The high prevalence of multidrug-resistant Acinetobacter baumannii has emerged as a serious problem in the treatment of nosocomial infections in the past three decades. Recently, we developed a new small-molecule inhibitor belonging to a class of 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones, Fluorothiazinon (FT, previously called CL-55). FT effectively suppressed the T3SS of Chlamydia spp., Pseudomonas aeruginosa, and Salmonella sp. without affecting bacterial growth in vitro. In this study, we describe that prophylactic use of FT for 4 days prior to challenge with resistant clinical isolates of A. baumannii (ABT-897-17 and 52TS19) suppressed septic infection in mice, resulting in improved survival, limited bacteraemia and decreased bacterial load in the organs of the mice. We show that FT had an inhibitory effect on A. baumannii biofilm formation in vitro and, to a greater extent, on biofilm maturation. In addition, FT inhibited Acinetobacter isolate-induced death of HeLa cells, which morphologically manifested as apoptosis. The mechanism of FT action on A. baumannii is currently being studied. FT may be a promising candidate for the development of a broad-spectrum antivirulence drug to use in the prevention of nosocomial infections.

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We studied the pharmacokinetics, tissue availability and metabolism of fluorothiazinon, a novel antivirulence drug, in mouse blood, liver, kidneys and lungs by administering the substance intragastrically at dose of 400 mg/kg. Fluorothiazinon was established to exhibit good tissue availability and long residential time. This drug is metabolized mainly by glucuronidation.

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To date, clinical data have convincingly shown that C. trachomatis and C. pneumoniae infectious can cause serious diseases with severe complications and consequences. There are assumptions that the developed chronic chlamydial infection can become an important factor in the pathogenesis of the gastrointestinal tract diseases, which are manifested in the so-called post-infectious period. It is commonly known that chlamydial infection has a tropism to the cylindrical epithelium, which covers the human mucous membrane of the urethra, cervix, rectum, conjunctiva of the eyes and the throat. However, the role of the causative agents of chlamydial infections, such as C. trachomatis and C. pneumoniae, in the occurrence of the gastrointestinal tract diseases has not been studied. In order to study the possible relationship between the gastrointestinal diseases and the presence of chlamydial infection markers, we have selected a group of patients with the gastrointestinal diseases and detected antibodies to C. trachomatis and C. pneumoniae and DNA of these pathogens in blood serum, liver biopsy and bile ducts. As a result, C. trachomatis DNA in blood serum was detected in 50% of cases, and in liver biopsies — in 59.3%. A new approach has been developed in the serological diagnosis of chlamydial infection caused by C. trachomatis, which allowed for revealing diagnostic antibody titers in 51.9% of cases in this group of patients, and in the comparison group — in 11.6% of cases. Among 50% of patients, in whom DNA was revealed in blood serum, it was also revealed in 64.3% of cases in biopsy samples of gastrointestinal organs. Upon detection of C. trachomatis DNA in blood serum, antibodies to the “cultural” antigen were detected in 60.1% of cases, and with the simultaneous detection of C. trachomatis DNA in blood serum and gastrointestinal organs, they were found in 72.2% of cases. Simultaneous detection of C. trachomatis, both in blood serum and in the gastrointestinal tract, may indicate the ability of C. trachomatis to spread hematogenously and infect organs away from the primary focus of infection. The obtained data absolutely require further study in light of the identification of the relationship between the detection of the pathogen and the development of the gastrointestinal pathology. But in general, the results are not yet studied evidence of the possible gastrointestinal organs infection by C. trachomatis.