Influence of multidrug resistance on tuberculosis treatment outcomes with standardized regimens.
BACKGROUND
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.


OBJECTIVE
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.


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.
Mak
Anton
A
Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, Canada.
Thomas
Adam
A
Del Granado
Mirtha
M
Zaleskis
Richard
R
Mouzafarova
Nigor
N
Menzies
Dick
D
D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D002985:Clinical Protocols; D004359:Drug Therapy, Combination; D014943:Global Health; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D017410:Practice Guidelines as Topic; D055502:Secondary Prevention; D017211:Treatment Failure; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy*
D000904:Antibiotics, Antitubercular