Nitazoxanide, a Potential Drug for Eradication of Helicobacter pylori with No Cross-Resistance to Metronidazole

Abstract

ABSTRACT 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 μg/ml, with the MIC at which 50% of strains are inhibited (MIC 50 ) being 1 μg/ml and the MIC 90 being 4 μg/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 .