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Dosing Schedules of 6-Month Regimens and Relapse for Pulmonary Tuberculosis

Tuberculosis and Chest Service, Center for Health Protection, Department of Health; Tuberculosis and Chest Unit, Grantham Hospital; and Hong Kong Tuberculosis, Chest, and Heart Diseases Association, Hong Kong, China

Correspondence and requests for reprints should be addressed to Dr. Kwok Chiu Chang, M.B., M.Sc., Yaumatei Chest Clinic, 2nd Floor, Yaumatei Jockey Club Polyclinic, 145 Battery Street, Kowloon, Hong Kong. E-mail: kc_chang{at}dh.gov.hk

Rationale: The optimal approach for reducing tuberculosis relapse is open.

Objectives: We examined the possibility of reducing relapse by increasing dosing schedules.

Methods: We conducted a systematic review of published clinical trials involving adult cohorts with pulmonary tuberculosis treated using 6-mo rifamycin-containing regimens, which were grouped under seven categories ordered by dosing schedules. Assuming cavitation and positive 2-mo culture were the driving forces for relapse, a static deterministic model apportioned observed numbers with and without relapse in each cohort into eight subgroups. Combining subgroups stratified by cavitation, 2-mo culture, and regimens enabled estimation of adjusted relapse risks. ² Tests for trend and logistic regression analysis examined the relationship between relapse and dosing schedules.

Results: We identified 200 cases of bacteriologic relapse out of 5,208 patients in 32 cohorts. A logistic risk model showed a significant dose–response relationship between dosing schedules and relapse, with the following odds (95% confidence intervals) of relapse relative to daily regimens: 1.6 (0.6–4.1) for daily initial phase (IP) plus thrice-weekly continuation phase (CP), 2.8 (1.3–6.1) for daily IP plus twice-weekly CP, 2.8 (1.4–5.7) for thrice-weekly, 5.0 (2.4–10.5) for daily IP plus once-weekly rifapentine, and 7.1 (3.3–15.3) for thrice-weekly IP plus once-weekly rifapentine. In the presence of cavitation, only 6-mo daily or daily IP plus thrice-weekly CP attained best-estimated relapse risks below 5%; they reached 6% when 2-mo culture was also positive.

Conclusions: Cavitary tuberculosis is best treated with 6-mo regimens comprising daily IP and thrice-weekly CP, which may be extended when 2-mo culture is positive.

Key Words: logistic models • relapse • risk factors • treatment • tuberculosis

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Although extending treatment of 6-month regimens may reduce relapse of tuberculosis, the optimal approach for reducing relapse has not been determined. What This Study Adds to the Field A dose–response relationship exists between relapse and dosing schedules of 6-month regimens. Increasing dosing schedules may reduce relapse.

 

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