Real-world effectiveness and safety of cefiderocol in critically ill patients with MDR Gram-negative infections: Results from a retrospective study

The increasing prevalence of multidrug-resistant (MDR) Gram-negative bacteria, particularly Acinetobacter baumannii (A. baumannii), represents a major clinical challenge, especially in critically ill patients. Cefiderocol, a siderophore cephalosporin, has emerged as a promising therapeutic option for infections caused by carbapenem-resistant organisms. The present study aimed to evaluate the real-life efficacy and safety of cefiderocol in a high-risk hospital population. A monocentric, retrospective observational study was conducted at the University Hospital ‘Gaetano Martino’ in Messina, Italy, from July 2021 to April 2022. Adult patients treated with cefiderocol for ≥48 h for documented or suspected infections caused by MDR Gram-negative bacteria were included. Primary endpoints were clinical resolution and mortality at discharge. Secondary outcomes included adverse drug reactions, hospital epidemiology of MDR organisms, and correlation with colonization status. Data were analyzed using descriptive and inferential statistics. A total of 55 patients were included, with a median age of 65 years; 67.3% were male. Most infections were pneumonia (80.0%) and bloodstream infections (BSI; 45.5%). A. baumannii was the most frequently isolated pathogen (87.3%), with 73.7% being extensively drug-resistant. Clinical success was observed in 40% of ventilator-associated pneumonia, 66.7% of BSI, and 100% of skin and soft tissue infections. Overall mortality was 47.3%, significantly associated with colonization by MDR organisms (P=0.028) and septic shock (P=0.001). No serious adverse events related to cefiderocol were reported. In conclusion, in a real-world setting involving severely ill patients with limited therapeutic options, cefiderocol showed favorable efficacy and favorable tolerability, particularly in bloodstream and soft tissue infections. These results support its role as a valuable treatment option for MDR Gram-negative infections, especially in intensive care unit settings, although further controlled studies are warranted.