Risk of further resistance to TB drugs rose with ongoing treatment of multidrug-resistant (MDR) TB, according to results of a 9-country analysis. Risk of further resistance was about 75% to 80% lower in countries that met international Green Light Committee (GLC) criteria.
MDR-TB and extensively drug-resistant (XDR) TB are growing threats in countries with high TB prevalence. HIV-positive people account for many cases of MDR-TB and XDR-TB. In 2000 the international GLC initiative began trying to increase access to drugs for treatment of MDR-TB while limiting development of further resistance (click GLC on link below).
To determine the impact of GLC, researchers monitored adults with pulmonary TB from the start to the end of treatment in 9 countries—5 countries that met GLC criteria and 4 that did not. Study participants had monthly sputum cultures, drug susceptibility testing, and genotyping. The research team compared frequency and predictors of acquired resistance to second-line TB drugs in the GLC countries and the non-GLC countries.
The analysis involved 832 adults. Among those without initial resistance to specific second-line TB drugs, 68 (8.9%) acquired XDR-TB, 79 (11.2%) acquired fluoroquinolone resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs.
Relative risk (RR) for acquired resistance was significantly lower in GLC-approved sites for XDR-TB (RR 0.27, 95% confidence interval [CI] 0.16 to 0.47), for fluoroquinolone (RR 0.28, 95% CI 0.17 to 0.45), and for three different second-line injectable drugs (RR 0.15, 95% CI 0.06 to 0.39).
Risk of acquiring resistance to second-line TB drugs rose as the number of potentially effective drugs fell. Statistical analysis that controlled for initial drug resistance and differences between study sites found that people treated at GLC sites had about 80% lower odds of acquired XDR-TB (odds ratio 0.21, 95% CI 0.07 to 0.62) and acquired fluoroquinolone resistance (OR 0.23, 95% CI 0.09 to 0.59).
“Treatment of MDR tuberculosis involves substantial risk of acquired resistance to second-line drugs,” the authors conclude, “increasing as baseline drug resistance increases.” But the risk of additional second-line resistance was significantly lower in programs that met GLC standards.
Source: 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, for the Global Preserving Effective TB Treatment Study (PETTS) Investigators. Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis. Clinical Infectious Diseases. 2014; 59: 1064-1065.
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For an editorial on this study