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Am J Respir Crit Care Med. 2006 Nov 15;174(10):1153-8. Epub 2006 Aug 14.

Dosing schedules of 6-month regimens and relapse for pulmonary tuberculosis.

Author information

  • 1Tuberculosis and Chest Service, Center for Health Protection, Department of Health; Tuberculosis and Chest Unit, Grantham Hospital, Hong Kong, China. kc_chang@dh.gov.hk

Abstract

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. chi2 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.

Comment in

PMID:
16908866
[PubMed - indexed for MEDLINE]
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