AMINOGLYCOSIDES IN THE TREATMENT OF MULTIDRUG-RESISTANT TUBERCULOSIS PATIENTS: ADVERSE EVENTS AND WAYS TO CORRECT THEM

Introduction. Some chemotherapy drugs, such as aminoglycosides, prescribed according to the drug sensitivity of the pathogen strains in the treatment of tuberculosis, , have an ototoxic effect. However, according to the pathogen sensitivity, aminoglycosides are the only drugs of choice. The main measure to prevent the development of ototoxicity is to identify risk factors and monitor hearing impairment, followed by the discontinuation or down–titration of ototoxic drugs, which is not enough to solve the problem. Currently, a search is underway for new ways to prevent ototoxicity in tuberculosis patients while maintaining existing chemotherapy regimens. Aim of the study was to assess the frequency of the development of adverse ototoxic reactions after the use of amikacin and the correctability of these reactions using a drug with a metabolic type of action. Materials and Methods. Information was recorded statistically in the regions of the Siberian and the Far Eastern Federal Districts of Russia. Drug resistance of Mycobacterium tuberculosis in patients’ sputum samples was detected using standard bacteriological and molecular genetic methods. A clinical bidirectional cohort randomized study included 60 tuberculosis patients divided into 2 groups: One group received amikacin along with standard anti–tuberculosis chemotherapy, and the other received the same with cytoflavin included in the regimen. Presence of complaints, medical history, results of examination by an otorhinolaryngologist, and hearing assessment using an AD226 audiometer were analyzed. Results and Discussion. Analysis of the drug resistance of Mycobacterium tuberculosis strains to first– and second–line anti–tuberculosis drugs in hospital patients according to our data for 2023 showed a high degree of their sensitivity to amikacin (71%). The incidence of adverse reactions to aminoglycosides was 70% in the institution in2021–2023. In TB dispensaries in the regions of Siberia and the Far East in 2021, sensorineural hearing impairment of varying degrees was detected in 14–220 people, and the data presented are greatly underestimated due to the lack of specialists and necessary equipment on site. Discontinuation of aminoglycosides when an undesirable ototoxic reaction occurs is not effective in accordance with relevant clinical recommendations, since hearing impairment progresses even after timely discontinuation of the toxic drug. It is shown that, when prescribing aminoglycosides to patients, simultaneously including in the treatment regimen a drug with the neurometabolic effect of cytoflavin helps prevent the development of ototoxicity. Conclusions. A reasonably high percentage of Mycobacterium tuberculosis strains are susceptible to aminoglycoside antibiotics, and their use is widespread in tuberculosis patients. Adverse events of ototoxicity are also common in this population. The findings of our studies demonstrate the efficacy of a new approach using neurometabolics in preventing the development of unwanted aminoglycoside–induced ototoxicity.