Nitazoxanide, a thiazolide compound, and its desacetyl derivative,
tizoxanide, have antimicrobial properties against anaerobic bacteria, as well as against helminths and protozoa. Because the treatment of Helicobacter pylori
infection may be jeopardized by
metronidazole resistance,
nitazoxanide and
tizoxanide were tested in vitro against these bacteria. The MICs of these two compounds were determined by
agar dilution and were compared to those of
metronidazole. Exposure to subinhibitory concentrations of
nitazoxanide was also carried out by the method of Szybalski (W. Szybalski and V. Bryson, J. Bacteriol. 64:489-499, 1952). The MICs of
nitazoxanide and
tizoxanide for 103 strains ranged from 0.25 to 8 microg/ml, with the MIC at which 50% of strains are inhibited (MIC50) being 1 microg/ml and the MIC90 being 4 microg/ml, and no resistant strain was detected, whereas strains resistant to
metronidazole were detected. When 10 strains were successively subcultured on medium containing
nitazoxanide, no significant change in the MICs of this compound was observed. A pilot study of
nitazoxanide for the treatment of H. pylori
infection was carried out with 86 patients in association with 20 mg of
omeprazole. An eradication rate of 83% (95% confidence interval, 64% to 94%) was obtained in a per-protocol analysis in the group receiving 1 g of
nitazoxanide orally twice daily, and a few side effects were observed. The failures could not be explained by the selection of resistant strains since the MICs of
nitazoxanide were similar for six pairs of isolates (proven to be the same strain by random amplified polymorphic
DNA analysis in four cases) cultured before and after the treatment failure.
Nitazoxanide exhibits good antimicrobial activity against H. pylori without the problem of acquired resistance which is encountered with
metronidazole and has been demonstrated to have a satisfactory effect in a dose-ranging pilot study. It is therefore a good candidate to be included in treatment regimens aimed at the eradication of H. pylori.