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

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Antimicrobial Agents and Chemotherapy, November 1998, p. 2836-2840, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Francis Mégraud,¹^,^* Alessandra Occhialini,¹ and Jean François Rossignol²

Laboratoire de Bactériologie, Hôpital Pellegrin, 33076 Bordeaux Cedex, France,¹ and The Romark Institute for Medical Research, Tampa, Florida²

Received 18 March 1998/Returned for modification 17 June 1998/Accepted 20 August 1998

Nitazoxanide, a thiazolide compound, and its desacetyl derivative, tizoxanide, have antimicrobial properties against anaerobicbacteria, as well as against helminths and protozoa. Because thetreatment of Helicobacter pylori infection may be jeopardizedby metronidazole resistance, nitazoxanide and tizoxanide weretested in vitro against these bacteria. The MICs of these twocompounds were determined by agar dilution and were compared tothose of metronidazole. Exposure to subinhibitory concentrationsof 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 rangedfrom 0.25 to 8 µg/ml, with the MIC at which 50% of strains areinhibited (MIC₅₀) being 1 µg/ml and the MIC₉₀ being 4 µg/ml, andno resistant strain was detected, whereas strains resistant tometronidazole were detected. When 10 strains were successivelysubcultured on medium containing nitazoxanide, no significantchange in the MICs of this compound was observed. A pilot studyof nitazoxanide for the treatment of H. pylori infection was carriedout 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 receiving1 g of nitazoxanide orally twice daily, and a few side effectswere observed. The failures could not be explained by the selectionof resistant strains since the MICs of nitazoxanide were similarfor six pairs of isolates (proven to be the same strain by randomamplified polymorphic DNA analysis in four cases) cultured beforeand after the treatment failure. Nitazoxanide exhibits good antimicrobialactivity against H. pylori without the problem of acquired resistancewhich is encountered with metronidazole and has been demonstratedto have a satisfactory effect in a dose-ranging pilot study. Itis therefore a good candidate to be included in treatment regimensaimed at the eradication of H. pylori.

^* Corresponding author. Mailing address: Laboratoire de Bactériologie, Hôpital Pellegrin, 33076 Bordeaux Cedex, France. Phone:33 5 56 79 59 10. Fax: 33 5 56 79 60 18. E-mail: francis.megraud{at}chu-aquitaine.fr.

Antimicrobial Agents and Chemotherapy, November 1998, p. 2836-2840, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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