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Multicenter Study
. 2012 Oct 20;380(9851):1406-17.
doi: 10.1016/S0140-6736(12)60734-X. Epub 2012 Aug 30.

Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study

Tracy Dalton  1 , Peter Cegielski, Somsak Akksilp, Luis Asencios, Janice Campos Caoili, Sang-Nae Cho, Vladislav V Erokhin, Julia Ershova, Ma Tarcela Gler, Boris Y Kazennyy, Hee Jin Kim, Kai Kliiman, Ekaterina Kurbatova, Charlotte Kvasnovsky, Vaira Leimane, Martie van der Walt, Laura E Via, Grigory V Volchenkov, Martin A Yagui, Hyungseok Kang; Global PETTS Investigators; Rattanawadee Akksilp, Wanlaya Sitti, Wanpen Wattanaamornkiet, Sofia N Andreevskaya, Larisa N Chernousova, Olga V Demikhova, Elena E Larionova, Tatyana G Smirnova, Irina A Vasilieva, Alena V Vorobyeva, Clifton E Barry 3rd, Ying Cai, Isdore C Shamputa, Jaime Bayona, Carmen Contreras, Cesar Bonilla, Oswaldo Jave, Jeannette Brand, Joey Lancaster, Ronel Odendaal, Michael P Chen, Lois Diem, Beverly Metchock, Kathrine Tan, Allison Taylor, Melanie Wolfgang, Eunjin Cho, Seok Yong Eum, Hyun Kyung Kwak, Jiim Lee, Jongseok Lee, Seonyeong Min, Irina Degtyareva, Evgenia S Nemtsova, Tatiana Khorosheva, Elena V Kyryanova, Grace Egos, Ma Therese C Perez, Thelma Tupasi, Soo Hee Hwang, Chang-ki Kim, Su Young Kim, Hee Jeong Lee, Liga Kuksa, Inga Norvaisha, Girts Skenders, Ingrida Sture, Tiina Kummik, Tatiana Kuznetsova, Tatiana Somova, Klavdia Levina, Gustavo Pariona, Gloria Yale, Carmen Suarez, Eddy Valencia, Piret Viiklepp
Collaborators, Affiliations
Multicenter Study

Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study

Tracy Dalton et al. Lancet. .

Erratum in

  • Lancet. 2012 Oct 20;380(9851):1386

Abstract

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.

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Conflict of interest statement

Conflicts of interest

We declare that we have no conflicts of interest.

Figures

Figure:
Figure:. Study profile
CDC=Centers for Disease Control and Prevention. MDR=multidrug-resistant. *All from Taiwan.
See this image and copyright information in PMC

Comment in

References

    1. Wright A, Zignol M, Van Deun A, et al. Epidemiology of antituberculosis drug resistance 2002–07: an updated analysis of the Global Project on Anti-Tuberculosis Drug Resistance Surveillance. Lancet 2009; 373: 1861–73. - PubMed
    1. WHO. Multidrug and extensively drug-resistant TB (M/XDR-TB). 2010 Global Report on Surveillance and response. Geneva:World Health Organization, 2010.
    1. GLC Program applications. http://www.who.int/tb/challenges/mdr/greenlightcommittee/report_glc_appl... (accessed June 1, 2012).
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    1. Shah NS, Wright A, Bai G-H, et al. Worldwide emergence of extensively drug-resistant tuberculosis. Emerg Infect Dis 2007; 13: 380–87. - PMC - PubMed

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