Hepatotoxicity during treatment for multidrug-resistant tuberculosis: occurrence, management and outcome.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) treatment program in Tomsk, Russia. OBJECTIVE: To describe the incidence and management of hepatotoxicity during treatment of MDR-TB, and to assess risk factors associated with its development and impact on treatment outcomes. DESIGN: A retrospective case series performed among 608 patients. RESULTS: Hepatotoxicity, using American Thoracic Society (2006) definitions, was observed in 91/568 patients (16.5%). The median time to the first hepatotoxic event was 196 days post treatment commencement. Baseline factors associated with hepatotoxicity included elevated alanine aminotransferase/aspartate aminotransferase/bilirubin (OR 53.9, 95%CI 6.30-438.7), and renal insufficiency (OR 19.6, 95%CI 2.71-141.6). High treatment adherence (OR 3.25, 95%CI 2.07-5.09) and starting treatment in prison (OR 1.77, 95%CI 1.04-3.01) were associated with treatment success. Smoking (OR 0.44, 95%CI 0.21-0.92) and bilateral cavitary disease (OR 0.51, 95%CI 0.34-0.77) were associated with worse outcomes. For alcohol users, developing hepatotoxicity was associated with better outcomes (OR 4.40, 95%CI 1.79-10.81) than not (OR 0.42, 95%CI 0.25-0.68). One or more medications were permanently stopped in 10/91 patients, but in no case was treatment entirely discontinued. CONCLUSION: MDR-TB treatment in the face of hepatotoxicity during therapy did not result in a statistically significant increase in poor outcomes.

'Sputnik': a programmatic approach to improve tuberculosis treatment adherence and outcome among defaulters.

SETTING: A novel patient-centered tuberculosis (TB) treatment delivery program, 'Sputnik', was introduced for patients at high risk of treatment default in Tomsk City, Russian Federation. OBJECTIVE: To assess the effects of the Sputnik intervention on patient default rates. DESIGN: We analyzed the characteristics of patients referred to the program, treatment adherence of Sputnik program enrollees before and during the intervention, and final outcomes for all patients referred to the Sputnik program. RESULTS: For patients continuing their existing regimens after referral to the program (n = 46), mean adherence to treatment increased by 56% (from 52% of prescribed doses prior to enrolment to 81%). For patients initiating new regimens after referral ( n = 5), mean adherence was 83%. Mean adherence for patients with multidrug-resistant TB (MDR-TB; n = 38) was 79% and for all others (n = 13) it was 89%. The cure rate was 71.1% for patients with MDR-TB, 60% for all others and 68% in the program overall. CONCLUSION: The Sputnik intervention was successful in reducing rates of treatment default among patients at high risk for non-adherence.

Treating multidrug-resistant tuberculosis in Tomsk, Russia: developing programs that address the linkage between poverty and disease.

Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) are diseases of poverty. Because Mycobacterium tuberculosis exists predominantly in a social space often defined by poverty and its comorbidities--overcrowded or congregate living conditions, substance dependence or abuse, and lack of access to proper health services, to name a few--the biology of this organism and of TB drug resistance is intimately linked to the social world in which patients live. This association is demonstrated in Russia, where political changes in the 1990s resulted in increased socioeconomic inequality and a breakdown in health services. The effect on TB and MDR-TB is reflected both in terms of a rise in TB and MDR-TB incidence and increased morbidity and mortality associated with the disease. We present the case example of Tomsk Oblast to delineate how poverty contributed to a growing MDR-TB epidemic and increasing socioeconomic barriers to successful care, even when available. The MDR-TB pilot project implemented in Tomsk addressed both programmatic and socioeconomic factors associated with unfavorable outcomes. The result has been a strengthening of the overall TB control program in the region and improved case-holding for the most vulnerable patients. The model of MDR-TB care in Tomsk is applicable for other resource-poor settings facing challenges to TB and MDR-TB control.