PROTON PUMP INHIBITORS IN THE COMBINED TREATMENT OF PATIENTS WITH MULTIDRUG-RESISTANCE TUBERCULOSIS

Introduction. Prevalence of multidrug-resistance tuberculosis requires the use of repurposed drugs, considering the molecular mechanisms of drug resistance. Combining mycobacterium efflux pump inhibitors and anti- tuberculosis drugs appears to be a potential synergistic combination for the treatment of multidrug-resistance tuberculosis. Aim of the study was to examine the effectiveness of treatment of multidrug-resistance tuberculosis patients additionally managed with proton pump inhibitor in the intensive phase of chemotherapy, including new anti-tuberculosis drugs, bedaquiline and linezolid. Materials and Methods. A retrospective study was conducted in the medical records of 77 patients with infiltrative/disseminated multidrug-resistance tuberculosis/ pre-extensive drug resistance tuberculosis, who were divided into 2 groups,. The main group consisted of 35 patients with concomitant gastrointestinal pathology who, in addition to anti-tuberculosis therapy, received treatment with a proton pump inhibitor. The comparison group included 42 patients without gastrointestinal pathology who received only anti-tuberculosis therapy. Statistical data processing was performed using Microsoft Excel 2007 and Statistica 6.0 by both nonparametric and parametric methods. Results and Discussion. During therapy with a proton pump inhibitor, more pronounced favorable changes were detected in the underlying disease. None of the patients had adverse reactions to combined therapy with a proton pump inhibitor and anti-tuberculosis drugs. The achieved effect is associated with the ability of this drug to both inhibit the export of anti-tuberculosis remedies in mycobacteria and activate immunocompetent cells, i.e., macrophages, with an increase in their bactericidal properties. Conclusions. The use of a proton pump inhibitor in the intensive phase of chemotherapy regimens, including new anti-tuberculosis drugs bedaquiline and linezolid, in multidrug-resistance tuberculosis patients is safe and increases the frequency of closure of decay cavities and cessation of bacterial excretion (by 29.2% and 30.1% by the 4th month, respectively); as well as the elimination of clinical manifestations of the disease. The data obtained can be used in the development of combination tuberculosis therapy, considering the molecular mechanisms of drug resistance.