Hospital specificity, region specificity, and fluconazole resistance of Candida albicans bloodstream isolates

Abstract

In a survey of bloodstream infection (BSI) isolates across the continental United States, 162 Candida albicans isolates were fingerprinted with the species-specific probe Ca3 and the patterns were analyzed for relatedness with a computer-assisted system. The results demonstrate that particular BSI strains are more highly concentrated in particular geographic locales and that established BSI strains are endemic in some, but not all, hospitals in the study and undergo microevolution in hospital settings. The results, however, indicate no close genetic relationship among fluconazole-resistant BSI isolates in the collection, either from the same geographic locale or the same hospital. This study represents the first of three fingerprinting studies designed to analyze the origin, genetic relatedness, and drug resistance of Candida isolates responsible for BSI.

FIG. 1

Geographical separations and the locations of hospitals from which one or more BSI isolates of C. albicans were obtained. Dashed lines delineate the following geographical locales: NE, SE, MW, SW, and NW. The solid line separates East and West sections of the continental United States.

FIG. 2

Examples of the Ca3 Southern blot hybridization patterns of the C. albicans BSI isolates tested in this study. (A) Example of one of the test blots in this study. Note that the standard strain 3153A is run in the first and last lanes to normalize the gel for comparison to the universal standard in the Dendron program. (B) Patterns of isolates from New York hospital NYB. At the bottom of each gel, comparison of the patterns at S_AB thresholds of ≥0.90 and ≥0.80 are made. The checkmarks indicate the relatedness of the patterns at these thresholds. Molecular sizes (in kilobases) are given to the left of each gel.

FIG. 3

Distributions, average S_ABs, and number of pairwise comparisons (N) of all isolates (A), NE isolates (B), SE isolates (C), MW isolates (D), NW isolates (E), and SW isolates (F). S_ABs are presented as average ± standard deviation. The solid vertical line notes the average S_AB computed for unrelated isolates (20). Dashed vertical lines note the average S_AB of each respective collection.

FIG. 4

Distributions, average S_ABs, and number of comparisons (N) of complete East collection (A), East collection minus MW collection (B), East collection minus SE collection (C), and complete West collection (D). See legend to Fig. 3 for details.

FIG. 5

Dendrograms of the C. albicans collections from the NE (A), SE (B), MW (C), SW (D), and NW (E). The vertical line within each diagram denotes the S_AB threshold of 0.80. The lines to the right of each dendrogram delineate clusters based on an S_AB threshold of ≥0.80.

FIG. 6

Dendrograms of collections from individual hospitals. Vertical solid and dashed lines denote S_AB thresholds of 0.80 and 0.90, respectively. The average ± standard deviation S_AB for each collection is noted at the top of each panel.