Literature DB >> 15347633

Variability and variation in drug susceptibility among Giardia duodenalis isolates and clones exposed to 5-nitroimidazoles and benzimidazoles in vitro.

Raúl Argüello-García1, Maricela Cruz-Soto, Lydia Romero-Montoya, Guadalupe Ortega-Pierres.   

Abstract

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.

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Year:  2004        PMID: 15347633     DOI: 10.1093/jac/dkh388

Source DB:  PubMed          Journal:  J Antimicrob Chemother        ISSN: 0305-7453            Impact factor:   5.790


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