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Antimicrobial Agents and Chemotherapy, January 1999, p. 73-76, Vol. 43, No. 1
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Efficacy of New 5-Nitroimidazoles against Metronidazole-Susceptible and -Resistant Giardia, Trichomonas, and Entamoeba spp.

Jacqueline A. Upcroft,1,* Raymond W. Campbell,1 Kamel Benakli,2 Peter Upcroft,1 and Patrice Vanelle2

The Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia,1 and Laboratoire de Chimie Organique, Université de la Méditerranée, Faculté de Pharmacie, 13385 Marseille Cedex 05, France2

Received 17 February 1998/Returned for modification 19 June 1998/Accepted 12 October 1998

The efficacies of 12 5-nitroimidazole compounds and 1 previously described lactam-substituted nitroimidazole with antiparasitic activity, synthesized via SRN1 and subsequent reactions, were assayed against the protozoan parasites Giardia duodenalis, Trichomonas vaginalis, and Entamoeba histolytica. Two metronidazole-sensitive lines and two metronidazole-resistant lines of Giardia and one line each of metronidazole-sensitive and -resistant Trichomonas were tested. All except one of the compounds were as effective or more effective than metronidazole against Giardia and Trichomonas, but none was as effective overall as the previously described 2-lactam-substituted 5-nitroimidazole. None of the compounds was markedly more effective than metronidazole against Entamoeba. Significant cross-resistance between most of the drugs tested and metronidazole was evident among metronidazole-resistant lines of Giardia and Trichomonas. However, some drugs were lethal to metronidazole-resistant Giardia and had minimum lethal concentrations similar to that of metronidazole for drug-susceptible parasites. This study emphasizes the potential in developing new nitroimidazole drugs which are more effective than metronidazole and which may prove to be useful clinical alternatives to metronidazole.

* Corresponding author. Mailing address: The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia. Phone: 61 7 3362 0369. Fax: 61 7 3362 0105. E-mail: jacquiU{at}qimr.edu.au.

Antimicrobial Agents and Chemotherapy, January 1999, p. 73-76, Vol. 43, No. 1
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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