Alexander D. Pasechnikov

Multidrug-resistant tuberculosis management in resource-limited settings.

Managing MDRTB through national programs can yield results similar to those seen in wealthier settings.

Treatment of extensively drug-resistant tuberculosis in Tomsk, Russia: a retrospective cohort study

BACKGROUND Mycobacterium tuberculosis strains that cause untreatable drug-resistant disease are a threat worldwide. We describe the treatment, management, and outcomes of patients with extensively drug-resistant tuberculosis in Tomsk, Russia. METHODS We undertook a retrospective cohort study of 608 patients with multidrug resistant tuberculosis who had treatment in civilian or prison services, between Sept 10, 2000, and Nov 1, 2004, according to the treatment strategy recommended by WHO. Clinical characteristics, management practices, and treatment outcomes of patients with extensively drug-resistant (XDR) tuberculosis and non-extensively drug-resistant (non-XDR) tuberculosis are described. The main outcome was the frequency of poor and favourable outcomes at the end of treatment. FINDINGS Of 608 patients with multidrug resistant tuberculosis, 29 (4.8%) patients had baseline XDR tuberculosis. Treatment failure was more common in patients with XDR tuberculosis than in those with non-XDR tuberculosis (31%vs 8.5%, p=0.0008). 48.3% of patients with XDR tuberculosis and 66.7% of patients with non-XDR tuberculosis had treatment cure or completion (p=0.04). The frequency and management of adverse events did not differ between patients with XDR and non-XDR tuberculosis. INTERPRETATION The chronic features of tuberculosis in these patients suggest that extensively drug-resistant tuberculosis may be acquired through previous treatments that include second-line drugs. Aggressive management of this infectious disease is feasible and can prevent high mortality rates and further transmission of drug-resistant strains of Mycobacterium tuberculosis.

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.

Development of Extensively Drug-resistant Tuberculosis during Multidrug-resistant Tuberculosis Treatment

RATIONALE Extensively drug-resistant (XDR) tuberculosis (TB) may arise in individuals on treatment for multidrug-resistant (MDR) TB. Preventing this amplification of resistance will likely improve clinical outcomes and delay the secondary spread of XDR-TB. OBJECTIVES To measure the proportion of individuals that develops XDR-TB during the course of MDR-TB treatment, and to identify those factors associated with the development of XDR. METHODS We performed a retrospective analysis of 608 consecutive patients with documented MDR-TB who were started on MDR-TB treatment between September 10, 2000 and November 1, 2004 in the Tomsk Oblast TB Treatment Services in Western Siberia, Russian Federation. MEASUREMENTS AND MAIN RESULTS A total of 6% of patients were observed to develop XDR-TB while on MDR-TB treatment. These patients were significantly less likely to be cured or to complete treatment. Using Cox proportional hazard models, we found that the presence of bilateral and cavitary lesions was associated with a greater than threefold increase in hazard (adjusted hazard ratio [HR], 3.47; 95% confidence interval [CI], 1.32-9.14). Prior exposure to a second-line injectable antibiotic was associated with a greater than threefold increase in hazard (adjusted HR, 3.65; 95% CI, 1.81-7.37), and each additional month in which a patient failed to take at least 80% of their prescribed drugs was associated with nearly an additional 20% hazard of developing XDR-TB (adjusted HR, 1.17; 95% CI, 1.01-1.35). CONCLUSIONS Early and rapid diagnosis, timely initiation of appropriate therapy, and programmatic efforts to optimize treatment adherence during MDR-TB therapy are crucial to avoiding the generation of excess XDR-TB in MDR-TB treatment programs.

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.

New challenges in the clinical management of drug-resistant tuberculosis

Strains of Mycobacterium tuberculosis are multidrug-resistant when isoniazid and rifampin, the two most powerful antituberculous agents, do not inhibit their growth. Only a decade ago, outbreaks of multidrug-resistant tuberculosis (MDR-TB) occurred in New York, California, and Florida. In each setting, early detection by physicians decreased both transmission of and deaths caused by these strains. Working in Haiti, Peru, and Russia, our team has treated over 1,000 patients sick with MDR-TB. Most infecting strains were resistant to all first-line drugs. Because no new antituberculous drugs have been developed in decades, therapeutic options for such patients are limited. Our own experience suggests, however, that prompt detection and effective therapy can cure the great majority of cases of active MDR-TB. We review below the principles of MDR-TB treatment: 18–24 months of therapy with multidrug regimens, designed with use of drug susceptibility testing, and close attention to the management of adverse effects. We also discuss the treatment of MDR-TB in children, during pregnancy, and in the presence of HIV coinfection. Controversies in the management of MDR-TB are reviewed, including the use of resective surgery, the relative efficacy of different fluoroquinolones, and postexposure prophylaxis for close contacts of patients with pulmonary MDR-TB.