NITAZOXANIDE, A POTENTIAL-DRUG FOR ERADICATION OF HELICOBACTER-PYLORIWITH NO CROSS-RESISTANCE TO METRONIDAZOLE

Nitazoxanide, a thiazolide compound, and its desacetyl derivative, tiz oxanide, have antimicrobial properties against anaerobic bacteria, as well as against helminths and protozoa. Because the treatment of Helic obacter pylori infection may be jeopardized by metronidazole resistanc e, nitazoxanide and tizoxanide were tested in vitro against these bact eria. The MICs of these two compounds were determined by agar dilution and were compared to those of metronidazole, Exposure to subinhibitor y 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 mu g/ml, with the MIC at which 50% of strains are inhibited (MIC50) being 1 mu g/ml and the MIC90 being 4 mu g/ml, and no resista nt strain was detected, whereas strains resistant to metronidazole wer e detected. When 10 strains were successively subcultured on medium co ntaining nitazoxanide, no significant change in the MICs of this compo und was observed. A pilot study of nitazoxanide for the treatment of H . pylori infection was carried out with 86 patients in association wit h 20 mg of omeprazole, An eradication rate of 83% (95% confidence inte rval, 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 effe cts were observed. The failures could not be explained by the selectio n of resistant strains since the MICs of nitazoxanide were similar for six pairs of isolates (proven to be the same strain by random amplifi ed polymorphic DNA analysis in four cases) cultured before and after t he treatment failure. Nitazoxanide exhibits good antimicrobial activit y against H. pylori without the problem of acquired resistance which i s encountered with metronidazole and has been demonstrated to have a s atisfactory effect in a dose-ranging pilot study. It is therefore a go od candidate to be included in treatment regimens aimed at the eradica tion of H. pylori.