Improving outcomes for multidrug-resistant tuberculosis: aggressive regimens prevent treatment failure and death.

BACKGROUND: Evidence is sparse regarding the optimal construction of regimens to treat multidrug-resistant (MDR) tuberculosis disease due to strains of Mycobacterium tuberculosis resistant to at least both isoniazid and rifampin. Given the low potency of many second-line antituberculous drugs, we hypothesized that an aggressive regimen of at least 5 likely effective drugs during the intensive phase, including a fluoroquinolone and a parenteral agent, would be associated with a reduced risk of death or treatment failure. METHODS: We conducted a retrospective cohort study of patients initiating MDR tuberculosis treatment between 2000 and 2004 in Tomsk, Russian Federation. We used a multivariate Cox proportional hazards model to assess whether monthly exposure to an aggressive regimen was associated with the risk of death or treatment failure. RESULTS: Six hundred fourteen individuals with confirmed MDR tuberculosis were eligible for analysis. On multivariable analysis that adjusted for extensively drug-resistant (XDR) tuberculosis-MDR tuberculosis isolates resistant to fluoroquinolones and parenteral agents-we found that monthly exposure to an aggressive regimen was significantly associated with a lower risk of death or treatment failure (hazard ratio, 0.52 [95% confidence interval, .29-.94]; P = .030). CONCLUSIONS: Receipt of an aggressive treatment regimen was a robust predictor of decreased risk of death or failure during MDR tuberculosis treatment. These findings further support the use of this regimen definition as the benchmark for the standard of care of MDR tuberculosis patients and should be used as the basis for evaluating novel therapies.

Performance of the alcohol use disorders identification test among tuberculosis patients in Russia.

The alcohol use disorders identification test (AUDIT), a screening instrument to identify individuals at risk of alcohol use-related problems, has not been validated in a Russian primary care population. We assessed the reliability, factor structure, sensitivity, and specificity of AUDIT scores among 254 subjects initiating tuberculosis treatment from 2005 to 2007 in Tomsk City. Our findings support the use of the AUDIT as a screening instrument among Russian individuals seeking primary care. We discuss implications, limitations, and future research.

Alcohol consumption among men and women with tuberculosis in Tomsk, Russia.

Drinking behavior among Russian women remains poorly described. We analyzed gender differences in alcohol use among 374 tuberculosis patients in Tomsk, Siberia. Twenty-six (28.3%) women had lifetime alcohol abuse or dependence, compared with 70.6% of men. Women with alcohol use disorders drank 12.7 +/- 14.0 standard drinks per day and > or = 34.6% drank 2 three days per week. Among individuals with a lifetime alcohol use disorder, age of onset and typical consumption did not differ significantly by gender. We conclude that Russian women with alcohol use disorders consume almost as much alcohol as men and may be at greater risk for negative social and medical consequences.

Integration of alcohol use disorders identification and management in the tuberculosis programme in Tomsk Oblast, Russia.

Alcohol use disorders (AUDs) among tuberculosis (TB) patients are associated with nonadherence and poor treatment outcomes. We developed a multidisciplinary model to manage AUDs among TB patients in Tomsk, Russia. First, we assessed current standards of care through stakeholder meetings and ethnographic work. The Alcohol Use Disorders Identification Test (AUDIT) was incorporated into routine assessment of all patients starting TB treatment. We established treatment algorithms based on AUDIT scores. We then hired specialists and addressed licensing requirements to provide on-site addictions care. Our experience offers a successful model in the management of co-occurring AUDs among patients with chronic medical problems.

Knowledge, attitudes, and practices of physicians in Tomsk Oblast tuberculosis services regarding alcohol use among tuberculosis patients in Tomsk, Russia.

In recent years, the Russian Federation has seen a dramatic rise in morbidity and mortality from tuberculosis (TB), attributed in part to an increase in alcohol use disorders (AUDs), which are associated with worse TB treatment outcomes. This study describes the knowledge, attitudes and practices of physicians who treat TB patients in Tomsk, Russia. We conducted semistructured interviews with 16 TB physicians and 1 addiction specialist. Interviews were audiorecorded, transcribed, translated and systematically analyzed. We identified four key domains: definitions of alcohol use and abuse and physicians' knowledge, attitudes and practices regarding these problems. Physicians described patients as largely precontemplative and reluctant to seek treatment. Physicians recognized their limited knowledge in diagnosing and treating AUDs but expressed interest in acquiring these skills. Few options are currently available for treatment of AUDs in TB patients in Tomsk. These findings suggest that Tomsk physicians are aware of the need to engage AUDs in TB patients but identify a knowledge gap that restricts their ability to do so. Training TB physicians to use simple screening instruments and deliver evidence-based alcohol interventions improves TB outcomes among patients with co-occurring AUDs.

Understanding HIV Risk Behavior among Tuberculosis Patients with Alcohol Use Disorders in Tomsk, Russian Federation.

Russian Federation's (RF) HIV epidemic is the fastest growing of any country. This study explores factors associated with high HIV risk behavior in tuberculosis (TB) patients with alcohol use disorders in Tomsk, RF. This analysis was nested within the Integrated Management of Physician-delivered Alcohol Care for TB Patients (IMPACT, trial number NCT00675961) randomized controlled study of integrating alcohol treatment into TB treatment in Tomsk. Demographics, HIV risk behavior (defined as participant report of high-risk intravenous drug use and/or multiple sexual partners with inconsistent condom use in the last six months), clinical data, alcohol use, depression and psychosocial factors were collected from 196 participants (161 male and 35 female) at baseline. Forty-six participants (23.5%) endorsed HIV risk behavior at baseline. Incarceration history(Odds Ratio (OR)3.93, 95% confidence interval (CI) 1.95, 7.95), age under 41 (OR:2.97, CI:1.46, 6.04), drug addiction(OR: 3.60 CI:1.10, 11.77), history of a sexually transmitted disease(STD)(OR 2.00 CI:1.02, 3.90), low social capital (OR:2.81 CI:0.99, 8.03) and heavier alcohol use (OR:2.56 CI: 1.02, 6.46) were significantly more likely to be associated with HIV risk behavior at baseline. In adjusted analysis, age under 41(OR: 4.93, CI: 2.10, 11.58), incarceration history(OR: 3.56 CI:1.55, 8.17) and STD history (OR: 3.48, CI: 1.5, 8.10) continued to be significantly associated with HIV risk behavior. Understanding HIV transmission dynamics in Russia remains an urgent priority to inform strategies to address the epidemic. Larger studies addressing sex differences in risks and barriers to protective behavior are needed.

The effect of initial drug resistance on treatment response and acquired drug resistance during standardized short-course chemotherapy for tuberculosis.

BACKGROUND: In Tomsk Oblast, Russian Federation, during the period of 1996-2000, most previously untreated patients with tuberculosis received standardized short-course chemotherapy, irrespective of drug-susceptibility testing results. A retrospective analysis was done to determine the effect of initial drug resistance on treatment outcome and acquired drug resistance in new patients receiving standardized short-course chemotherapy. METHODS: During the period of 1 November 1996 through 31 December 2000, a total of 2194 patients received a category 1 treatment regimen. Drug susceptibility test results for 1681 patients were available for analysis. Drug resistance patterns before and during treatment were compared for 73 patients whose culture results were persistently positive during treatment. Acquired resistance was defined as new drug resistance (during or at the end of treatment) that was not present at the beginning of treatment. RESULTS: Pretreatment drug resistance was strongly associated with treatment failure. In patients who had strains with pretreatment resistance patterns that included isoniazid or rifampin resistance, but not resistance to both, 17 (70.8%) of 24 cases involving treatment failures acquired new multidrug resistance. In patients with pretreatment pan-susceptible or streptomycin-monoresistant strains, 13 (41.9%) of 31 cases involving treatment failures acquired new multidrug resistance. CONCLUSIONS: Early diagnosis of drug-resistant tuberculosis and judicious use of second-line drugs is recommended to decrease transmission of drug-resistant strains and to prevent the creation of multidrug-resistant strains. Finally, if drug susceptibility tests are not available or results are delayed, physicians should recognize that patients who do not respond to directly observed empirical short-course chemotherapy are at high risk of having multidrug-resistant tuberculosis and should be treated accordingly.

Effectiveness of alcohol treatment interventions integrated into routine tuberculosis care in Tomsk, Russia.

AIMS: To test the feasibility and effectiveness of brief counseling intervention (BCI) and naltrexone integrated into tuberculosis (TB) care in Tomsk, Russia. DESIGN: Using a factorial randomized controlled trial design, patients were randomized into: naltrexone (NTX), brief behavioral compliance enhancement therapy (BBCET), treatment as usual (TAU) and BCI. SETTING AND PARTICIPANTS: In the Tomsk Oblast, hospitalized TB patients diagnosed with alcohol use disorders (AUDs) by the DSM-IV were referred at the start of TB treatment. Of the 196 participants, the mean age was 41 years and 82% were male. Severe TB (84.7% had cavitary disease) and smoking (92.9%) were common. The majority had a diagnosis of an AUD (63.0%); 27.6% reported nearly daily drinking and consumed a median of 16 standard drinks per day. MEASUREMENTS: Primary outcomes were 'favorable' TB outcome (cured, completed treatment) and change in mean number of abstinent days in the last month of study compared with baseline. Change in mean number of heavy drinking days, defined as four drinks per day and five drinks per day for women and men, respectively, and TB adherence, measured as percentage of doses taken as prescribed under direct observation, were secondary outcomes. Analysis based on 'intention-to-treat' was performed for multivariable analysis. FINDINGS: Primary TB and alcohol end-points between naltrexone and no-naltrexone or BCI and no-BCI groups did not differ significantly. TB treatment adherence and change in number of heavy drinking days also did not differ significantly among treatment arms. Among individuals with a prior quitting attempt (n = 111), naltrexone use was associated with an increased likelihood of favorable TB outcomes (92.3% versus 75.9%, P = 0.02). CONCLUSIONS: In Tomsk Oblast, Russia, tuberculosis patients with severe alcohol use disorders who were not seeking alcohol treatment did not respond to naltrexone or behavioral counselling integrated into tuberculosis care; however, those patients with past attempts to quit drinking had improved tuberculosis outcomes.

Implementing evidence-based alcohol interventions in a resource-limited setting: novel delivery strategies in Tomsk, Russia.

Effective implementation of evidence-based interventions in "real-world" settings can be challenging. Interventions based on externally valid trial findings can be even more difficult to apply in resource-limited settings, given marked differences-in provider experience, patient population, and health systems-between those settings and the typical clinical trial environment. Under the auspices of the Integrated Management of Physician-Delivered Alcohol Care for Tuberculosis Patients (IMPACT) study, a randomized, controlled effectiveness trial, and as an integrated component of tuberculosis treatment in Tomsk, Russia, we adapted two proven alcohol interventions to the delivery of care to 200 patients with alcohol use disorders. Tuberculosis providers performed screening for alcohol use disorders and also delivered naltrexone (with medical management) or a brief counseling intervention either independently or in combination as a seamless part of routine care. We report the innovations and challenges to intervention design, training, and delivery of both pharmacologic and behavioral alcohol interventions within programmatic tuberculosis treatment services. We also discuss the implications of these lessons learned within the context of meeting the challenge of providing evidence-based care in resource-limited settings.