The development of drug-resistant tuberculosis is observed not only in patients who had previously received treatment due to inappropriate choice or irregular medication use, but also in newly diagnosed patients due to the transmission of resistant strains of M. tuberculosis. The treatment of drug-resistant tuberculosis requires the use of reserve drugs, the right choice of which is only possible if the results of a study of the susceptibility of the pathogen to anti-tuberculosis drugs are available. In many areas with a high prevalence of drug-resistant tuberculosis, newly diagnosed patients with tuberculosis caused by resistant or even multidrug-resistant mycobacteria receive empirical treatment with first-line drugs. This is due to the low availability of reserve drugs and the lack of conditions to determine the sensitivity of the pathogen and the duration of response when using traditional methods.
Direct observation therapy (direct observation therapy, DOT) recommended by the World Health Organization (WHO) involves the use of standard short-term chemotherapy courses in newly diagnosed patients with of tuberculosis. Short courses are less effective for drug-resistant tuberculosis. In addition, the development of resistance to new drugs in initially resistant strains of M. tuberculosis is possible with inadequate DOT modes.
In the Tomsk region, the incidence of tuberculosis with a positive sputum test is 47.7 per 100,000 population. The prevalence of drug-resistant tuberculosis in newly diagnosed patients is quite high - 29%.
A directly observed treatment has been used in Tomsk since 1994. The study of the sensitivity of the pathogen was carried out in all newly diagnosed patients. During the period 1996-2000. The supply of first-line drugs was stable, but there was a shortage of reserve drugs, so patients received short-term chemotherapy courses even with resistance to pathogens detected. The current situation has made it possible to assess the effect of primary resistance M. tuberculosis on the effectiveness of treatment and the emergence of resistance to new drugs during the use of short-term standard chemotherapy.
A retrospective study involved 2194 patients who underwent treatment between 1996 and 2000. and received a short course of chemotherapy. Prisoners with tuberculosis were not included in the study. The diagnosis of tuberculosis was confirmed by a microscopic examination of a sputum smear, a sputum culture and an X-ray examination. Sensitivity results were available in 1681 patients. In 72.1% of cases, the pathogen was sensitive to all drugs, in 10.1% it was resistant to streptomycin (these patients were group 1), in 10.7% it was resistant to isoniazid, but was susceptible to rifampicin, 2.0% - resistant to rifampicin, but sensitive to isoniazid (group 2) and 4.2% - resistant to both drugs (multiple resistance, group 3).
Healing occurred in 81% of patients in the 1st group, 69% - in the 2nd and 36.6% - in the 3rd group of patients. The differences of this indicator in the three groups were statistically significant (criterion X 2, p less than 0.0001).
Treatment failure was observed in 99 patients. In 73 of them, the results of initial and repeated studies of the pathogen's sensitivity to anti-tuberculosis drugs were available. Acquired resistance was defined as resistance to the drug, which was not detected before treatment, but was detected after its completion. In group 1 (n = 31), acquired resistance was detected in 58.1% of patients, multiple resistance acquired in 41.9%. In group 2 (n = 24), these indicators were 79.2% and 70.8% respectively.
The study limitation was the inability to exclude reinfection during treatment and infection with multiple strains that could affect the results of the sensitivity determination. Imperfect laboratory methods for determining sensitivity could also affect the results.
Thus, a significant effect of the primary resistance of M. tuberculosis on the effectiveness of the standard course of short-term chemotherapy was revealed. All patients who did not respond to short-term chemotherapy had an increased risk of the development of multiple acquired resistance in the pathogen. This risk is highest with initial resistance from M. tuberculosis. Thus, multiple acquired resistance formed in an initially resistant (but not multidrug resistant) strain after unsuccessful treatment in 70.8% of cases. It is important to note that the formation of multiple resistances occurred in 41.9% of the strains that were initially sensitive to all drugs.
Early detection of drug-resistant TB and the reasonable use of reserve drugs can reduce the spread of resistant strains and prevent the formation of multiple resistances.

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