicated urinary tract and bloodstream infections. Few data exist for its safety and efficacy in the prolonged treatment of orthopedic implant infections. We aim to present our clinical experience with the off-labeled, salvage use of the drug in patients with orthopaedic implant infections by XDR GNB. Patients-Methods An observational study of consecutively hospitalized patients treated with cefiderocol for orthopedic implant infections caused by MDR/XDR GNB was launched from July 2025 to March 2026. Patients' demographics, type of infection, pathogens, length of treatment and outcome were recorded. Cured patients had no relapse of infection during follow up. Results Five patients (male, n=3; female, n=-2) with periprosthetic joint infection (PJI, n=1), external osteosynthesis (n=1), internal osteosynthesis (n=3) of lower arms (femoral/tibial implants) were assessed. Clinical isolates were retrieved from intraoperative tissue (n=4) and blood (n=1) cultures; all were CP strains : Acinetobacter baumannii XDR (n=3), Pseudomonas aeruginosa NDM (n=1), Serratia marcescens VIM (n=1). Surgical debridement with implant removal was performed in 75% of cases with re-implantation in 3 cases. Co-administration with other antibiotics (tigecycline, ampicillin/sulbactam, fosfomycin) was performed in 4 cases. The mean duration of cefiderocol treatment was 18.6 days (range 10-42 days). In 2 cases, cefiderocol was replaced by other available antibiotic, due to temporary lack of the drug. Two patients presented grade 1 side effects correlated with cefiderocol which resolved without treatment discontinuation. Overall, during a 3 month post-treatment follow up only one patient presented with infection relapse, therefore the administratin of the drug has contributed to treatment success. Conclusion Prolonged (more than 14 days) treatment with cefiderocol combined with other potent antibiotics is a safe and promising choice for patients with orthopedic implant infections by XDR GNB in hospital settings with high endemicity of antimicrobial resistance along with prompt surgical therapy.