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J. Peter Cegielski, Tracy Dalton, Martin Yagui, Wanpen Wattanaamornkiet, Grigory V. Volchenkov, Laura E. Via, Martie Van Der Walt, Thelma Tupasi, Sarah E. Smith, Ronel Odendaal, Vaira Leimane, Charlotte Kvasnovsky, Tatiana Kuznetsova, Ekaterina Kurbatova, Tiina Kummik, Liga Kuksa, Kai Kliiman, Elena V. Kiryanova, HeeJin Kim, Chang-ki Kim, Boris Y. Kazennyy, Ruwen Jou, Wei-Lun Huang, Julia Ershova, Vladislav V. Erokhin, Lois Diem, Carmen Contreras, Sang Nae Cho, Larisa N. Chernousova, Michael P. Chen, Janice Campos Caoili, Jaime Bayona, Somsak Akksilp, Gloria Yale Calahuanca, Melanie Wolfgang, Piret Viiklepp, Irina A. Vasilieva, Allison Taylor, Kathrine Tan, Carmen Suarez, Ingrida Sture, Tatiana Somova, Tatyana G. Smirnova, Erika Sigman, Girts Skenders, Wanlaya Sitti, Isdore C. Shamputa, Vija Riekstina, Kristine Rose Pua, M. Therese, C. Perez, Seungkyu Park, Inga Norvaisha, Evgenia S. Nemtsova, Seonyeong Min, Beverly Metchock, Klavdia Levina, Yung-Chao Lei, Jongseok Lee, Elena E. Larionova, Joey Lancaster, Doosoo Jeon, Oswaldo Jave, Tatiana Khorosheva, Soo Hee Hwang, Angela Song-En Huang, M. Tarcela Gler, Gunta Dravniece, Seokyong Eum, Olga V. Demikhova, Irina Degtyareva, Manfred Danilovits, Anda Cirula, Eunjin Cho, Ying Cai, Jeanette Brand, Cesar Bonilla, Clifton E. Barry, Luis Asencios, Sofia N. Andreevskaya, Rattanawadee Akksilp, for the Global Preserving Effective TB Treatment Study (PETTS) Investigators, Extensive Drug Resistance Acquired During Treatment of Multidrug-Resistant Tuberculosis, Clinical Infectious Diseases, Volume 59, Issue 8, 15 October 2014, Pages 1049–1063, https://doi.org/10.1093/cid/ciu572
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Abstract
Background. Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance.
Methods. To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC.
Results. In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16–.47) for XDR tuberculosis, 0.28 (.17–.45) for FQ, and 0.15 (.06–.39) to 0.60 (.34–1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07–.62) for acquired XDR tuberculosis and 0.23 (.09–.59) for acquired FQ resistance.
Conclusions. Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.
