Real-World Data on the Effectiveness and Use of Intravenous Fosfomycin for the Treatment of Difficult-to-Treat Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria-A Subgroup Analysis from the FORTRESS Study.

Abstract

Introduction: This subgroup analysis of the FORTRESS study aimed to evaluate clinical and microbiological outcomes, treatment patterns, and safety of intravenous fosfomycin (FOS)-containing regimens for the treatment of infections due to carbapenem-resistant (CR) Gram-negative bacteria in a real-world setting.

Methods: Interim data from patients treated with FOS for infections due to CR pathogens were analyzed from the ongoing prospective, multicenter, multinational, observational FORTRESS study. Key outcomes included patient demographics, clinical and infection characteristics at baseline, treatment patterns, and indications of FOS use, as well as clinical, microbiological, and safety outcomes. Exploratory Firth univariate and multivariate logistic regression were performed to identify factors associated with successful clinical response.

Results: The subgroup included 161 patients (median age 60 years, 30.4% female, median APACHE II score 15), of whom 59.6% required intensive care, and 41.6% had sepsis at baseline. The most common indications for FOS therapy were hospital-acquired/ventilator-associated pneumonia (28.0%), bacteremia/sepsis (26.1%), and complicated urinary tract infections (24.8%). Infections were predominantly caused by Klebsiella pneumoniae (62.7%), Pseudomonas aeruginosa (28.6%), and Acinetobacter baumannii (17.4%). Carbapenem resistance was mainly mediated by Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM). In the majority of patients, FOS was part of a combination regimen (91.3%), with ceftazidime-avibactam being the most frequently used partner antibiotic. Overall, clinical success was achieved in 79.4% of patients, while the successful clinical response and microbiological cure rates were 87.5% and 81.3% at the end of FOS treatment, respectively. All-cause in-hospital mortality was 9.9%. Electrolyte imbalances were the most commonly reported adverse drug reactions, but they were mostly not treatment-limiting.

Conclusions: The real-world data of this subgroup analysis suggest that FOS-containing regimens were associated with generally favorable clinical and microbiological outcomes and acceptable tolerability in patients with severe infections due to CR Gram-negative bacteria.