Cefiderocol for Stenotrophomonas maltophilia infections: real-world evidence from a multicenter study and a comprehensive literature review

Purpose: Stenotrophomonas maltophilia is an opportunistic, multidrug-resistant (MDR) pathogen increasingly implicated in severe infections, particularly among immunocompromised and critically ill patients. Cefiderocol, a novel siderophore cephalosporin, has shown promising in-vitro activity against S. maltophilia, but real-world clinical data remain still limited. Methods: This retrospective, multicenter case series analyzed adult patients with severe S. maltophilia infections treated with cefiderocol across three tertiary-care hospitals from November 2021 to November 2024. The primary endpoints included 30-day all-cause mortality, clinical cure, microbiological eradication and cefiderocol-related adverse events. Results: Fourteen patients were included. The median age was 61 years (IQR 52.5–73), 64.3% were female, median Charlson Comorbidity Index (CCI) was 5 (IQR 2-7). Infection types were mainly pneumonia [50%, including ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP)], followed by complicated intra-abdominal infections (14.3%) and septic thrombosis (14.3%). Of the remaining patients, 1 had a urinary tract infection (UTI), 1 a central line-related bloodstream infection (BSI) and 1 pulmonary empyema (7.1% each). Polymicrobial infections were detected in 42.9% of cases. Resistance to TMP-SMX and levofloxacin was 35.7% and 8.3%, respectively. Clinical cure was achieved in 64.3%, microbiological eradication in 75%, and 30-day mortality was 21.4%. No adverse events attributable to cefiderocol were observed. Conclusion: cefiderocol represents an effective and well-tolerated treatment for severe S. maltophilia infections, including polymicrobial cases and critically ill patients. These findings support its use, particularly in the context of resistance to conventional therapies. Further large-scale prospective studies are warranted to confirm these observations.