Published ahead of print on May 29, 2008, doi:10.1164/rccm.200802-240OC Am. J. Respir. Crit. Care Med., Volume 178, Number 3, August 2008, 306-312 A more recent version of this article appeared on August 1, 2008
Submitted on February 8, 2008 Influence of Multidrug resistance on Tuberculosis Treatment Outcomes with Standardized RegimensAnton Mak1,1 Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, Quebec, Canada, 2 Global Drug Facility, World Health Organization, Geneva, Switzerland, 3 Pan American Health Organization (PAHO), Washington, DC, USA, 4 European Regional Office, World Health Organization, Copenhagen, Denmark, 5 South-East Asian Regional Office, World Health Organization, New Delhi, India * To whom correspondence should be addressed. E-mail: dick.menzies{at}mcgill.ca.
Background: Multidrug-resistant (MDR) tuberculosis poses a major challenge to global tuberculosis control. We analyzed the association between estimated prevalence of initial or acquired MDR tuberculosis, and treatment outcomes reported nationally. Methods: Countries were analyzed if MDR prevalence estimates were available, and they reported outcomes for more than 250 cases treated using standardized regimens in 2003, and/or 2004. Data sources were: World Health Organization for treatment regimens, prevalence of initial MDR, and reported cases and treatment outcomes in 2003 and 2004, UNAIDS for HIV sero-prevalence, and the World Bank for income per capita. The adjusted impact of initial MDR on initial and retreatment outcomes was estimated with weighted multivariate linear regression. 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 MDR exceeded 3%, compared to an average of 1.6% (p<0.0001), and 8.1% (p=0.0002) respectively, in 83 countries where initial MDR 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 MDR (p<0.0001). When stratified by initial MDR prevalence, initial and re-treatment 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. Conclusion: Currently recommended standardized tuberculosis initial and re-treatment regimens should be re-evaluated in countries where prevalence of initial multi-drug resistance exceeds 3%, in view of poor treatment outcomes. Key words: Tuberculosis, tuberculosis treatment, Drug resistance, Multidrug resistance, Treatment outcomes
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