Cefiderocol Targeted Treatment for Multidrug-Resistant Gram-Negative Infections: An Observational Cohort Study

Background/Objectives: Infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a major therapeutic challenge, particularly in hospitalized and critically ill patients with limited treatment options. Cefiderocol, a novel siderophore cephalosporin, has demonstrated activity against a broad range of resistant Gram-negative pathogens. We aimed to evaluate the effectiveness and safety of cefiderocol for the treatment of MDR-GNB infection. Methods: We conducted a retrospective observational study including all adult patients who received ≥72 h of cefiderocol between November 2020 and October 2024 at a Spanish tertiary-care hospital. The primary outcome was clinical success, defined as survival and absence of clinical recurrence 30 days after cefiderocol initiation. Secondary outcomes included 30- and 90-day mortality, clinical and microbiological recurrence, emergence of resistance, and adverse events. Results: Eighty patients were included (median age 64 years IQR 56–72; 81.3% male). Respiratory (26.2%) and abdominal (22.5%) infections were the most common, and 20% presented with bacteremia. At infection onset, 26.2% had septic shock and 45% required intensive care unit admission. The three most frequently isolated pathogen was Pseudomonas aeruginosa (33.9%), followed by Enterobacterales (33%) and Stenotrophomonas maltophilia (30.1%). Clinical success was achieved in 67.5% of patients. Thirty and 90-day mortality rates were 27.5% and 36.5%, respectively. Recurrence within 90 days occurred in 5% of cases. Emergence of resistance was detected in one Klebsiella pneumoniae ST147 isolate, and serious adverse events occurred in 5% of patients. Conclusions: In a cohort including a substantial proportion of critically ill patients, cefiderocol was associated with favorable clinical outcomes and an acceptable safety profile. These findings suggest that cefiderocol may represent a useful therapeutic option for severe MDR-GNB infections in patients with limited treatment alternatives.