Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis

Antimicrob Agents Chemother. 2020 Apr 21;64(5):e01956-19. doi: 10.1128/AAC.01956-19. Print 2020 Apr 21.

Abstract

This study was conducted in treatment-naive adults with drug-susceptible pulmonary tuberculosis in Port-au-Prince, Haiti, to assess the safety, bactericidal activity, and pharmacokinetics of nitazoxanide (NTZ). This was a prospective phase II clinical trial in 30 adults with pulmonary tuberculosis. Twenty participants received 1 g of NTZ orally twice daily for 14 days. A control group of 10 participants received standard therapy over 14 days. The primary outcome was the change in time to culture positivity (TTP) in an automated liquid culture system. The most common adverse events seen in the NTZ group were gastrointestinal complaints and headache. The mean change in TTP in sputum over 14 days in the NTZ group was 3.2 h ± 22.6 h and was not statistically significant (P = 0.56). The mean change in TTP in the standard therapy group was significantly increased, at 134 h ± 45.2 h (P < 0.0001). The mean NTZ MIC for Mycobacterium tuberculosis isolates was 12.3 μg/ml; the mean NTZ maximum concentration (Cmax) in plasma was 10.2 μg/ml. Negligible NTZ levels were measured in sputum. At the doses used, NTZ did not show bactericidal activity against M. tuberculosis Plasma concentrations of NTZ were below the MIC, and its negligible accumulation in pulmonary sites may explain the lack of bactericidal activity. (This study has been registered at ClinicalTrials.gov under identifier NCT02684240.).

Keywords: bactericidal activity; nitazoxanide; tuberculosis.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antitubercular Agents / adverse effects
  • Antitubercular Agents / pharmacokinetics*
  • Antitubercular Agents / therapeutic use*
  • Female
  • Haiti
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Nitro Compounds / adverse effects
  • Nitro Compounds / pharmacokinetics*
  • Nitro Compounds / therapeutic use*
  • Sputum / microbiology
  • Thiazoles / adverse effects
  • Thiazoles / pharmacokinetics*
  • Thiazoles / therapeutic use*
  • Tuberculosis, Pulmonary / drug therapy*
  • Young Adult

Substances

  • Antitubercular Agents
  • Nitro Compounds
  • Thiazoles
  • nitazoxanide

Associated data

  • ClinicalTrials.gov/NCT02684240