Journal
LANCET
Volume 380, Issue 9851, Pages 1406-1417Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0140-6736(12)60734-X
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Funding
- US Agency for International Development
- Centers for Disease Control and Prevention
- National Institutes of Health/National Institute of Allergy and Infectious Diseases
- Korean Ministry of Health and Welfare
- Centers for Disease Control and Prevention Division of Tuberculosis Elimination
- National Institute of Allergy and Infectious Diseases
- North Estonia Regional Hospital
- Tartu University Hospital, Estonia National Tuberculosis Registry
- Estonia National Institute for Health Development
- State Agency Infectology Centre of Latvia
- Riga Tuberculosis and Lung Disease Clinic
- Lima Ciudad and Lima Este Health Districts and reference laboratories
- Philippines Tropical Disease Foundation
- Orel and Vladimir Oblast Tuberculosis Dispensaries
- Central Tuberculosis Research Institute of the Russian Academy of Medical Sciences
- South Africa Medical Research Council
- KwaZulu-Natal King George V Hospital
- Klerksdorp Hospital
- Witbank Specialised Tuberculosis Hospital
- Jose Pearson Hospital
- Korean Institute of Tuberculosis
- National Masan Tuberculosis Hospital
- Thai Office of Disease Prevention and Control
- WHO in Switzerland, Denmark, Peru, and Russia
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Background The prevalence of extensively drug-resistant (XDR) tuberculosis is increasing due to the expanded use of second-line drugs in people with multidrug-resistant (MDR) disease. We prospectively assessed resistance to second-line antituberculosis drugs in eight countries. Methods From Jan 1, 2005, to Dec 31, 2008, we enrolled consecutive adults with locally confirmed pulmonary MDR tuberculosis at the start of second-line treatment in Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea, and Thailand. Drug-susceptibility testing for study purposes was done centrally at the Centers for Disease Control and Prevention for 11 first-line and second-line drugs. We compared the results with clinical and epidemiological data to identify risk factors for resistance to second-line drugs and XDR tuberculosis. Findings Among 1278 patients, 43.7% showed resistance to at least one second-line drug, 20.0% to at least one second-line injectable drug, and 12.9% to at least one fluoroquinolone. 6.7% of patients had XDR tuberculosis (range across study sites 0.8-15.2%). Previous treatment with second-line drugs was consistently the strongest risk factor for resistance to these drugs, which increased the risk of XDR tuberculosis by more than four times. Fluoroquinolone resistance and XDR tuberculosis were more frequent in women than in men. Unemployment, alcohol abuse, and smoking were associated with resistance to second-line injectable drugs across countries. Other risk factors differed between drugs and countries. Interpretation Previous treatment with second-line drugs is a strong, consistent risk factor for resistance to these drugs, including XDR tuberculosis. Representative drug-susceptibility results could guide in-country policies for laboratory capacity and diagnostic strategies.
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