In order to combat resistance, it is necessary to develop antimicrobial agents that act differently from conventional antibiotics. Fluorothiazinone, 300 mg tablet (The Gamaleya National Research Center), is an original antibacterial drug based on a new small molecule T3SS and flagellum inhibitor. A total of 357 patients with complicated urinary tract infections (UTIs) were divided into two groups and given Fluorothiazinone 1200 mg/day or a placebo for 7 days to evaluate the efficacy and safety of the drug. Additionally, all patients were given Cefepime 2000 mg/day. Fluorothiazinone with Cefepime showed superiority over placebo/Cefepime based on the assessment of the proportion of patients with an overall outcome in the form of a cure after 21 days post-therapy (primary outcome), overall outcome in cure rates, clinical cure rates, and microbiological efficacy at the end of therapy and after 21 days post-therapy (secondary outcomes). In patients who received Fluorothiazinone, the rate of infection recurrences 53 and 83 days after the end of the therapy was lower by 18.9%, compared with patients who received placebo. Fluorothiazinone demonstrated a favorable safety profile with no serious unexpected adverse events reported. The results showed superiority of the therapy with Fluorothiazinone in combination with Cefepime compared with placebo/Cefepime in patients with cUTIs.

Background/Objectives: New data on the pathogenesis of recurrent urinary tract infections (rUTIs) and the growing level of bacterial resistance to antibiotics require a revision of patient treatment strategies and a search for non-antibiotic approaches to the treatment and prevention of UTIs. The aim of this study was to investigate the clinical and microbiological efficacy of a new, non-traditional antibacterial drug, Fluorothiazinone (FT). Methods: We conducted an open-label, randomized, multicenter cohort clinical trial, phase III, at 12 hospitals in Moscow and St. Petersburg. 280 patients were randomized into two groups in a 1:1 ratio to receive FT at a dose of 1200 mg/day for 14 days or furadoninat a dose of 400 mg/day for 7 days. Clinical and microbiological cure were assessed 7, 14 and 28 days after the start of therapy. Results: For the primary efficacy end-point, clinical cure at day 28, the recovery rate was 91.7% in patients receiving FT and 92.8% in patients receiving furadonin, the hypothesis of non-inferiority of FT compared to the standard furadonin regimen was confirmed by two-sided 95% confidence intervals. The proportion of patients with clinical cure on days 7 and 14 also did not differ in the two groups. An assessment of microbiological eradication at all observation times in our study demonstrated that FT, whose mechanism of action is associated with the suppression of pathogen virulence, possesses antibacterial activity comparable to that of the antibiotic furadonin leading to the eradication of pathogens causing rUTIs. The frequency of microbiological relapses after 28 days of treatment was 19.6% in the group receiving FT and 22.2% in the group receiving furadonin. Both study groups were comparable in the severity of adverse events (AEs). A definite relationship with the study drugs was identified for 1 (11.1%) AEs after taking FT and 8 (88.9%) AEs after taking furadonin.Conclusions: Clinical trials in patients with recurrent cystitis have demonstrated the intrinsic antibacterial activity of FT, equal clinical and microbiological efficacy compared to first-line drugs for the treatment of recurrent cystitis, as well as a high level of safety, indicating the potential for the use of drugs with a new mechanism of action in the context of growing antibiotic resistance.

Background/Objectives: New data on the pathogenesis of recurrent urinary tract infections (rUTIs) and the growing level of bacterial resistance to antibiotics require a revision of patient treatment strategies and a search for non-antibiotic approaches to the treatment and prevention of UTIs. The aim of this study was to investigate the clinical and microbiological efficacy of a new, non-traditional antibacterial drug, Fluorothiazinone (FT). Methods: We conducted an open-label, randomized, multicenter cohort clinical trial, phase III, at 12 hospitals in Moscow and St. Petersburg. A total of 280 patients were randomized into two groups in a 1:1 ratio to receive FT at a dose of 1200 mg/day for 14 days or furadonin at a dose of 400 mg/day for 7 days. Clinical and microbiological cures were assessed 7, 14, and 28 days after the start of therapy. Results: For the primary efficacy endpoint, clinical cure at day 28, the recovery rate was 91.7% in patients receiving FT and 92.8% in patients receiving furadonin, the hypothesis of non-inferiority of FT compared to the standard furadonin regimen was confirmed by two-sided 95% confidence intervals. The proportion of patients with clinical cure on days 7 and 14 also did not differ in the two groups. An assessment of microbiological eradication at all observation times in our study demonstrated that FT, whose mechanism of action is associated with the suppression of pathogen virulence, possesses antibacterial activity comparable to that of the antibiotic furadonin, leading to the eradication of pathogens causing rUTIs. The frequency of microbiological relapses after 28 days of treatment was 19.6% in the group receiving FT and 22.2% in the group receiving furadonin. Both study groups were comparable in the severity of adverse events (AEs). A definite relationship with the study drugs was identified for 1 (11.1%) AE after taking FT and 8 (88.9%) AEs after taking furadonin. Conclusions: Clinical trials in patients with recurrent cystitis have demonstrated the intrinsic antibacterial activity of FT, equal clinical and microbiological efficacy compared to first-line drugs for the treatment of recurrent cystitis, as well as a high level of safety, indicating the potential for the use of drugs with a new mechanism of action in the context of growing antibiotic resistance.

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.