Possibilities of Antibacterial Prevention of Ventilator-Associated Pneumonia Using the Non-Traditional Agent Fluorothiazinone

Background/Objectives: The global spread of multidrug-resistant pathogens complicates the treatment of ventilator-associated pneumonia (VAP), causing significant hospi-tal-acquired morbidity and mortality. This study was designed to evaluate the efficacy and safety of the non-traditional antibacterial drug Fluorothiazinone (FT) to prevent VAP caused by Gram-negative bacteria in patients on mechanical ventilation. Methods: We conducted a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial at 14 hospitals in Moscow and St. Petersburg. Treatment arm patients received FT at a dose: 2400 mg/day for the first 2 days and 1800 mg/day from the third day and further (but no more than 14 days) until the occurrence of VAP caused by gram-negative bacteria, confirmed clinically and microbiologically, or until the participant completed the study for other reasons. Results: Statistically significant differences were observed between the FT and placebo groups in the proportion of patients without clinically and microbiologically confirmed VAP caused by Gram-negative bacteria that developed 72-120 hours after tracheal intuba-tion and initiation of mechanical ventilation, as well as throughout the entire treatment period. Treatment with FT was associated with a 56% reduction in the risk of developing VAP, following adjustment for relevant clinical and demographic variables. Safety out-comes in the group receiving the study drug FT were not different from those in the place-bo group. Conclusions: The possibility of antibacterial prophylaxis with FT, to which resistance does not develop, which has a broad spectrum of action, a high degree of tissue distribu-tion, and a favorable safety profile, was demonstrated.