Antibacterial drug fortiazinon for the treatment of complicated and chronic urinary tract infections

Introduction. The relevance of complicated urinary tract infections (cUTIs) is determined by their high prevalence, recurrent course, and the frequent resistance of pathogens to standard antibacterial regimens. Therefore, the clinical evaluation of new antimicrobial agents (fortiazinon) is one of the promising directions for improving the treatment of cUTIs.

Materials and Methods. A prospective, multicenter, randomized, placebo-controlled clinical trial was carried out in two groups of patients with cUTIs who received either a combination of cefepime with fortiazinon or cefepime with placebo. Cefepime 1 g was administered intravenously or intramuscularly every 12 hours; fortiazinon 600 mg (2 tablets of 300 mg) or placebo (2 tablets) was administered orally every 12 hours immediately after cefepime. The treatment duration was 7 days, with the possibility of extension up to 14 days at the discretion of investigators. A total of 357 patients were included: 180 received cefepime + fortiazinon, 177 received cefepime + placebo. The primary endpoint was the proportion of patients with clinical and microbiological cure at day 21 after completion of treatment. Secondary endpoints included clinical efficacy in subgroups (MITT, mMITT, CE), pathogen eradication in microbiologically confirmed cUTIs, and recurrence rates at days 60 and 90 after therapy.

Results. The primary endpoint was achieved in 136/180 (75.6%) of patients treated with cefepime/fortiazinon and in 90/177 (50.8%) of those treated with cefepime/placebo (difference: 24.7%; 97.5% CI: –14.7; two-sided ANOVA test). Analysis of secondary endpoints revealed significant advantages in clinical cure rates: MITT by 21.7%, mMITT by 21.5%, CE by 18.8%, and pathogen eradication by 13.2%. During follow-up, recurrence rates were significantly lower in the fortiazinon group compared with placebo: at day 60 the rates were 1.1% and 16.0%, and at day 90 they were 2.8% and 21.7%, respectively. Adverse events occurred in 37 (20.6%) patients receiving fortiazinon and in 26 (14.7%) patients in the placebo group (difference was insignificant). The most frequent adverse events were sleep disturbances, elevated alanine aminotransferase activity, and increased serum bilirubin. All adverse events were mild, did not require treatment, and did not lead to discontinuation of therapy.

Conclusion. Cefepime/fortiazinon was significantly superior to cefepime/placebo in the treatment of complicated urinary tract infections and in the prevention of recurrence during follow-up.