Biofilm production has been implicated as a potential virulence factor of some Candida species responsible for catheter-related fungemia in patients receiving parenteral nutrition. We therefore compared clinical bloodstream isolates representing seven different Candida species to each other and to those from other anatomical sites for the capacity to form biofilms in glucose-containing medium. Potential associations between the capacity to form biofilms and the clinical characteristics of fungemia were also analyzed. Isolates included the following from nonneutropenic patients: 101 bloodstream isolates (35 C. parapsilosis, 30 C. albicans, 18 C. tropicalis, 8 C. glabrata, and 10 other Candida species isolates) and 259 clinical isolates from other body sites (116 C. albicans, 53 C. glabrata, 43 C. tropicalis, 17 C. parapsilosis, and 30 other Candida species isolates). Organisms were grown in Sabouraud dextrose broth (SDB) containing a final concentration of 8% glucose to induce biofilm formation, as published previously. Biofilm production was determined by both visual and spectrophotometric methods. In this medium, biofilm production by C. albicans isolates was significantly less frequent (8%) than that by non-C. albicans Candida species (61%; P < 0.0001). The overall proportion of non-C. albicans Candida species isolates from the blood that produced biofilms was significantly higher than that of non-C. albicans Candida isolates obtained from other sites (79% versus 52%; P ‫؍‬ 0.0001). Bloodstream isolates of C. parapsilosis alone were significantly more likely to be biofilm positive than were C. parapsilosis isolates from other sites (86% versus 47%; P ‫؍‬ 0.0032). Non-C. albicans Candida species, including C. parapsilosis, were more likely to be biofilm positive if isolates were derived from patients whose candidemia was central venous catheter (CVC) related (95%; P < 0.0001) and was associated with the use of total parenteral nutrition (TPN) (94%; P < 0.005). These data suggest that the capacity of Candida species isolates to produce biofilms in vitro in glucose-containing SDB may be a reflection of the pathogenic potential of these isolates to cause CVC-related fungemia in patients receiving TPN.

Background. Candida haemulonii, a yeast species that often exhibits antifungal resistance, rarely causes human infection. During 2004-2006, unusual yeast isolates with phenotypic similarity to C. haemulonii were recovered from 23 patients (8 patients with fungemia and 15 patients with chronic otitis media) in 5 hospitals in Korea. Methods. Isolates were characterized using D1/D2 domain and ITS gene sequencing, and the susceptibility of the isolates to 6 antifungal agents was tested in vitro. Results. Gene sequencing of the blood isolates confirmed C. haemulonii group I (in 1 patient) and Candida pseudohaemulonii (in 7 patients), whereas all isolates recovered from the ear were a novel species of which C. haemulonii is its closest relative. The minimum inhibitory concentration (MIC) ranges of amphotericin B, fluconazole, itraconazole, and voriconazole for all isolates were 0.5-32 microg/mL (MIC(50), 1 microg/mL), 2-128 microg/mL (MIC(50), 4 microg/mL), 0.125-4 microg/mL (MIC(50), 0.25 microg/mL), and 0.03-2 microg/mL (MIC(50), 0.06 microg/mL), respectively. All isolates were susceptible to caspofungin (MIC, 0.125-0.25 microg/mL) and micafungin (MIC, 0.03-0.06 microg/mL). All cases of fungemia occurred in patients with severe underlying diseases who had central venous catheters. Three patients developed breakthrough fungemia while receiving antifungal therapy, and amphotericin B therapeutic failure, which was associated with a high MIC of amphotericin B (32 microg/mL), was observed in 2 patients. Conclusions. Candida species that are closely related to C. haemulonii are emerging sources of infection in Korea. These species show variable patterns of susceptibility to amphotericin B and azole antifungal agents.

Emergence of Candida haemulonii and closely related species at five Korean hospitals has been recently described. We examined biofilm formation by these isolates and assessed their genotypic relatedness by pulsed-field gel electrophoresis (PFGE). This study is the first to show that all bloodstream isolates of Candida pseudohaemulonii can form significant biofilms in glucose-containing medium. PFGE of NotI-digested genomic DNA revealed that C. pseudohaemulonii isolates recovered from seven patients in two hospitals shared five patterns, and that 15 isolates of a proposed new species (Candida auris) obtained from patients at three hospitals shared seven patterns, suggesting that some of these isolates may be related to clonal transmission.

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