title: Dosing schedules of 6-month regimens and relapse for pulmonary tuberculosis.
abstract: BACKGROUND
  The optimal approach for reducing tuberculosis relapse is open.
  
  
  OBJECTIVE
  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.
authors.affiliation: Tuberculosis and Chest Service, Center for Health Protection, Department of Health; Tuberculosis and Chest Unit, Grantham Hospital, Hong Kong, China. kc_chang@dh.gov.hk
authors.forename: Kwok C
authors.initials: KC
authors.lastname: Chang
authors.forename: Chi C
authors.initials: CC
authors.lastname: Leung
authors.forename: Wing W
authors.initials: WW
authors.lastname: Yew
authors.forename: Shiu L
authors.initials: SL
authors.lastname: Chan
authors.forename: Cheuk M
authors.initials: CM
authors.lastname: Tam
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D016015:Logistic Models; D012372:ROC Curve; D012008:Recurrence; D012294:Rifamycins / Q000008:administration & dosage*; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control*
chemical_list: D000995:Antitubercular Agents; D012294:Rifamycins