Failure of Treatment of Patients with Pulmonary Tberculosis. Important Causes and Possible Ways to Eliminate Them (Review)

Objective — to determine the main causes of treatment failure in patients with pulmonary tuberculosis and to assess the effectiveness of parenteral administration of antituberculosis drugs (ATDs), considering their pharmacokinetics, bioavailability, and penetration into pathologically altered tissues. Materials and methods. A comprehensive literature review was conducted using PubMed, UkrINTEI, and Ukrainian National Scientific Periodicals, and other global databases. Experimental studies assessed serum concentrations, bacteriostatic activity, and minimum inhibitory concentrations (MICs) of oral rifampicin and intravenous rifamycin SV in 20 TB patients. The effectiveness of intravenous isoniazid and ethambutol was evaluated in 54 patients with TB/HIV co-infection meningoencephalitis. The study also included 73 patients with newly diagnosed pulmonary TB who experienced treatment failure after the intensive phase of therapy, as well as 20 healthy donors. All patients had drug-susceptible forms of tuberculosis. Results and discussion. Intravenous rifamycin SV achieved 2.5-fold higher peak serum concentrations and a tenfold lower MIC compared to oral rifampicin. Drug concentrations in pathological lesions (cavities, lymph nodes, tuberculomas) varied significantly depending on the drug and route of administration. In the group of patients who received intravenous ATDs, the rates of clinical improvement, sputum conversion, and cavity closure were significantly higher, while the rate of drug resistance was lower (p < 0.05). Conclusions. Parenteral administration of ATDs enables the achievement of therapeutic concentrations in blood and affected tissues, enhances treatment effectiveness, and reduces the risk of drug resistance. A personalised treatment approach with drug concentration monitoring is recommended for patients with gastrointestinal malabsorption or treatment failure after the intensive phase.