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A prospective analysis of the genotypic diversity and dynamics of the Candida albicans colonizing flora in neutropenic patients with de novo acute leukemia

¹ Laboratoire de Parasitologie Mycologie, CHU, Hôpital du Bocage, Dijon Cedex;
² Laboratoire Interaction Muqueuses-Agents Transmissibles, IFR Santé-STIC, Université de Bourgogne, Faculté de Médecine, Dijon Cedex;
³ Service d’Hématologie Clinique, Hôpital d’Enfants, Dijon Cedex;
⁴ Institut de Mathématiques de Bourgogne, UFR Sciences et Techniques, Dijon, France

Correspondence: Frédéric Dalle, Laboratoire de Parasitologie Mycologie, Hôpital du Bocage, BP 77 908, 21079 Dijon Cedex, France. E-mail: frederic.dalle{at}chu-dijon.fr

ABSTRACT

Background: Genotyping studies have shown heterogeneity of Candida albicans flora in patients with human immunodeficiency virus infection, with possible co-existence of multiple clones with distinct resistance patterns. We report the result of a prospective study aimed at investigating the dynamics and heterogeneity of C. albicans flora in patients with de novo acute leukemia.

Design and Methods: Between 2001 and 2003, 66 consecutive adults with newly diagnosed acute leukemia were monitored for Candida colonization. From 19 patients with repeated multi-site C. albicans colonization, eight were randomly selected and multiple isolates from each individual mucosal site were genotyped sequentially over time using microsatellite markers.

Results: Despite topical use of polyenes, 60.6% of the patients were colonized repeatedly and at multiple sites. Altogether, 2,730 peripheral samples were cultured, 379 (13.9%) of which yielded yeasts. C. albicans was the most common species recovered (68%). From eight randomly selected patients colonized with C. albicans, 429 isolates were genotyped. Seven patients carried a unique genotype which was identical in all body niches and over the period of study. In one case, minor genotypic differences were observed. None of the patients shared C. albicans clones with identical genotypic profiles. Candidemia occurred in one of eight patients and the blood strain genotype did not differ from those of colonizing isolates. The genotypic profile was not altered by topical and/or systemic use of antifungal agents in any of the patients.

Conclusions: In patients with de novo acute leukemia, genetic evolution of the colonizing C. albicans flora and selection of variants or replacement of the original strain upon antifungal drug pressure or nosocomial transmission are rare events.

Key words: Candida albicans, de novo leukemia, microsatellite, diversity, antifungal resistance.