Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis

Am J Respir Crit Care Med. 2006 Aug 1;174(3):331-8. doi: 10.1164/rccm.200603-360OC. Epub 2006 May 4.

Abstract

Rationale: Moxifloxacin has promising preclinical activity against Mycobacterium tuberculosis, but has not been evaluated in multidrug treatment of tuberculosis in humans.

Objective: To compare the impact of moxifloxacin versus ethambutol, both in combination with isoniazid, rifampin, and pyrazinamide, on sputum culture conversion at 2 mo as a measure of the potential sterilizing activity of alternate induction regimens.

Methods: Adults with smear-positive pulmonary tuberculosis were randomized in a factorial design to receive moxifloxacin (400 mg) versus ethambutol given 5 d/wk versus 3 d/wk (after 2 wk of daily therapy). All doses were directly observed.

Measurements: The primary endpoint was sputum culture status at 2 mo of treatment.

Results: Of 336 patients enrolled, 277 (82%) were eligible for the efficacy analysis, 186 (67%) were male, 175 (63%) were enrolled at African sites, 206 (74%) had cavitation on chest radiograph, and 60 (22%) had HIV infection. Two-month cultures were negative in 71% of patients (99 of 139) treated with moxifloxacin versus 71% (98 of 138) treated with ethambutol (p = 0.97). Patients receiving moxifloxacin, however, more often had negative cultures after 4 wk of treatment. Patients treated with moxifloxacin more often reported nausea (22 vs. 9%, p = 0.002), but similar proportions completed study treatment (88 vs. 89%). Dosing frequency had little effect on 2-mo culture status or tolerability of therapy.

Conclusions: The addition of moxifloxacin to isoniazid, rifampin, and pyrazinamide did not affect 2-mo sputum culture status but did show increased activity at earlier time points.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Africa
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / adverse effects
  • Antitubercular Agents / therapeutic use*
  • Aza Compounds / adverse effects
  • Aza Compounds / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Ethambutol / adverse effects
  • Ethambutol / therapeutic use*
  • Female
  • Fluoroquinolones
  • Humans
  • Male
  • Moxifloxacin
  • Mycobacterium tuberculosis / isolation & purification
  • Quinolines / adverse effects
  • Quinolines / therapeutic use*
  • Sputum / microbiology
  • Tuberculosis, Pulmonary / drug therapy*
  • United States

Substances

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