Journal Article

Variability and variation in drug susceptibility among <i>Giardia duodenalis</i> isolates and clones exposed to 5-nitroimidazoles and benzimidazoles <i>in vitro</i>

Raúl Argüello-García, Maricela Cruz-Soto, Lydia Romero-Montoya and Guadalupe Ortega-Pierres

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 54, issue 4, pages 711-721
Published in print October 2004 | ISSN: 0305-7453
Published online October 2004 | e-ISSN: 1460-2091 | DOI:
Variability and variation in drug susceptibility among Giardia duodenalis isolates and clones exposed to 5-nitroimidazoles and benzimidazoles in vitro

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  • Medical Oncology
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Objectives: We analysed, in a cell-by-cell study, the in vitro susceptibility of Giardia duodenalis strains, including Mexican isolates and their clones to 5-nitroimidazoles and benzimidazoles.

Methods: Fluorogenic dye staining (FDA-PI) and cell morphology (CM) assays, two fast and direct techniques, replaced the indirect ‘gold standard’ method (subculture in liquid medium) in the evaluation of 5-nitroimidazoles and benzimidazoles, respectively.

Results: Under these conditions, the activity of several 5-nitroimidazole and benzimidazole derivatives was consistent with their known efficacy, but parasite stocks exhibited a greater variability in response to 5-nitroimidazoles compared with benzimidazoles. Also, consecutive progenies from single stocks maintained in continuous subculture in drug-free media displayed changes (variations) in the proportions of drug resistant (R/T) subpopulations when exposed to sublethal concentrations of 5-nitroimidazoles and benzimidazoles. These were again more variable upon exposure to 5-nitroimidazoles than to benzimidazoles. Variations were not due to drug susceptibility shifts in parent trophozoites since analysis of cytokinetic processes showed a predominant pattern of susceptible/susceptible or resistant/resistant daughters, whereas susceptible/resistant daughters were scarce.

Conclusions: Our observations support the idea that G. duodenalis cultures exhibit variations in their response to 5-nitroimidazoles and benzimidazoles as a result of a drug-independent competition between drug-susceptible and drug-resistant subpopulations when parasites are subcultured.

Keywords: antiprotozoal drugs; clonal variation; viability assays; cell morphology assays; dye uptake assays

Journal Article.  6451 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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