Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis

Am J Respir Crit Care Med. 2009 Aug 1;180(3):273-80. doi: 10.1164/rccm.200901-0078OC. Epub 2009 Apr 30.

Abstract

Rationale: 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.

Objectives: 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.

Measurements and main 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.

Trial registration: ClinicalTrials.gov NCT00144417.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / therapeutic use*
  • Aza Compounds / administration & dosage
  • Aza Compounds / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Fluoroquinolones
  • Follow-Up Studies
  • Humans
  • Isoniazid / administration & dosage
  • Isoniazid / therapeutic use*
  • Male
  • Moxifloxacin
  • Mycobacterium tuberculosis / isolation & purification
  • Quinolines / administration & dosage
  • Quinolines / therapeutic use*
  • Retrospective Studies
  • Sputum / microbiology
  • Treatment Outcome
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / microbiology

Substances

  • Antitubercular Agents
  • Aza Compounds
  • Fluoroquinolones
  • Quinolines
  • Moxifloxacin
  • Isoniazid

Associated data

  • ClinicalTrials.gov/NCT00144417