The Lancet, Volume 380, Issue 9851, Pages 1406 - 1417, 20 October 2012

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

 Dr Tracy Dalton PhD , Peter Cegielski MD, Somsak Akksilp MD, Luis Asencios MPH, Janice Campos Caoili MD, Prof Sang-Nae Cho PhD, Vladislav V Erokhin MD, Julia Ershova PhD, Ma Tarcela Gler MD, Boris Y Kazennyy MD, Hee Jin Kim MD, Kai Kliiman MD, Ekaterina Kurbatova MD, Charlotte Kvasnovsky MD, Vaira Leimane MD, Martie van der Walt PhD, Laura E Via PhD, Grigory V Volchenkov MD, Martin A Yagui MD, Hyungseok Kang MD

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.