Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis.
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Cegielski J Peter, Dalton Tracy, Yagui Martin, Wattanaamornkiet Wanpen, Volchenkov Grigory V, Via Laura E, Van Der Walt Martie, Tupasi Thelma, Smith Sarah E, Odendaal Ronel, Leimane Vaira, Kvasnovsky Charlotte, Kuznetsova Tatiana, Kurbatova Ekaterina, Kummik Tiina, Kuksa Liga, Kliiman Kai, Kiryanova Elena V, Kim HeeJin, Kim Chang-ki, Kazennyy Boris Y, Jou Ruwen, Huang Wei-Lun, Ershova Julia, Erokhin Vladislav V, Diem Lois, Contreras Carmen, Cho Sang Nae, Chernousova Larisa N, Chen Michael P, Caoili Janice Campos, Bayona Jaime, Akksilp Somsak, Global Preserving Effective TB Treatment Study (PETTS) Investigators
Аннотация
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.