title: In vitro activity of nitazoxanide and related compounds against isolates of Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis.
abstract: The activities of the N-(nitrothiazolyl) salicylamide nitazoxanide and its metabolite tizoxanide were compared with metronidazole in vitro in microplates against six axenic isolates of Giardia intestinalis. Tizoxanide was eight times more active than metronidazole against metronidazole-susceptible isolates and twice as active against a resistant isolate. In 10 axenic isolates of Entamoeba histolytica, while tizoxanide was almost twice as active as metronidazole against more susceptible isolates, it was more than twice as active against less susceptible isolates. Fourteen metronidazole-susceptible isolates of Trichomonas vaginalis were 1.5 times more susceptible to tizoxanide, which was nearly five times as active against resistant isolates. Two highly metronidazole-resistant isolates retained complete susceptibility to tizoxanide, and one moderately resistant isolate showed reduced susceptibility. In all three organisms, nitazoxanide results paralleled those of tizoxanide. Analogues lacking the reducible nitro-group had similar low activities against susceptible G. intestinalis, E. histolytica and T. vaginalis, indicating that nitro-reduction and free radical production was a probable mode of action. Nitazoxanide and its metabolite tizoxanide are more active in vitro than metronidazole against G. intestinalis, E. histolytica and T. vaginalis. Although, like metronidazole, they depend on the presence of a nitro-group for activity, they retain some activity against metronidazole-resistant strains, particularly of T. vaginalis. The results suggest that resistance mechanisms for metronidazole can be bypassed by nitazoxanide and tizoxanide.
authors.affiliation: Romark Research Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
authors.forename: I Sullayman
authors.initials: IS
authors.lastname: Adagu
authors.forename: Deborah
authors.initials: D
authors.lastname: Nolder
authors.forename: David C
authors.initials: DC
authors.lastname: Warhurst
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rossignol
mesh_terms: D000563:Amebicides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000994:Antitrichomonal Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000502:physiology; D004748:Entamoeba histolytica / Q000187:drug effects* / Q000302:isolation & purification; D016829:Giardia lamblia / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D009574:Nitro Compounds; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014246:Trichomonas vaginalis / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000563:Amebicides; D000981:Antiprotozoal Agents; D000994:Antitrichomonal Agents; D009574:Nitro Compounds; D013844:Thiazoles; C041747:nitazoxanide