CHANGE IN FLUCONAZOLE SUSCEPTIBILITY PATTERNS AND GENETIC-RELATIONSHIP AMONG ORAL CANDIDA-ALBICANS ISOLATES

Objective: To assess the genetic homogeneity or heterogeneity within e ach set of Candida albicans isolates colonizing/infecting the oral cav ities of HIV-infected patients undergoing azole therapy when changes i n susceptibility to fluconazole were detected. Design: Fourteen HIV-po sitive patients suffering recurrent episodes of oral candidosis were p rospectively followed from the first episode to the isolation of strai ns with decreased susceptibility to fluconazole. The strains of C. alb icans isolated either from episodes or controls throughout the prospec tive study were analysed. Methods: Electrophoretic karyotyping and hyb ridization with the repeated sequence probe 27A were used to delineate sequential isolates. In vitro susceptibility tests to fluconazole and ketoconazole were also performed. The results obtained by DNA fingerp rinting with the probe combined with computer-assisted analysis were u sed to assess the genetic relationships amongst the strains. In additi on, comparison with the genetic relatedness of a group of geographical ly unrelated strains was made. Results: Isogenic populations of sequen tial isolates were observed only in two patients; 12 patients harboure d heterogenic populations over time, although in 11 patients there was a predominant strain that was isolated more than once, and only one o f these patients carried strains with a similarity index less than 80% . With the exception of two patients, each patient carried a major str ain that became less susceptible to fluconazole. The similarity index for the unrelated strains was 59%. Conclusions: HIV-infected patients may carry a mixed population of strains, but the strains tend to be re lated to each other. The strains were maintained throughout the course of infection and at least one developed secondary resistance to Fluco nazole. (C) 1998 Lippincott Williams & Wilkins.