Candida dubliniensis

Candida dubliniensis is an organism often associated with AIDS patients but can be associated with immunocompetent patients as well. It is a germ cell-positive yeast of the genus Candida, similar to Candida albicans but it forms a different cluster upon DNA fingerprinting. It appears to be particularly adapted for the mouth^[1] but can be found at very low rates in other anatomical sites.

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Prevalence and epidemiology

Candida dubliniensis is found all around the world. The species was only described in 1995.^[2] It is thought to have been previously identified as Candida albicans. Retrospective studies support this, and have given an indication of the prevalence of C. dubliniensis as a laboratory pathogen.

The most useful test for distinguishing C. dubliniensis from C. albicans, is to culture at 42°C. Most C. albicans grows well at this temperature,^[3] but most C. dubliniensis does not.^[2] There are also significant differences in the chlamydiospores between C. albicans and C. dubliniensis although they are otherwise phenotypically very similar.^[2]

A study done in Europe of 2,589 isolates, that were originally reported as C. albicans, revealed that 52 of them (2.0%) were actually C. dubliniensis. Most of these isolates were from oral or faecal specimens from HIV positive patients, though one vaginal and two oral isolates were from healthy volunteers. Another study done in the United States, used 1,251 yeasts previously identified as C. albicans, it found 15 (1.2%) were really C. dubliniensis. Most of these samples were from immunocompromised individuals: AIDS, chemotherapy, or organ transplant patients. The yeast was most often recovered from repiratory, urine and stool specimens. The Memorial Sloan-Kettering Cancer Center also did several studies, both retrospective, and current. In all 974 germ-tube positive yeasts, 22 isolates (2.3%) from 16 patients were C. dubliniesis. Fifteen of these patients were adults, one a child. Nine were male, 7 were female. All were immunologically compromised with either malignancy or AIDS. The isolates came from a variety of different sites.

Candida dubliniensis is an opportunistic pathogen that can cause both superficial and invasive infections, (mostly in the immunocompromised). About 1-2% of isolates once identified as C. albicans, were subsequently found to be C. dubliniensis. This is most likely still the case now, 1-2% of GCT positive yeasts are probably C. dubliniensis. Interestingly, this species was isolated in the mouths of 18% of patients with diabetes who use insulin.^[4] It is clear that this species can been seen in healthy patients as well as immunocompromised patients.

Antifungal susceptibility

Most of the isolates of C. dubliniensis are from people who are immunocompromised. Antimicrobial susceptibility is important, as these patients often receive long-term treatment with various anti-fungal drugs. In one small study, all 20 isolates were susceptible to itraconazole, ketoconazole and amphotericin B.^[5]

Fluconazole

Most isolates of C. dubliniensis appear to be sensitive to fluconazole. In one study, 16 of 20 isolates were sensitive to fluconazole, while four were resistant.^[5] It has been hypothesized that C. dubliniensis has the ability to rapidly develop resistance to fluconazole, especially in patients who are on long-term therapy.^[5]

Stable fluconazole resistance could be induced (in vitro) by subjecting sensitive strains to increasing concentrations of the antifungal. This resistance is mediated by a multidrug transporter that can be mobilized rapidly in vitro, on exposure to fluconazole. An AIDS patient in Germany, who had been treated with fluconazole for 18 months, became unresponsive to fluconazole 400 mg/day.

Cases in America have also shown the emergence of fluconazole resistant C. dubliniensis. Three isolates were discovered in Texas, two were resistant (MIC, 64 µg/mL). And one had dose-dependent susceptibility (MIC, 16 µg/mL). In a test on C. dubliniensis in HIV+ patients in Maryland, most isolates were highly susceptible to fluconazole, though one was dose-dependent susceptible, (16 µg/mL), meaning a high dose of fluconazole given to the patient would halt the yeast. A study of 71 isolates in Ireland, showed that both the fluconazole resistant and susceptible strains were susceptible to itraconazole, amphotericin B, and 5-fluorocytosine (microdilution). They were also susceptible to investigational triazoles and voriconazole, also echinocandin.

It seems C. dubliniensis is very prone to being resistant to fluconazole, or at least need a higher dose. It still retains susceptibility to the other common antifungals, and some investigational new antimicrobials, which can be used when fluconazole fails.

References

1. ^ Gilfillan GD, Sullivan DJ, Haynes K, Parkinson T, Coleman DC, Gow NAR (1998). "Candida dubliniensis: Phylogeny and putative virulence factors". Microbiology 144 (4): 829-838.
2. ^ ^{a b c} Sullivan DJ, Westerneng TJ, Haynes KA, Bennett DE, Coleman DC (1995). "Candida dubliniensis sp. nov.: phenotypic and molecular characterization of a novel species associated with oral candidosis in HIV-infected individuals". Microbiol. 141: 1507–1521.
3. ^ Kamiyama A, Niimi M, Tokunaga M,. Nakayama H (1989). "Adansonian study of Candida albicans: intraspecific homogeneity excepting C. stellatoideastrains". J Med Vet Mycol 27: 229–241.
4. ^ Willis AM, Coulter WA, Sullivan DJ, Coleman DC, Hayes JR, Bell PM, Lamey PJ (2000). "Isolation of C. dubliniensis from insulin-using diabetes mellitus patients". J Oral Path & Med. 29 (2): 86–90. doi:10.1034/j.1600-0714.2000.290206.x.
5. ^ ^{a b c} Moran GP, Sullivan DJ, Henman MC, McCreary CE, Harrington BJ, Shanley DB, Coleman DC (1997 Mar). "Antifungal drug susceptibilities of oral Candida dubliniensis isolates from human immunodeficiency virus (HIV)-infected and non-HIV-infected subjects and generation of stable fluconazole-resistant derivatives in vitro". Antimicrob. Agents Chemother. 41 (3): 617.

External links

• Doctor Fungus page about Candida dubliniensis