Early bactericidal activity trial of nitazoxanide for pulmonary tuberculosis.

SettingThis study was conducted in treatment-naïve adults with drug-susceptible pulmonary tuberculosis in Port-au-Prince, Haiti.ObjectiveTo assess the safety, bactericidal activity and pharmacokinetics of nitazoxanide (NTZ).DesignThis was a prospective phase II clinical trial in 30 adults with pulmonary tuberculosis. Twenty participants received NTZ 1 gram orally twice daily for 14 days. A control group of ten participants received standard therapy over 14 days. The primary outcome was the change in time to culture positivity in an automated liquid culture system.ResultsThe 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 hours ± 22.6 and was not statistically significant (p=0.56). The mean change in TTP in the standard therapy group was significantly increased, at 134 hours ± 45.2 (p<0.0001). The mean NTZ minimum inhibitory concentration for M. tuberculosis isolates was 12.3 μg/mL; the mean NTZ plasma C_max was 10.2 μg/mL. Negligible NTZ levels were measured in sputum.ConclusionAt 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.