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Journal of Clinical Microbiology, August 2000, p. 3139-3140, Vol. 38, No. 8
0095-1137/00/$04.00+0

LETTERS TO THE EDITOR

One-Year Prevalence of Candida dublinienis in a Dutch University Hospital


    LETTER

With reference to a recently published article by Polacheck et al. (9) reporting the isolation of Candida dubliniensis from non-human immunodeficiency virus (HIV)-infected patients in an Israeli hospital, we would like to add our data from a single center in The Netherlands. Since we described the occurrence of candidemia due to C. dubliniensis in non-HIV-infected patients (4), we prospectively studied the prevalence of C. dubliniensis during the year 1999 in our 1,000-bed tertiary-care university hospital. All germ-tube-positive yeasts isolated from various clinical specimens submitted to the diagnostic laboratory were further examined. Germ-tube-positive yeasts were suspected to be C. dubliniensis when there was no growth at 45°C, no assimilation of xylose, and no elaboration of beta -glucosidase and when microscopic morphology showed abundant chlamydospore formation on rice-cream agar (8, 10, 12). Molecular typing with RP02 (4, 5) was used to confirm the phenotypic identification as C. dubliniensis. In 1999, a total of 3,848 yeast isolates were cultured from various clinical samples of which 2,605 (67.7%) were germ-tube positive. Of the germ-tube-positive yeasts, 21 (0.8%) isolated from 11 patients were C. dubliniensis as determined by phenotypic and molecular methods. Most isolates were recovered from oropharyngeal and fecal surveillance cultures from patients at the hematological ward (18 of 21 patients; 86%); one isolate each was cultured from a bronchial secretion, a urine specimen, and a skin biopsy specimen. Of the 11 patients, 6 (55%) were HIV negative, and of 5 patients, no antibodies against HIV were tested because there was no clinical suspicion for HIV-related disease. In vitro susceptibility testing was performed on one isolate per patient using the NCCLS broth microdilution method (6). All isolates were susceptible to amphotericin B (MIC, 0.25 mg/liter), fluconazole (MIC, 0.25 mg/liter), 5-flucytosine (MIC, <0.25 mg/liter), and itraconazole (MIC, 0.012 mg/liter). Only the patient with the positive skin biopsy specimen, without concomitant positive blood cultures, was treated with fluconazole (400 mg daily) and recovered. Yeast infections are becoming a world-wide problem, with C. albicans still the most frequently isolated species of nosocomial infections (3, 7, 11, 12). In The Netherlands, 60% of all candidemic episodes were caused by C. albicans (13). C. dubliniensis, which shares many phenotypic characteristics with C. albicans, was first described only 5 years ago for HIV-positive subjects in Ireland (12). Since the methods for correct identification of C. dubliniensis were established, the species has been reported world-wide (1, 2, 9, 10). In a recent prospective study (2) in the United States, 6 of 699 yeasts (0.9%) isolated were C. dubliniensis, a prevalence which is similar to ours. In contrast with our results, these isolates were mainly recovered from the oral cavity of HIV-positive patients. In 1999, three cases of C. dubliniensis candidemia in HIV-negative subjects were reported in Europe (4), and recently, another four cases, of which one was HIV positive, were reported in the United States (1). Although C. dubliniensis was first described in HIV-positive patients, recent data suggest that it is also common in HIV-negative patients as long as attempts are made to differentiate the isolates from C. albicans. Microbiologists should be alerted to consider C. dubliniensis when an atypical germ-tube-positive yeast is isolated because the most serious infections (six of seven) described until now have occurred in HIV-negative subjects with different forms of immunosuppression.


    FOOTNOTES

* Phone: 31-24-3614356 Fax: 31-24-3540216 E-mail: j.meis{at}cwz.nl


    REFERENCES

1. Brandt, M. E., L. H. Harrison, M. Pass, A. N. Sofair, S. Huie, R.-K. Li, C. J. Morrison, D. W. Warnock, and R. A. Hajjeh. 2000. Candida dubliniensis fungemia: the first four cases in North America. Emerg. Infect. Dis. 6:46-49[Medline].
2. Jabra, R. M., A. A. Baqui, J. I. Kelley, W. A. J. Falker, W. G. Merz, and T. F. Meiller. 1999. Identification of Candida dubliniensis in a prospective study of patients in the United States. J. Clin. Microbiol. 37:321-326[Abstract/Free Full Text].
3. Karlowsky, J. A., G. G. Zhanel, K. A. Klym, D. J. Hoban, and A. M. Kabani. 1997. Candidemia in a Canadian tertiary care hospital from 1976 to 1996. Diagn. Microbiol. Infect. Dis. 29:5-9[CrossRef][Medline].
4. Meis, J. F. G. M., M. Ruhnke, B. E. de Pauw, F. C. Odds, W. Siegert, and P. E. Verweij. 1999. Candida dubliniensis candidemia in patients with chemotherapy-induced neutropenia and bone marrow transplantation. Emerg. Infect. Dis. 5:150-153[Medline].
5. Morschauer, J. M., M. Ruhnke, S. Michel, and J. Hacker. 1999. Identification of CARE-2 negative Candida albicans as Candida dubliniensis. Mycoses 42:29-32.
6. National Committee for Clinical Laboratory Standards. 1997. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard. NCCLS document M27-A. National Committee for Clinical Laboratory Standards, Wayne, Pa.
7. Pfaller, M. A., R. N. Jones, G. V. Doern, H. S. Sader, R. J. Hollis, and S. A. Messer. 1998. International surveillance of bloodstream infections due to Candida species: frequency of occurrence and antifungal susceptibilities of isolates collected in 1997 in the United States, Canada, and South America for the SENTRY Program. The SENTRY Participant Group. J. Clin. Microbiol. 36:1886-1889.
8. Pinjon, E., D. Sullivan, I. F. Salkin, D. Shanley, and D. Coleman. 1998. Simple, inexpensive, reliable method for differentiation of Candida dubliniensis from Candida albicans. J. Clin. Microbiol. 36:2093-2095[Abstract/Free Full Text].
9. Polacheck, I., J. Strahilevitz, D. Sullivan, S. Donnelly, I. F. Salkin, and D. C. Coleman. 2000. Recovery of Candida dubliniensis from non-human immunodeficiency virus-infected patients in Israel. J. Clin. Microbiol. 38:170-174[Abstract/Free Full Text].
10. Salkin, I. F., W. R. Pruitt, A. A. Padhye, D. Sullivan, D. Coleman, and D. H. Pincus. 1998. Distinctive carbohydrate assimilation profiles used to identify the first clinical isolates of Candida dubliniensis recovered in the United States. J. Clin. Microbiol. 36:1467[Free Full Text].
11. Sandven, P., L. Bevanger, A. Digranes, P. Gaustad, H. H. Haukland, and M. Steinbakk. 1998. Constant low rate of fungemia in Norway, 1991 to 1996. The Norwegian Yeast Study Group. J. Clin. Microbiol. 36:3455-3459.
12. Sullivan, D. J., T. J. Westerneng, K. A. Haynes, D. E. Bennett, and D. C. Coleman. 1995. Candida dubliniensis sp. nov.: phenotypic and molecular characterization of a novel species associated with oral candidosis in HIV-infected individuals. Microbiology 141:1507-1521[Abstract/Free Full Text].
13. Voss, A., J. A. J. W. Kluytmans, J. G. M. Koeleman, L. Spanjaard, C. M. J. E. Vandenbroucke-Grauls, H. A. Verbrugh, M. C. Vos, A. Y. L. Weersink, J. A. A. Hoogkamp-Korstanje, and J. F. G. M. Meis. 1996. Occurrence of yeast bloodstream infections between 1987 and 1995 in five Dutch university hospitals. Eur. J. Clin. Microbiol. Infect. Dis. 15:909-912[CrossRef][Medline].
Jacques F. G. M. Meis*
Department of Medical Microbiology
Canisius Wilhelmina Hospital
Nijmegen, The Netherlands
Frans M. Verduyn Lunel
Paul E. Verweij
Andreas Voss
Department of Medical Microbiology
University Medical Center Nijmegen
Nijmegen, The Netherlands


    AUTHOR'S REPLY

We welcome the comments of Dr. Meis and colleagues and their additional data on the frequency of isolation of Candida dubliniensis from HIV-negative individuals at the University Medical Center, Nijmegen, The Netherlands. We agree that although C. dubliniensis was originally thought to be mainly associated with the oral cavity of HIV-infected and AIDS patients (3, 6, 8, 13-16), several recent studies have shown that it is more prevalent in HIV-negative individuals than perhaps originally thought (2, 5, 7-9, 15, 17). Our recent paper on the recovery of C. dubliniensis from HIV-negative patients in Israel added to this body of data and also provided the first report of the recovery of C. dubliniensis from the Middle East (12). Several studies have reported that C. dubliniensis is found as a commensal organism in HIV-negative individuals and that it can also cause overt oral and nonoral infection in this group (3, 5, 8, 9, 11, 15, 17). Our laboratory reported the first authenticated blood culture isolate of C. dubliniensis in 1998 from an HIV-negative patient (11). Since then, seven other cases of C. dubliniensis fungemia (six in HIV-negative individuals) have been reported from Europe (7) and North America (2) in patients with severe underlying medical conditions.

Because C. dubliniensis and its close relative Candida albicans share many phenotypic characteristics in common, many isolates of C. dubliniensis have been misidentified as C. albicans (3, 8-10, 13-16). This situation has been remedied to a large extent by the recent development of methods for discriminating between the two species 1, 4, 10, 11, 13, 15; I. F. Salkin, W. R. Pruitt, A. A. Padhye, D. Sullivan, D. Coleman, and D. H. Pincus, Letter, J. Clin. Microbiol. 36:1467, 1998). Therefore, we agree with Dr. Meis and colleagues that efforts must be made to correctly identify germ-tube-positive yeast isolates, especially since the majority of blood culture isolates of C. dubliniensis (seven of eight) reported to date have been recovered from HIV-negative individuals.


    FOOTNOTES

    REFERENCES

1. Bikandi, J., R. San Millán, M. D. Moragues, G. Cebas, M. Clarke, D. C. Coleman, D. J. Sullivan, G. Quindós, and J. Pontón. 1998. Rapid identification of Candida dubliniensis by indirect immunofluorescence based on differential localization of antigens on C. dubliniensis blastospores and Candida albicans germ tubes. J. Clin. Microbiol. 36:2428-2433[Abstract/Free Full Text].
2. Brandt, M. E., L. H. Harrison, M. Pass, A. N. Sofair, S. H. Huie, R.-K. Li, C. J. Morrison, D. W. Warnock, and R. A. Hajjeh. 2000. Candida dubliniensis fungemia: the first four cases in North America. Emerg. Infect. Dis. 6:46-49.
3. Coleman, D. C., D. J. Sullivan, D. E. Bennett, G. P. Moran, H. J. Barry, and D. B. Shanley. 1997. Candidiasis: the emergence of a novel species, Candida dubliniensis. AIDS 11:557-567[CrossRef][Medline].
4. Donnelly, S. M., D. J. Sullivan, D. B. Shanley, and D. C. Coleman. 1999. Phylogenetic analysis and rapid identification of Candida dubliniensis based on analysis of ACT1 intron and exon sequences. Microbiology 145:1871-1882[Abstract/Free Full Text].
5. Jabra-Rizk, M. A., A. A. M. A. Baqui, J. I. Kelley, W. A. Falkler, Jr., W. G. Merz, and T. F. Meiller. 1999. Identification of Candida dubliniensis in a prospective study of patients in the United States. J. Clin. Microbiol. 37:321-326.
6. Kirkpatrick, W. R., S. G. Revankar, R. K. McAtee, J. L. Lopez-Ribot, A. W. Fothergill, D. I. McCarthy, S. E. Sanche, R. A. Cantu, M. G. Rinaldi, and T. F. Patterson. 1998. Detection of Candida dubliniensis in oropharyngeal samples from human immunodeficiency virus-infected patients in North America by primary CHROMagar Candida screening and susceptibility testing of isolates. J. Clin. Microbiol. 36:3007-3012[Abstract/Free Full Text].
7. Meis, J. F. G. M., M. Ruhnke, B. E. De Pauw, F. C. Odds, W. Siegert, and P. E. Verweij. 1999. Candida dubliniensis in patients with chemotherapy-induced neutropenia and bone marrow transplantation. Emerg. Infect. Dis. 5:150-153.
8. Moran, G. P., D. J. Sullivan, M. C. Henman, C. E. McCreary, B. J. Harrington, D. B. Shanley, and D. C. Coleman. 1997. 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. 41:617-623[Abstract].
9. Odds, F. C., L. Van Nuffel, and G. Dams. 1998. Prevalence of Candida dubliniensis isolates in a yeast stock collection. J. Clin. Microbiol. 36:2869-2873[Abstract/Free Full Text].
10. Pincus, D. H., D. C. Coleman, E. R. Pruitt, A. A. Padhye, I. F. Salkin, M. Geimer, A. Bassel, D. J. Sullivan, M. Clarke, and V. Hearn. 1999. Rapid identification of Candida dubliniensis with commercial yeast identification systems. J. Clin. Microbiol. 37:3533-3539[Abstract/Free Full Text].
11. Pinjon, E., D. Sullivan, I. Salkin, D. Shanley, and D. Coleman. 1998. Simple, inexpensive, reliable method for differentiation of Candida dubliniensis from Candida albicans. J. Clin. Microbiol. 36:2093-2095.
12. Polacheck, I., J. Strahilevitz, D. Sullivan, S. Donnelly, I. F. Salkin, and D. C. Coleman. 2000. Recovery of Candida dubliniensis from non-human immunodeficiency virus-infected patients in Israel. J. Clin. Microbiol. 38:170-174.
13. Sullivan, D., and D. Coleman. 1998. Candida dubliniensis: characteristics and identification. J. Clin. Microbiol. 36:329-334[Free Full Text].
14. Sullivan, D., K. Haynes, J. Bille, P. Boerlin, L. Rodero, S. Lloyd, M. Henman, and D. Coleman. 1997. Widespread geographic distribution of oral Candida dubliniensis strains in human immunodeficiency virus-infected individuals. J. Clin. Microbiol. 35:960-964[Abstract].
15. Sullivan, D. J., G. Moran, S. Donnelly, S. Gee, E. Pinjon, B. McCartan, D. B. Shanley, and D. C. Coleman. 1999. Candida dubliniensis: an update. Rev. Iberoam. Micol. 16:72-76.
16. Sullivan, D. J., T. J. Westerneng, K. A. Haynes, D. E. Bennett, and D. C. Coleman. 1995. Candida dubliniensis sp. nov.: phenotypic and molecular characterization of a novel species associated with oral candidosis in HIV-infected individuals. Microbiology 141:1507-1521.
17. Willis, A. M., W. A. Coulter, D. J. Sullivan, D. C. Coleman, J. R. Hayes, P. M. Bell, and P.-J. Lamey. 2000. Isolation of C. dubliniensis from insulin-using diabetes mellitus patients. J. Oral Pathol. Med. 29:86-90[CrossRef][Medline].
D. Coleman
Department of Oral Medicine and Pathology
School of Dental Science
University of Dublin
Trinity College
Dublin 2, Ireland


Journal of Clinical Microbiology, August 2000, p. 3139-3140, Vol. 38, No. 8
0095-1137/00/$04.00+0



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