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The Lancet. Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study
[Source: The Lancet, full page: (LINK). Abstract, edited.]
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The Lancet, Early Online Publication, 30 August 2012
doi:10.1016/S0140-6736(12)60734-X
Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study
Original Text
Dr Tracy Dalton PhD a, Peter Cegielski MD a, Somsak Akksilp MD b, Luis Asencios MPH c, Janice Campos Caoili MD d, Prof Sang-Nae Cho PhD e, Vladislav V Erokhin MD f, Julia Ershova PhD a, Ma Tarcela Gler MD d, Boris Y Kazennyy MD g, Hee Jin Kim MD h, Kai Kliiman MD i, Ekaterina Kurbatova MD a, Charlotte Kvasnovsky MD a, Vaira Leimane MD j, Martie van der Walt PhD k, Laura E Via PhD l, Grigory V Volchenkov MD m, Martin A Yagui MD n, Hyungseok Kang MD o, the Global PETTS Investigators?
Summary
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.
Funding
US Agency for International Development, Centers for Disease Control and Prevention, National Institutes of Health/National Institute of Allergy and Infectious Diseases, and Korean Ministry of Health and Welfare.
a Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, GA, USA; b Office of Disease Prevention and Control Region 7, Ubon Ratchatani, Thailand; c National Tuberculosis Reference Laboratory, Lima, Peru; d Tropical Disease Foundation, Manila, Philippines; e International Tuberculosis Research Center, Masan and Yonsei University College of Medicine, Seoul, South Korea; f Central Tuberculosis Research Institute, Russian Academy of Medical Sciences, Moscow, Russian Federation; g Orel Oblast Tuberculosis Dispensary, Orel, Russian Federation; h Korean Institute of Tuberculosis, Seoul, South Korea; i Tartu University Hospital, Tartu, Estonia; j State Agency, Infectology Centre of Latvia, Tuberculosis and Lung Disease Clinic, Riga, Latvia; k Medical Research Council, Pretoria, South Africa; l National Institute for Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA; m Vladimir Oblast Tuberculosis Dispensary, Vladimir, Russian Federation; n National Institute of Health, Lima, Peru; o National Masan Tuberculosis Hospital, Masan, South Korea
Correspondence to: Dr Tracy Dalton, Centers for Disease Control and Prevention, 1600 Clifton Road Northeast, Mailstop F08, Atlanta, GA 30333, USA
? Continued at end of article.
-doi:10.1016/S0140-6736(12)60734-X
Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study
Original Text
Dr Tracy Dalton PhD a, Peter Cegielski MD a, Somsak Akksilp MD b, Luis Asencios MPH c, Janice Campos Caoili MD d, Prof Sang-Nae Cho PhD e, Vladislav V Erokhin MD f, Julia Ershova PhD a, Ma Tarcela Gler MD d, Boris Y Kazennyy MD g, Hee Jin Kim MD h, Kai Kliiman MD i, Ekaterina Kurbatova MD a, Charlotte Kvasnovsky MD a, Vaira Leimane MD j, Martie van der Walt PhD k, Laura E Via PhD l, Grigory V Volchenkov MD m, Martin A Yagui MD n, Hyungseok Kang MD o, the Global PETTS Investigators?
Summary
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.
Funding
US Agency for International Development, Centers for Disease Control and Prevention, National Institutes of Health/National Institute of Allergy and Infectious Diseases, and Korean Ministry of Health and Welfare.
a Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, GA, USA; b Office of Disease Prevention and Control Region 7, Ubon Ratchatani, Thailand; c National Tuberculosis Reference Laboratory, Lima, Peru; d Tropical Disease Foundation, Manila, Philippines; e International Tuberculosis Research Center, Masan and Yonsei University College of Medicine, Seoul, South Korea; f Central Tuberculosis Research Institute, Russian Academy of Medical Sciences, Moscow, Russian Federation; g Orel Oblast Tuberculosis Dispensary, Orel, Russian Federation; h Korean Institute of Tuberculosis, Seoul, South Korea; i Tartu University Hospital, Tartu, Estonia; j State Agency, Infectology Centre of Latvia, Tuberculosis and Lung Disease Clinic, Riga, Latvia; k Medical Research Council, Pretoria, South Africa; l National Institute for Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA; m Vladimir Oblast Tuberculosis Dispensary, Vladimir, Russian Federation; n National Institute of Health, Lima, Peru; o National Masan Tuberculosis Hospital, Masan, South Korea
Correspondence to: Dr Tracy Dalton, Centers for Disease Control and Prevention, 1600 Clifton Road Northeast, Mailstop F08, Atlanta, GA 30333, USA
? Continued at end of article.
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