Shortening treatment in adults with noncavitary tuberculosis and 2-month culture conversion.
BACKGROUND
Cavitary disease and delayed culture conversion have been associated with relapse. Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients.


OBJECTIVE
To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months.


METHODS
This study was a randomized, open-label equivalence trial. HIV-uninfected adults with noncavitary tuberculosis were treated daily with isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by 2 months of isoniazid and rifampin. After 4 months, patients with drug-susceptible TB whose sputum cultures on solid media were negative after 8 weeks of treatment were randomly assigned to continue treatment for 2 more months or to stop treatment. Patients were followed for relapse for 30 months after beginning treatment.


RESULTS
Enrollment was stopped by the safety monitoring committee after 394 patients were enrolled due to apparent increased risk for relapse in the 4-month arm. A total of 370 patients were eligible for per protocol analysis. Thirteen patients in the 4-month arm relapsed, compared with three subjects in the 6-month arm (7.0 vs. 1.6%; risk difference, 0.054; 95% confidence interval with Hauck-Anderson correction, 0.01-0.10).


CONCLUSIONS
Shortening treatment from 6 to 4 months in adults with noncavitary disease and culture conversion after 2 months using current drugs resulted in a greater relapse rate. The combination of noncavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse.
Johnson
John L
JL
Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio 44106-5083, USA. jlj@case.edu
Hadad
David Jamil
DJ
Dietze
Reynaldo
R
Maciel
Ethel Leonor Noia
EL
Sewali
Barrett
B
Gitta
Phineas
P
Okwera
Alphonse
A
Mugerwa
Roy D
RD
Alcaneses
Mary Rose
MR
Quelapio
Maria Imelda
MI
Tupasi
Thelma E
TE
Horter
Libby
L
Debanne
Sara M
SM
Eisenach
Kathleen D
KD
Boom
W Henry
WH
D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008297:Male; D009169:Mycobacterium tuberculosis / Q000254:growth & development*; D016016:Proportional Hazards Models; D011718:Pyrazinamide / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology
D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin