Standard short-course chemotherapy for drug-resistant tuberculosis - Treatment outcomes in 6 countries

Context No large-scale study has investigated the impact of multidrug-resis tant tuberculosis (TB) on the outcome of standard short-course chemotherapy under routine countrywide TB control program conditions in the World Healt h Organization's (WHO) directly observed treatment short-course strategy fo r TB control. Objective To assess the results of treatment with first-line drugs for pati ents enrolled in the WHO and the International Union Against Tuberculosis a nd Lung Disease's global project on drug-resistance surveillance. Design and Setting Retrospective cohort study of patients with TB in the Do minican Republic, Hong Kong Special Administrative Region (People's Republi c of China), Italy, Ivanovo Oblast (Russian Federation), the Republic of Ko rea, and Peru. Patients New and retreatment TB cases who received short-course chemotherap y with isoniazid, rifampicin, pyrazinamide, and either ethambutol or strept omycin between 1994 and 1996. Main Outcome Measure Treatment response according to WHO treatment outcome categories (cured; died; completed, defaulted, or failed treatment; or tran sferred). Results Of the 6402 culture-positive TB cases evaluated, 5526 (86%) were ne w cases and 876 (14%) were retreatment cases. A total of 1148 (20.8%) new c ases and 390 (44.5%) retreatment cases were drug resistant, including 184 a nd 169 cases of multidrug-resistant TB, respectively. Of the new cases 4585 (83%) were treated successfully, 138 (2%) died, and 151 (3%) experienced s hort-course chemotherapy failure. Overall, treatment failure (relative risk [RR], 15.4; 95% confidence interval [CI], 10.6-22.4; P<.001) and mortality (RR, 3.73; 95% CI, 2.13-6.53; P<.001) were higher among new multidrug-resi stant TB cases than among new susceptible cases. Even in settings using 100 % direct observation, cases with multidrug resistance had a significantly h igher failure rate than those who were susceptible (9/94 [10%] vs 8/1410 [0 .7%1; RR, 16.9; 95% CI, 6.6-42.7; P<.001). Treatment failure was also highe r among patients with any rifampicin resistance (n = 115) other than multid rug resistance (RR, 5.48, 95% CI, 3.04-9.87; P<.001), any isoniazid resista nce (n = 457) other than multidrug resistance (RR, 3.06; 95% CI, 1.85-5.05; P<.001), and among patients with TB resistant to rifampicin only (n = 76) (RR, 5.47; 95% CI, 2.68-11.2; P<,001). Of the retreatment cases, 497 (57%) were treated successfully, 51 (6%) died, and 124 (14%) failed short-course chemotherapy treatment. Failure rates among retreatment cases were higher i n those with muitidrug-resistant TB, with any isoniazid resistance other th an multidrug resistance, and in cases with TB resistant to isoniazid only. Conclusions These data suggest that standard short-course chemotherapy, bas ed on first-line drugs, is an inadequate treatment for some patients with d rug-resistant TB. Although the directly observed treatment short-course str ategy is the basis of good TB control, the strategy should be modified in s ome settings to identify drug-resistant cases sooner, and to make use of se cond-line drugs in appropriate treatment regimens.