Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis.
BACKGROUND
Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis (TB) chemotherapy, but data regarding its activity in humans are limited.


OBJECTIVE
Our objective was to compare the antimicrobial activity and safety of moxifloxacin versus isoniazid during the first 8 weeks of combination therapy for pulmonary TB.


METHODS
Adults with sputum smear-positive pulmonary TB were randomly assigned to receive either moxifloxacin 400 mg plus isoniazid placebo, or isoniazid 300 mg plus moxifloxacin placebo, administered 5 days/week for 8 weeks, in addition to rifampin, pyrazinamide, and ethambutol. All doses were directly observed. Sputum was collected for culture every 2 weeks. The primary outcome was negative sputum culture at completion of 8 weeks of treatment.


RESULTS
Of 433 participants enrolled, 328 were eligible for the primary efficacy analysis. Of these, 35 (11%) were HIV positive, 248 (76%) had cavitation on baseline chest radiograph, and 213 (65%) were enrolled at African sites. Negative cultures at Week 8 were observed in 90/164 (54.9%) participants in the isoniazid arm, and 99/164 (60.4%) in the moxifloxacin arm (P = 0.37). In multivariate analysis, cavitation and enrollment at an African site were associated with lower likelihood of Week-8 culture negativity. The proportion of participants who discontinued assigned treatment was 31/214 (14.5%) for the moxifloxacin group versus 22/205 (10.7%) for the isoniazid group (RR, 1.35; 95% CI, 0.81, 2.25).


CONCLUSIONS
Substitution of moxifloxacin for isoniazid resulted in a small but statistically nonsignificant increase in Week-8 culture negativity.
Dorman
Susan E
SE
Johns Hopkins University Center for Tuberculosis Research, Baltimore, Maryland 21231, USA. dsusan1@jhmi.edu
Johnson
John L
JL
Goldberg
Stefan
S
Muzanye
Grace
G
Padayatchi
Nesri
N
Bozeman
Lorna
L
Heilig
Charles M
CM
Bernardo
John
J
Choudhri
Shurjeel
S
Grosset
Jacques H
JH
Guy
Elizabeth
E
Guyadeen
Priya
P
Leus
Maria Corazon
MC
Maltas
Gina
G
Menzies
Dick
D
Nuermberger
Eric L
EL
Villarino
Margarita
M
Vernon
Andrew
A
Chaisson
Richard E
RE
D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001372:Aza Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D024841:Fluoroquinolones; D005500:Follow-Up Studies; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D000077266:Moxifloxacin; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
D000995:Antitubercular Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin; D007538:Isoniazid