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

Am J Respir Crit Care Med. 2006 Nov 15;174(10):1153-8. doi: 10.1164/rccm.200605-637OC. Epub 2006 Aug 14.


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.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antitubercular Agents / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Humans
  • Logistic Models
  • ROC Curve
  • Recurrence
  • Rifamycins / administration & dosage*
  • Sputum / microbiology
  • Tuberculosis, Pulmonary / prevention & control*


  • Antitubercular Agents
  • Rifamycins