No large-scale study has investigated the impact of multidrug-resistant
tuberculosis (TB) on the outcome of standard short-course chemotherapy under
routine countrywide TB control program conditions in the World Health Organization's
(WHO) directly observed treatment short-course strategy for TB control.
To assess the results of treatment with first-line drugs for patients
enrolled in the WHO and the International Union Against Tuberculosis and Lung
Disease's global project on drug-resistance surveillance.
Design and Setting
Retrospective cohort study of patients with TB in the Dominican Republic,
Hong Kong Special Administrative Region (People's Republic of China), Italy,
Ivanovo Oblast (Russian Federation), the Republic of Korea, and Peru.
New and retreatment TB cases who received short-course chemotherapy
with isoniazid, rifampicin, pyrazinamide, and either ethambutol or streptomycin
between 1994 and 1996.
Main Outcome Measure
Treatment response according to WHO treatment outcome categories (cured;
died; completed, defaulted, or failed treatment; or transferred).
Of the 6402 culture-positive TB cases evaluated, 5526 (86%) were new
cases and 876 (14%) were retreatment cases. A total of 1148 (20.8%) new cases
and 390 (44.5%) retreatment cases were drug resistant, including 184 and 169
cases of multidrug-resistant TB, respectively. Of the new cases 4585 (83%)
were treated successfully, 138 (2%) died, and 151 (3%) experienced short-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-resistant TB cases than among new susceptible
cases. Even in settings using 100% direct observation, cases with multidrug
resistance had a significantly higher failure rate than those who were susceptible
(9/94 [10%] vs 8/1410 [0.7%]; RR, 16.9; 95% CI, 6.6-42.7; P<.001). Treatment failure was also higher among patients with any
rifampicin resistance (n=115) other than multidrug resistance (RR, 5.48; 95%
CI, 3.04-9.87; P<.001), any isoniazid resistance
(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 in those with multidrug-resistant TB, with any
isoniazid resistance other than multidrug resistance, and in cases with TB
resistant to isoniazid only.
These data suggest that standard short-course chemotherapy, based on
first-line drugs, is an inadequate treatment for some patients with drug-resistant
TB. Although the directly observed treatment short-course strategy is the
basis of good TB control, the strategy should be modified in some settings
to identify drug-resistant cases sooner, and to make use of second-line drugs
in appropriate treatment regimens.