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Influence of Multidrug Resistance on Tuberculosis Treatment Outcomes with Standardized Regimens

¹ Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, Canada; ² Global Drug Facility, World Health Organization, Geneva, Switzerland; ³ Pan American Health Organization, Washington, DC; ⁴ European Regional Office, World Health Organization, Copenhagen, Denmark; and ⁵ South-East Asian Regional Office, World Health Organization, New Delhi, India

Correspondence and requests for reprints should be addressed to Dick Menzies, M.D., Montreal Chest Institute, Room K1.24, 3650 St. Urbain, Montreal, PQ, Canada H2X 2P4. E-mail: dick.menzies{at}mcgill.ca

Rationale: Multidrug-resistant tuberculosis (TB) poses a major challenge to global TB control. We analyzed the association between estimated prevalence of initial or acquired MDR-TB, and treatment outcomes reported nationally.

Objectives: We analyzed the estimated prevalence of initial or acquired MDR-TB and treatment outcomes reported nationally.

Methods: Countries were analyzed if multidrug resistance prevalence estimates were available, and if they reported outcomes for more than 250 cases treated using standardized regimens in 2003 and/or 2004. Data sources were the World Health Organization for treatment regimens, prevalence of initial multidrug resistance, and reported cases and treatment outcomes in 2003 and 2004; the Joint United Nations Programme on HIV/AIDS for HIV seroprevalence; and the World Bank for income per capita. The adjusted impact of initial multidrug resistance on initial and retreatment outcomes was estimated with weighted multivariate linear regression.

Measurements and Main Results: Among countries using one of two standardized initial regimens, failure rates averaged 5.0%, and relapse rates averaged 12.8% in the 20 countries where prevalence of initial multidrug resistance exceeded 3%, compared with an average of 1.6% (P < 0.0001) and 8.1% (P = 0.0002), respectively, in 83 countries where initial multidrug resistance prevalence was less than 3%. In 92 countries using one standardized retreatment regimen, failure rates were 2.7%, 3.8%, 6.2%, and 8.1% in quartiles of increasing prevalence of acquired multidrug resistance (P < 0.0001). When stratified by initial multidrug resistance prevalence, initial and retreatment outcomes in the 79 countries using the 6-month rifampin initial regimen were not significantly different from the 24 countries using the 2-month rifampin initial regimen.

Conclusions: Currently recommended standardized TB initial and retreatment regimens should be reevaluated in countries where prevalence of initial multidrug resistance exceeds 3%, in view of poor treatment outcomes.

Key Words: tuberculosis • tuberculosis treatment • drug resistance • multidrug resistance • treatment outcomes

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Multidrug-resistant tuberculosis poses an increasing challenge to tuberculosis control worldwide. In countries where drug sensitivity testing is not performed routinely, the current standardized regimens may be contributing to worsening drug resistance levels. What This Study Adds to the Field In 103 countries where standardized treatment regimens are used, failure and relapse rates were significantly higher if the initial multidrug resistance prevalence was 3% or higher. In these countries, more than 20% of all patients on treatment required retreatment.

 

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