Laboratory Diagnosis of Invasive Candidiasis

  • Ellepola Arjuna N.B. (Mycotic Diseases Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, of Oral Medicine and Periodontology, Faculty of Dental Sciences, University of Peradeniya) ;
  • Morrison Christine J. (Mycotic Diseases Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention)
  • Published : 2005.02.28

Abstract

Invasive candidiasis is associated with high morbidity and mortality. Clinical diagnosis is complicated by a lack of specific clinical signs and symptoms of disease. Laboratory diagnosis is also complex because circulating antibodies to Candida species may occur in normal individuals as the result of commensal colonization of mucosal surfaces thereby reducing the usefulness of antibody detection for the diagnosis of this disease. In addition, Candida species antigens are often rapidly cleared from the circulation so that antigen detection tests often lack the desired level of sensitivity. Microbiological confirmation is difficult because blood cultures can be negative in up to 50% of autopsy-proven cases of deep-seated candidiasis or may only become positive late in the infection. Positive cultures from urine or mucosal surfaces do not necessarily indicate invasive disease although can occur during systemic infection. Furthermore, differences in the virulence and in the susceptibility of the various Candida species to antifungal drugs make identification to the species level important for clinical management. Newer molecular biological tests have generated interest but are not yet standardized or readily available in most clinical laboratory settings nor have they been validated in large clinical trials. Laboratory surveillance of at-risk patients could result in earlier initiation of antifungal therapy if sensitive and specific diagnostic tests, which are also cost effective, become available. This review will compare diagnostic tests currently in use as well as those under development by describing their assets and limitations for the diagnosis of invasive candidiasis.

Keywords

References

  1. Abi-Said, D., E. Anaissie, O. Uzun, 1. Raad, H. Pinzcowski, and S. Vartivarian. 1997. The epidemiology of hematogenous candidiasis caused by different Candida species. Clin Infect Dis. 24, 1122-1128. Erratum in: Clin. Infect. Dis. 25, 352.
  2. AI Mosaid, A, J. Sullivan, and D.C. Coleman. 2003. Differentiation of Candida dubliniensis from Candida albicans on Pal's agar. J Clin. Microbiol. 41, 4787-4789.
  3. Araj, GF., RL. Hopfer, S. Chesnut, V. Fainstein, and GP. Bodey GP. 1982. Diagnostic value of the enzyme-linked immunosorbent assay for detection of Candida albicans cytoplasmic antigen in sera of cancer patients. J Clin. Microbiol. 16,46-52.
  4. Archibald, LX, t.c. McDonald, R.M. Addison, C. McKnight, T, Byrne, H. Dobbie, O. Nwanyanwu, P. Kazembe, L.B. Reller, and WR. Jarvis. 2000. Comparison of BACTEC MYCOIF Lytic and WAMPOLE ISOLATOR 10 (lysis-centrifugation) systems for detection of bacteremia, mycobacteremia, and fungemia in a developing country. J Clin. Microbiol. 38, 2994-2997.
  5. Bailey, 1.W, E. Sada, C. Brass, and 1.E. Bennett. 1985. Diagnosis of systemic candidiasis by latex agglutination for serum antigen. J Clin. Microbiol. 21, 749-752.
  6. Banerjee, S.N., TG Emori, D.H. Culver, R.P. Gaynes, W.R Jarvis, T. Horan, 1.R Edwards, J. Tolson, T Henderson, and WJ. Martone. 1991. Secular trends in nosocomial primary bloodstream infections in the United States, 1980-1989. National Nosocomial Infections Surveillance System. Am. J Med. 91, 86S-89S.
  7. Bar, W, and H. Hecker. 2002. Diagnosis of systemic Candida infections in patients of the intensive care unit. Significance of serum antigens and antibodies. Mycoses. 45, 22-28.
  8. Baumgartner, C; AM. Freydiere, and Y Gille. 1996. Direct identification and recognition of yeast species from clinical material by using Albicans ID and CHROMagar Candida plates. J Clin. Microbial. 34, 454-456.
  9. Bautista-Munoz, c, X.M. Boldo, L. ViIla-Tanaca, and C. Hernandez-Rodriguez. 2003. Identification of Candida spp. by randomly amplified polymorphic DNA analysis and differentiation between Candida albicans and Candida dubliniensis by direct PCR methods. J Clin. Microbiol. 41, 414-420.
  10. Berenguer, 1., M. Buck, F. Witebsky, F. Stock, P.A. Pizzo, and TJ. Walsh. 1993. Lysis-centrifugation blood cultures in the detection of tissue-proven invasive candidiasis. Diagn. Microbial. Infect. Dis. 17, 103-109.
  11. Bernal, S., E. Martin Mazuelos, M. Chavez, J. Coronilla, and A Valverde. 1998. Evaluation of the new API Candida system for identification of the most clinically important yeast species. Diagn. Microbiol. Infect. Dis. 32, 217-221.
  12. Bikandi, 1., RS. Millan, M.D. Moragues, G Cebas, M. Clarke, D.C. Coleman, DJ. Sullivan, G Quindos, and 1. Ponton. 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.
  13. Borst, A., B. Theelen, E. Reinders, T Boekhout, AC. Fluit, and P.H. Savelkoul. 2003. Use of amplified fragment length polymorphism analysis to identify medically important Candida spp., including C. dubliniensis. J Clin. Microbial. 41, 1357-1362.
  14. Boucher, H., S. Mercure, S. Montplaisir, and G Lemay. 1996. A novel group I intron in Candida dubliniensis is homologous to a Candida albicans intron. Gene. 180, 189-196.
  15. Bougnoux, M.E., C. Hill, D. Moissenet, M. Feuilhade de Chauvin, M. Bonnay, I. Vicens-Sprauel, F. Pietri, M. McNeil, L. Kaufman, and J. Dupouy-Camet. 1990. Comparison of antibody, antigen, and metabolite assays for hospitalized patients with disseminated or peripheral candidiasis. J Clin. Microbiol. 28, 905-909.
  16. Buchman, TG, M. Rossier, WG Merz, and P. Charache. 1990. Detection of surgical pathogens by in vitro DNA amplification. Part I. Rapid identification of Candida albicans by in vitro amplification of a fungus-specific gene. Surgery. 108,338-347.
  17. Burgener-Kairuz, P., J.P. Zuber, P. Jaunin, TG Buchman, J. Bille, and M. Rossier. 1994. Rapid detection and identification of Candida albicans and Torulopsis (Candida) glabrata in clinical specimens by species-specific nested PCR amplification of a cytochrome P-450 lanosterol-a-demethylase (L1AI) gene fragment. J Clin. Microbiol. 32, 1902-1907.
  18. Burnie, 1.P. 1985. A reverse passive latex agglutination test for the diagnosis of systemic candidiasis. J Immunol. Methods. 82, 267-280.
  19. Campbell, C.K, KG Davey, AD. Holmes, A Szekely, and D.W Warnock. 1999. Comparison of the API Candida system with the AUXACOLOR system for identification of common yeast pathogens. J Clin. Microbiol. 37, 821-823.
  20. Centers for Disease Control and Prevention. 2000. Monitoring hospital acquired infections to promote patient safety in the United States, 1990-1999. Morb. Mortal Wkly Rep. 49, 149-153.
  21. Chen, Yc., J.D. Eisner, M.M. Kattar, S.L. Rassoulian-Barrett, K LaFe, S.L. Yarfitz, AP. Limaye, and BT. Cookson. 2000. Identification of medically important yeasts using PCR-based detection of DNA sequence polymorphisms in the internal transcribed spacer 2 region of the rRNA genes. J Clin. Microbiol. 38, 2302-2310
  22. Christensson, B., G Sigmundsdottir, and L. Larsson. 1999. Darabinitol-a marker for invasive candidiasis. Med. Mycol. 37, 391-396.
  23. Cirak, MY, A Kalkanci, and S. Kustimur. 2003. Use of molecular methods in identification of Candida species and evaluation of fluconazole resistance. Mem. Inst. Oswaldo. Cruz. 98, 1027-1032.
  24. Coignard, c. S.F. Hurst, L.E. Benjamin, M.E. Brandt, D.W Warnock, and CJ. Morrison. 2004. Resolution of discrepant results for Candida species identification by using DNA probes. J Clin. Microbiol. 42, 858-861.
  25. Crampin, AC. and R.C. Matthews. 1993. Application of the polymerase chain reaction to the diagnosis of candidosis by amplification of an HSP 90 gene fragment. J Med. Microbiol. 39, 233-238.
  26. Creger, RJ., KE. Weeman, M.R. Jacobs, A. Morrissey, P. Parker, RM. Fox, and H.M. Lazarus. 1998. Lack of utility of the Iysiscentrifugation blood culture method for detection of fungemia in immunocompromised cancer patients. J Clin. Microbiol. 36, 290-293.
  27. Davey, KG, P.M. Chant, C.S. Downer, CX Campbell, and D.W Warnock. 1995. Evaluation of the AUXACOLOR system, a new method of clinical yeast identification. J Clin. Pathol. 48, 807-809.
  28. De Caux, B.S., D. Thomas, PJ. Stephens, and C. Booth. 2004. Clinical evaluation of a new selective and differential medium for the rapid isolation and presumptive identification of Candida species. Abstr. C-I04, p. 141. Abstr. 104lh Annu. Meet. Am. Soc. Microbiol.
  29. Denning, D.W, c.c. Kibbler, and R.A. Barnes. 2003. British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections. Lancet Infect. Dis. 3, 230-240.
  30. De Repentigny, L., L.D. Marr, J.W Keller, A.W Carter, RJ. Kuykendall, L. Kaufman, and E. Reiss. 1985. Comparison of enzyme immunoassay and gas-liquid chromatography for the rapid diagnosis of invasive candidiasis in cancer patients. J Clin. Microbiol. 21, 972-979.
  31. Doem, GY., A Barton, and S. Rao. 1998. Controlled comparative evaluation of BacT/Alert FAN and ESP 80A aerobic media as means for detecting bacteremia and fungemia. J Clin. Microbial. 36, 2686-2689.
  32. Donnelly, S.M., DJ. Sullivan, D.B. Shanley, and D.C. Coleman. 1999. Phylogenetic analysis and rapid identification of Candida dubliniensis based on analysis of ACT] intron and exon sequences. Microbiol. 145, 1871-1882.
  33. Edmond, M.B., S.E. Wallace, D.K. McClish, M.A. Pfaller, R.N. Jones, and RP. Wenzel. 1999. Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin. Infect. Dis. 29, 239-244.
  34. Edwards Jr, J.E. 1992. Should all patients with candidemia be treated with antifungal agents? Clin. Infect. Dis. 15,4222-4223.
  35. Einsele, H., H. Hebart, G Roller, J. Loffler, I. Rothenhofer, C.A. Muller, RA Bowden, J. van Burik, D. Engelhard, L. Kanz, and U. Schumacher. 1997. Detection and identification of fungal pathogens in blood by using molecular probes. J Clin. Microbiol. 5, 1353-1360.
  36. Elie, C.M., T.J. Lott, E. Reiss, and CJ. Morrison. 1998. Rapid identification of Candida species using species-specific DNA probes. J Clin. Microbiol. 36, 3260-3265.
  37. Ellepola, AN., S.F. Hurst, C.M. Elie, and c.r. Morrison. 2003. Rapid and unequivocal differentiation of Candida dubliniensis from other Candida species using species-specific DNA probes: comparison with phenotypic identification methods. Oral. Microbiol. Immunol. 18, 379-388.
  38. El Moudni, B., M.H. Rodier, G Daniault, and J.L. Jacquemin. 1998. Improved immunodiagnosis of human candidiasis by an enzyme-linked immunosorbent assay using a Candida albicans 52-kilodalton metallopeptidase. Clin. Diagn. Lab. Immunol. 5, 823-825.
  39. Espinel-Ingroff, A, L. Stockman, G Roberts, D. Pincus, J. Pollack, and J. Marler. 1998. Comparison of RapID Yeast Plus system with API 20C system for identification of common, new, and emerging yeast pathogens. J Clin. Microbiol. 36, 883-886.
  40. Flahaut, M., D. Sanglard, M. Monod, J. Bille, and M. Rossier. 1998. Rapid detection of Candida albicans in clinical samples by DNA amplification of common regions from C. albicanssecreted aspartic proteinase genes. J Clin. Microbiol. 36, 395401.
  41. Freydiere, AM. 1996. Evaluation of CHROMagar Candida plates. J Clin. Microbiol. 34, 2048.
  42. Freydiere, AM., L. Buchaille, and Y. Gille. 1997a. Comparison of three media for direct identification and discrimination of Candida species in clinical specimens. Eur. J. Clin. Microbiol. Infect. Dis. 16,464-467.
  43. Freydiere, A.M., L. Buchaille, R Guinet, and Y. Gille. 1997b. Evaluation of latex reagents for rapid identification of Candida albicans and C. krusei colonies. J Clin. Microbiol. 35, 877-880.
  44. Freydiere, AM., R Guinet, and P. Boiron. 2001. Yeast identification in the clinical microbiology laboratory: phenotypical methods. Med. Mycol. 39, 9-33.
  45. Fujita, S., F. Matsubara, and T. Matsuda. 1986. Enzyme-linked immunosorbent assay measurement of fluctuations in antibody titer and antigenemia in cancer patients with and without candidiasis. J Clin. Microbiol. 23, 568-575.
  46. Fujita, S.l., B.A Lasker, TJ. Lott, E. Reiss, and CJ. Morrison. 1995. Microtitration plate enzyme immunoassay to detect PCR-amplified DNA from Candida species in blood. J Clin. Microbial. 33, 962-967.
  47. Fujita, S.I. and T. Hashimoto. 1992. Detection of serum Candida antigens by enzyme-linked immunosorbent assay and a latex agglutination test with anti-Candida albicans and anti-Candida krusei antibodies. J Clin. Microbiol. 30, 3131-3137.
  48. Fuller, D.D., T.E. Davis Jr, GA Denys, and M.K York. 2001. Evaluation of BACTEC MYCOIF Lytic medium for recovery of mycobacteria, fungi, and bacteria from blood. J Clin. Microbiol. 39, 2933-2936.
  49. Gentry, L.O., I.D. Wilkinson, AS. Lea, and M.F. Price. 1983. Latex agglutination test for detection of Candida antigen in patients with disseminated disease. Eur J Clin. Microbiol. Infect. Dis. 3, 122-128.
  50. Graf, B., A Trost, J. Eucker, U.B. Gobel, and T. Adam. 2004. Rapid and simple differentiation of C. dubliniensis from C. albicans. Diagn. Microbiol. Infect. Dis. 48, 149-151.
  51. Greenfield, RA, MJ. Bussey, J.L Stephens, and J.M. Jones. 1983. Serial enzyme-linked immunosorbent assay for antibody to Candida antigens during induction chemotherapy for acute leukemia. J Infect. Dis. 148, 275-283.
  52. Greenfield, R.A. and J.M. Jones. 1981. Purification and characterization of a major cytoplasmic antigen of Candida albicans. Infect. Immun. 34,469-477.
  53. Gud1augsson, 0., S. Gillespie, K Lee, J. Vande Berg, J. Hu, S. Messer, L. Herwaldt, M. Pfaller, and D. Diekema. 2003. Attributable mortality of nosocomial candidemia, revisited. Clin. Infect Dis. 37, 1172-1177.
  54. Guiver, M., K Levi, and B.A Oppenheim. 2001. Rapid identification of Candida species by TaqMan PCR J Clin. Pathol. 54, 362-366.
  55. Hajjeh, RA, AN. Sofair, L.H. Harrison, GM. Lyon, B.A. Arthington-Skaggs, S.A Mirza, M. Phelan, J. Morgan, W. Lee-Yang, M.A. Ciblak, L.E. Benjamin, L.T. Sanza, S. Huie, S.F. Yeo, M.E. Brandt, and D.W. Wamock. 2004. Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J Clin. Microbiol. 42, 1519-1527.
  56. Hall, L., S. Wohlfiel, and GO. Roberts. 2003. Experience with the MicroSeq D2 large-subunit ribosomal DNA sequencing kit for identification of commonly encountered, clinically important yeast species J. Clin. Microbiol. 41, 5099-5102.
  57. Haynes, KA, TJ. Westemeng, J.W Fell, and W. Moens. 1995. Rapid detection and identification of pathogenic fungi by polymerase chain reaction amplification of large subunit ribosomal DNA.! Med. Vet. Mycol. 33, 319-325.
  58. Heelan, J.S., E. Sotomayor, K Coon, and J.B. D' Arezzo. 1998. Comparison of the rapid yeast plus panel with the API20C yeast system for the identification of clinically significant isolates of Candida species . .I Clin. Microbiol. 36, 1443-1445.
  59. Holmes, AR., R.D. Cannon, M.G Shepherd, and H.F. Jenkinson. 1994. Detection of Candida albicansesui other yeasts in blood by PCR J Clin. Microbiol. 32, 228-231.
  60. Hopfer, RL., P. Walden, S. Setterquist, and WE. Highsmith. 1993. Detection and differentiation of fungi in clinical specimens using polymerase chain reaction (PCR) amplification and restriction enzyme analysis. J Med. Vet. Mycol. 31, 65-75.
  61. Hoppe, J.E. and P. Frey. 1999. Evaluation of six commercial tests and the germ tube test for presumptive identification of Candida albicans. Eur. J Clin. Microbiol. Infect. Dis. 18, 188-191.
  62. Horvath, L.L., B.I. George, CK Murray, L.S. Harrison, and D.R. Hospenthal. 2004. Direct comparison of the BACTEC 9240 and BacT/ALERT 3D automated blood culture systems for Candida growth detection. J Clin. Microbiol. 42, 115-118.
  63. Hsu, M.C., KW Chen, H.I. Lo, Y.c. Chen, M.H. Liao, Y.H. Lin, and S.Y. Li. 2003. Species identification of medically important fungi by use of real-time LightCycler PCR. J Med. Microbiol. 52, 1071-1076.
  64. Hube, B. 1996. Candida albicans secreted aspartyl proteinases. Curro Top. Med. Mycol. 7, 55-69.
  65. Hui, M., M. Ip, P.K Chan, M.L. Chin, and AF. Cheng. 2000. Rapid identification of medically important Candida to species level by polymerase chain reaction and single-strand conformational polymorphism. Diagn. Microbiol. Infect. Dis. 38, 95-99.
  66. Irobi, J., A Schoofs, and H. Goossens. 1999. Genetic identification of Candida species in HIV-positive patients using the polymerase chain reaction and restriction fragment length polymorphism analysis of its DNA Mol. Cell. Probes. 13,401-406.
  67. Iwasaki, H., H. Misaki, T. Nakamura, and T. Ueda. 2000. Surveillance of the serum Candida antigen titer for initiation of antifungal therapy after post-remission chemotherapy in patients with acute leukemia. Intl. J Hematol. 71, 266-272.
  68. Iwen, ac, AG Freifeld, TA Bruening, and S.H. Hinrichs. 2004. Use of a panfungal PCR assay for detection of fungal pathogens in a commercial blood culture system. J Clin. Microbiol. 42, 2292-2293.
  69. Jabra-Rizk, M.A, T.M. Brenner, M. Romagnoli, AA Baqui, WG Merz, WA Falkler Jr, and T.E Meiller. 2001. Evaluation of a reformulated CHROMagar Candida. J Clin. Microbiol. 39, 2015-2016.
  70. Jaeger, E.E., N.M. Carroll, S. Choudhury, AA Dunlop, H.M. Towler, M.M. Matheson, P. Adamson, N. Okhravi, and S. Lightman. 2000. Rapid detection and identification of Candida, Aspergillus, and Fusarium species in ocular samples using nested peR. J Clin. Microbiol. 38, 2902-2908.
  71. Jones, J.M. 1980a. Kinetics of antibody responses to cell wall mannan and a major cytoplasmic antigen of Candida albicans in rabbits and humans. J Lab. Clin. Med. 96, 845-860.
  72. Jones, J.M. 1980b. Quantitation of antibody against cell wall mannan and a major cytoplasmic antigen of Candida in rabbits, mice, and humans. Infect. Immun. 30, 78-89.
  73. Jordan, J. 1994. PCR identification of four medically important Candida species by using a single primer pair. J Clin. Microbioi. 32, 2962-2967.
  74. Kahn, EW and J.M. Jones. 1986. Latex agglutination tests for detection of Candida antigens in sera of patients with invasive candidiasis. J Infect. Dis. 153, 579-585.
  75. Kaufman, L., J.A Kovacs, and E. Reiss. 1997. Clinical Immunomycology, p. 585-604. In N.R. Rose, s.c de Macario, J.D. Folds, H.c. Lane, and R.M. Nakamura (eds.), Manual of Clinical Laboratory Immunology. ASM Press, Washington, D.C.
  76. Kitch, T.T., M.R. Jacobs, M.R. McGinnis, and P.c. Appelbaum. 1996. Ability of RapID Yeast Plus System to identify 304 clinically significant yeasts within 5 hours. J Clin. Microbiol. 34, 1069-1071.
  77. Kurtzman, c.P. and C.I. Robnett. 1997. Identification of clinically important ascomycetous yeasts based on nucleotide divergence in the 5' end of the large-subunit (26S) ribosomal DNA gene. J Clin. Microbiol. 35, 1216-1223.
  78. Kurzai, 0., W.I. Heinz, D.I. Sullivan, D.C. Coleman, M. Frosch, and FA Muhlschlegel. 1999. Rapid PCR test for discriminating between Candida albicans and Candida dubliniensis isolates using primers derived from the pH-regulated PHRI and PHR2 genes of C. albicans. J Clin. Microbiol. 37, 1587-1590.
  79. Kwok, S. and R. Higuchi. 1989. Avoiding false positives with PCR. Nature 339, 237-238.
  80. Kwon-Chung, KJ., D. Lehman, C. Good, and P.T. McGee. 1985. Genetic evidence for role of extracellular proteinase in virulence of Candida albicans. Infect. Immun. 49, 571-575.
  81. Land, GA., I.E Salkin, M. EI-Zaatari, M.R. McGinnis, and 0. Hashem. 1991. Evaluation of the Baxter MicroScan 4-hour enzyme-based yeast identification system. J Clin. Microbiol. 29, 718-722.
  82. Lecciones, lA, lW Lee, E.E. Navarro, EO. Witebsky, D. Marshall, S.M. Steinberg, PA Pizzo, and T.I. Walsh. 1992. Vasculm; catheter-associated fungemia in patients with cancer: analysis of 155 episodes. Clin. Infect. Dis. 14,875-883.
  83. Lemieux, C; 0. St-Germain, J. Vincelette, L. Kaufman, and L. de Repentigny. 1990. Collaborative evaluation of antigen detection by a commercial latex agglutination test and enzyme immunoassay in the diagnosis of invasive candidiasis. J Clin. Microbiol. 28, 249-253.
  84. Lischewski, A, M. Kretschman, H. Hof, R. Amann, J. Hacker, and J. Morschhauser. 1997. Detection and identification of Candida species in experimentally infected tissue and human blood by rRNA-specific fluorescent in situ hybridization. J Clin. Microbioi. 35, 2943-2948.
  85. Loeffler, J., C. Dorn, H. Hebart, P. Cox, S. Magga, and H. Einsele. 2003. Development and evaluation of the nuclisens basic kit NASBA for the detection of RNA from Candida species frequently resistant to antifungal drugs. Diagn. Microbiol. Infect. Dis. 45, 217-220.
  86. Loeffler, J., H. Hebart, S. Magga, D. Schmidt, L. Klingspor, l Tollernar, U. Schumacher, and H. Einsele. 2000a. Identification of rare Candida species and other yeasts by polymerase chain reaction and slot blot hybridization. Diagn. Microbiol. Infect. Dis. 38, 207-212.
  87. Loeffler, J., H. Hebart, S. Sepe, U. Schumacher, T. Klingbiel, and J. Einsele. 1998. Detection of PCR-amplified fungal DNA by using a PCR-ELISA system. Med. Mycol. 36, 275-279.
  88. Loeffler, J., N. Henke, H. Hebart, D. Schmidt, L Hagmeyer, U. Schumacher, and H. Einsele H. 2000b. Quantification of fungal DNA by using fluorescence resonance energy transfer and the light cycler system. J Clin. Microbiol. 38, 586-590.
  89. MacDonald, F. and EC. Odds. 1983. Virulence for mice of a proteinase-secreting strain of Candida albicans and a proteinasedeficient mutant. J Gen. Microbiol. 129,431-438.
  90. Mannarelli, B.M. and CP Kurtzman. 1998. Rapid identification of Candida albicans and other human pathogenic yeasts by using short oligonucleotides in a PCR. J Clin. Microbiol. 36, 1634-1641.
  91. Martin. c, D. Roberts, M. van Der Weide, R Rossau, 0. Jannes, T Smith, and M. Maher. 2000. Development of a PCR-based line probe assay for identification of fungal pathogens. J Clin. Microbiol. 38, 3735-3742.
  92. Mason, A.B., ME Brandt, and H.R. Buckley. 1989. Enolase activity associated with a Candida albicans cytoplasmic antigen. Yeast 5, S231-239..
  93. Massonet, c, 1 Van Eldere, M. Vaneechoutte, T De Baere, J. Verhaegen, and K. Lagrou. 2004. Comparison of VITEK 2 with ITS2-fragment length polymorphism analysis for identification of yeast species. J Clin. Microbiol. 42, 2209-2211.
  94. Matthews, R.J. and J.P. Burnie. 1988. Diagnosis of systemic candidiasis by an enzyme-linked dot immunobinding assay for a circulating immunodominant 47-kiloda1ton antigen. J Clin. Microbiol. 26, 459-463.
  95. Matthews, R.J., lP. Burnie, and S. Tabagchali. 1987. Isolation of immunodominant antigens from sera of patients with systemic candidiasis and characterization of serological response to Candida albicans. J Clin. Microbiol. 25, 230-237.
  96. McDonald, t.c, M.P. Weinstein, J. Fune, S. Mirrett, L.G Reimer, and L.B. Reller. 2001. Controlled comparison of BacT/ALERT FAN aerobic medium and BACTEC fungal blood culture medium for detection of fungemia. J Clin. Microbiol. 39, 622624.
  97. Misaki, H., H. Iwasaki, and T Ueda. 2003. A comparison of the specificity and sensitivity of two Candida antigen assay systems for the diagnosis of deep candidiasis in patients with hematologic diseases. Med. Sci. Monit. 9, MTI-7.
  98. Miyakawa, Y., T Mabuchi, and Y. Fukazawa. 1993. New method for detection of Candida albicans in human blood by polymerase chain reaction. J Clin. Microbiol. 31, 3344-3347.
  99. Moghaddas, r., AL. Truant, e. Jordan, and H.R. Buckley. 1999. Evaluation of the RapID Yeast Plus System for the identification of yeast. Diagn. Microbiol. Infect. Dis. 35, 271-273.
  100. Morace, 0., M. Sanguinetti, B. Posteraro, 0. LoCascio, and 0. Fadda. 1997. Identification of various medically important Candida species in clinical specimens by PCR-restriction enzyme analysis. J Clin. Microbiol. 35, 667-672.
  101. Moran, GP., D. Sanglard, S.M. Donnelly, D.B. Shanley, DJ. Sullivan, and D.e. Coleman. 1998. Identification and expression of multidrug transporters responsible for fluconazole resistance in Candida dubliniensis. Antimicrob. Agents Chemother. 42, 1819-1830.
  102. Moran, GP., DJ. Sullivan, M.e. Henman, c.n McCreary, BJ. Harrington,D.H. Shanley, and D.C. Coleman. 1997. Antifungal rug susceptibilities of oral Candida dubliniensis isolates from uman immunodeficiency virus (HIV)-infected and non-Hl'Vinfected subjects and generation of stable fluconazole-resi~tant derivatives in vitro. Antimicrob. Agents Chemother. 41, 617- 623.
  103. Morrison, CJ., S.F. Hurst, and E. Reiss. 2003. Competitive binding inhibition enzyme-linked imrnunosorbent assay that uses the secreted aspartyl proteinase of Candida albicans as an antigenic Diagn. Lab. Immunol. 10, 835-848.
  104. Na, B.K. and CY Song. 1999. Use of monoclonal antibody in diagnosis of candidiasis caused by Candida albicans: detection of circulating aspartyl proteinase antigen. Clin. Diagn. Lab. Immunol. 6, 924-929.
  105. Nguyen, M.H, J.E. Peacock Jr, A.J. Morris, D.C. Tanner, M.L. Nguyen, D.R Snydman, M.M. Wagener, M.G Rinaldi, and V.L. Yu. 1996. The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance. Am J Med. 100,617-623.
  106. Obayashi, T., M. Yoshida, T Mori, H. Goto, A Yasuoka, H. Iwasaki, H. Teshima, S. Kohno, A. Horiuchi, and A Ito. 1995. Plasma (I-73)-beta-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes. Lancet. 345, 17-20.
  107. Obayashi, T, M. Yoshida, H. Tamura, J. Aketagawa, S. Tanaka, and Kawai T. 1992. Determination of plasma (I-73)-~-D-glucan: a new diagnostic aid to deep mycosis. J Med. Vet. Mycol. 30, 275-280.
  108. Odabasi, Z., 0. Mattiuzzi, L. Ostrosky-Zeichner, E. Estey, H. Kantarjian, and J.H. Rex. 2002. Detection of (1-73)-~-D-Glucan in the serum of leukemia patients with invasive fungal infections. Abstr. M-902, p. 396. Abstr. 42nd ICAAC.
  109. Odds, F. and R. Bernaerts. 1994. CHROMagar Candida, a new differential medium for presumptive identification of clinically important Candida species. J Clin. Microbial. 12, 1923-1929.
  110. Oliveira, K., 0. Haase, e. Kurtzman, lJ. Hyldig-Nielsen, and H. tender. 2001. Differentiation of Candida albicans and Candida nucleic acid probes. J Clin. Microbiol. 39,4138-4141.
  111. Pallavicini, F., 1. Izzi, MA Pennisi, 0. Morace, Go. Portaccio, 0. Bello, F. Iodice, D. Godino, e. Del Borgo, and R. Proietti. 1999. Evaluation of the utility of serological tests in the diagnosis of candidemia. Minerva Anestesiologica. 65, 637-639.
  112. Pappas, ro. J.H. Rex, lD. Sobel, S.G Filler, W.E. Dismukes, TJ. Walsh, and lE. Edwards. 2004. Guidelines for treatment of candidiasis. Clin. Infect. Dis. 15, 161-189.
  113. Patterson, TF., S.G Revankar, W.R. Kirkpatrick, RK. McAtee, AW. Fothergill, DJ. McCarthy, and M.G Rinaldi. 1996. Simple method for detecting fluconazole-resistant yeasts with chromogenic agar. J Clin. Microbiol. 34, 1794-1797.
  114. Petti, c.x., A.K. Zaidi, S. Mirrett, and L.B. Reller. 1996. Comparison of Isolator 1.5 and BACTEC NR660 aerobic 6A blood culture systems for the detection of fungemia in children. J au: Microbiol. 34, 1877-1879.
  115. Pfaller, M.A, A Houston, and S. Coffmann. 1996. Application of CHROMagar Candida for rapid screening of clinical specimens for Candia albicans, Candida tropicalis, Candida krusei, and Candida (Torulopsis) glabrata. J Clin. Microbiol. 34, 58-61.
  116. Pfaller, MA, SA Messer, S. Gee, S. Joly, e. Pujol, DJ. Sullivan, D.C. Coleman, and D.R. Soil. 1999. In vitro susceptibilities of Candida dubliniensis isolates tested against the new tiiazole and echinocandin antifungal agents. J Clin. Microbiol. 37, 870872.
  117. Phillips, P., A Dowd, P. Jewesson, 0. Radigan, M.G Tweeddale, A Clarke, 1. Geere, and M.. Kelly. 1990. Nonvalue of antigen detection immunoassays for diagnosis of candidemia. J Clin. Microbiol. 28, 2320-2326.
  118. Posteraro, B., M. Sanguinetti, L. Masucci, L. Romano, 0. Morace, and 0. Fadda. 2000. Reverse cross blot hybridization assay for rapid detection of PCR-amplified DNA from Candida spcceis, Cryptococcus neoformans, and Saccharomyces cerevisiae in clinical samples. J cu« Microbiol. 38, 1609-1614.
  119. Powell, H.L., e.A Sand, and RP. Rennie. 1998. Evaluation of CHROMagar Candida for presumptive identification of clinically important Candida species. Diagn. Microbial. Infect Dis. 32, 201-204.
  120. Price, M.F, M.T. LaRocco, and L.O. Gentry. 1994. Fluconazole susceptibilitiesof Candida species and distribution of species recovered from blood cultures over a 5-year period. Antimicrob. Agents Chemother. 38, 1422-1424.
  121. Procop, GW., FR. Cockerill 3rd, E.A. Vetter, W.S. Harmsen, 1.0. Hughes, and GO. Roberts. 2000. Performance of five agar media for recovery of fungi from isolator blood cultures. J Clin. Microbiol. 38. 3827-3829.
  122. Pryce, T.M., 1.0. Kay, S. Palladino, and CH. Heath. 2003. Realtime automated polymerase chain reaction (PCR) to detect Candida albicans and Aspergillus fumigatus DNA in whole blood from high-risk patients. Diagn. Microbiol. Infect Dis. 47, 487-496.
  123. Quindos, 0., R. San Millan, R Robert, C Bernard, and J. Poton. 1997. Evaluation of Bichro-Iatex albicans, a new method for rapid identification of Candida albicans. J Clin. Microbiol. 35, 1263-1265.
  124. Quindos, 0., V. Lipperheide, and J. Ponton. 1993. Evaluation of two commercialized systems for the rapid identification of medically important yeasts. Mycoses. 36, 299-303.
  125. Rabkin, J.M., S.L. Oroloff, C.L. Corless, K.G Benner, KD. Flora, H.R Rosen, and A.J. Olyaei. 2000. Association of fungal infection and increased mortality in liver transplant recipients. Am J Surg. 179,426-430.
  126. Rabkin, J.M., S.L. Oroloff, C.L. Corless, K.G Benner, KD. Flora, H.R Rosen, and A.J. Olyaei. 2000. Association of fungal infection and increased mortality in liver transplant recipients. Am J Surg. 179,426-430.
  127. Ray, T.L. and CD. Payne. 1988. Scanning electron microscopy of epidermal adherence and cavitation in murine candidiasis: a role for Candida acid proteinase. Infect. Immun. 56, 19421949.
  128. Ray, T.L., CD. Payne, and B.J. Morrow. 1991. Candida acid proteinases: characterization and role in candidiasis. Adv. Exp. Med. Bioi. 306, 173-183.
  129. Rees, 1.R, R.W Pinner, RA Hajjeh, M.E. Brandt, and AL. Reingold. 1998. The epidemiological features of invasive mycotic infections in the San Francisco Bay area, 1992-1993: results of population-based laboratory active surveillance. Clin. Infect. Dis. 27, 1138-1147.
  130. Reimer, L.G, M.L. Wilson, and M.P. Weinstein. 1997. Update on detection of bacteremia and fungemia. Clin. Microbiol. Rev. 10, 444-465.
  131. Reiss, E. and C.J. Morrison. 1993. Nonculture methods for the diagnosis of Candida infections. Clin. Microbiol. Rev. 6, 311-323.
  132. Rex JH, Bennett JE, Sugar AM, P.G Pappas, CM. van der Horst, 1.E. Edwards, RG Washburn, WM. ScheId, A.W Karchmer, and A.P. Dine. 1994. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. N Eng. J Med. 331; 1325-1330.
  133. Rigby, S., GW Procop, 0. Haase, D. Wilson, 0. Hall, C Kurtzman, K Oliveira, S. Von Oy, 1.1. Hyldig-Nielsen, 1. Coull, and H. Stender. 2002. Fluorescence in situ hybridization with peptide nucleic acid probes for rapid identification of Candida albicans directly from blood culture bottles. J Clin. Microbiol. 40,21822186.
  134. Rigby, S., GW Procop, 0. Haase, D. Wilson, 0. Hall, C Kurtzman, K Oliveira, S. Von Oy, 1.1. Hyldig-Nielsen, 1. Coull, and H. Stender. 2002. Fluorescence in situ hybridization with peptide nucleic acid probes for rapid identification of Candida albicans directly from blood culture bottles. J Clin. Microbiol. 40,21822186.
  135. Ruchel, Rand B. Boning-Stutzer. 1983. Detection of Candida pro-teinase by enzyme immunoassay and interaction of the enzyme with alpha-2-macroglobulin. J Immunol. Methods. 61, 107-116.
  136. Ruchel, R., B. Boning-Stutzer, and A. Mari. 1988. A synoptical approach to the diagnosis of candidosis, relying on serological antigen and antibody tests, on culture, and on evaluation of clinical data. Mycoses: 31, 87-106.
  137. Ruchel, R., B. Boning-Stutzer, and A. Mari. 1988. A synoptical approach to the diagnosis of candidosis, relying on serological antigen and antibody tests, on culture, and on evaluation of clinical data. Mycoses: 31, 87-106.
  138. Sandhu" 0., B.C Kline, L. Stockman, and GO. Roberts. 1995. Molecular probes for diagnosis of fungal infections. J Clin. Microbial. 33, 2913-2919.
  139. San-Millan, R, L. Ribacoba, J. Ponton, and 0. Quindos. 1996. Evaluation of a commercial medium for identification of Candida species. Eur. J Clin. Microbiol. Infect Dis. 15, 153-158.
  140. Schmidt, D., 1. Loeffler, H. Hebart, U. Schumacher, and H. Einsele. 2001. Rapid extraction and detection of DNA from Candida species in research samples by MagNA Pure LC and the light cycler. Biochemica. 3, 1-3.
  141. Selvarangan, R,' U. Bui, AP. Limaye, and B.T. Cookson. 2003. Rapid identification of commonly encountered Candida species directly from blood culture bottles. J'Clin. Microbiol. 41, 5660-5664.
  142. Selvarangan, R, AP. Limaye, and B.T. Cookson. 2002. Rapid identification and differentiation of Candida albicans and Candida dubliniensis by capillary-based amplification and fluorescent probe hybridization. .I Clin. Microbiol. 40, 4308-4312.
  143. Sendid, B., T. Jouault, R Coudriau, D. Camus, F Odds, M. Tabouret, and D. Poulain. 2004. Increased sensitivity of mannanemia detection tests by joint detection of o- and ~-linked oligornannosides during experimental and' human systemic candidiasis. J Clin. Microbiol. 42, 164-171.
  144. Sendid, B., M. Tabouret, 1.L. Poirot, D. Mathieu, J. Fruit, and D. Poulain. 1999. New enzyme immunoassays for sensitive detection of circulating Candida albicans mannan and antimannan antibodies: useful combined test for diagnosis of systemic candidiasis. J Clin. Microbiol. 37, 1510-1517
  145. Shin, 1.H., FS. Nolte, and C.J. Morrison. 1997. Rapid identification of Candida species in blood cultures by a clinically useful PCR method. J Clin. Microbiol. 35, 1454-1459.
  146. Shin, 1.H., FS. Nolte, and C.J. Morrison. 1999. Rapid identification of up to three Candida species in a single reaction tube by a 5' exonuclease assay using fluorescent DNA probes. J Clin. Microbiol. 37, 165-170.
  147. Staib, F 1965. Serum-proteins as nitrogen source for yeast-like fungi. Sabouraudia. 4, 187-193.
  148. Stevens, P., S. Huang, L.S. Young, aJld M. Berdischewsky. 1980. Detection of Candida antigenemia in human invasive candidiasis by a new solid phase radioimmunoassay. Infection. 8, S334-338.
  149. St-Germain, 0. and D. Beauchesne. 1991. Evaluation of the MicroScan rapid yeast identification panel. J Clin. Microbiol. 29, 2296-2299.
  150. Strockbine, N.A, M.T. Largen, and H.R Buckley. 1984a. Production and characterization of three monoclonal antibodies to Candida albicans proteins. Infect. Immun, 43, 1012-1018.
  151. Strockbine, N.A, M.T. Largen, S.M. Zweibel, and H.R. Buckley. 1984b. Identification and molecular weight characterization of antigens from Candida albicans that are recognized by human sera. Infect. Immun. 43, 715-721.
  152. Sundstrom, P. and GR Aliaga. 1992. Molecular cloning of cDNA and analysis of protein secondary structure of Candida albicans enolase, an abundant, immunodominant glycolytic enzyme. J Bacteriol. 174, 6789-6799.
  153. Switchenko, AC., c.o Miyada, TC. Goodman, T.J. Walsh, B. Wong, M.J. Becker, and EF. Ullman. 1994. An automated enzymatic method for measurement of D-arabinitol, a metabolite of pathogenic Candida species. J Clin. Microbiol. 32, 9297.
  154. Takesue, Y.,M. Kakehashi, H. Ohge, Y. Imamura, Y. Murakami, M. Sasaki, M. Morifuji, Y. Yokoyama, M. Kouyama, T Yokoyama, and T. Sueda. 2004. Combined Assessment of $\beta$-dGlucan and Degree of Candida Colonization before Starting Empiric Therapy for Candidiasis in Surgical Patients. World J Surg. In press.
  155. Tamura, H., Y. Arimoto, S-. Tanaka, M. Yoshida, T. Obayashi, and T Kawai. 1994. Automated kinetic assay for endotoxin and (I$\longrightarrow$3)-$\beta$-D-glucanin human blood. Clin Chim Acta. 226, 109112.
  156. Tiraboschi, 1.N., J.E. Bennett, C.A. Kaufmann, J.H. Rex, e. Girmenia, .D. Sobel, and F. Menichetti. 2000. Deep Candida nfections in the neutropenic and non-neutropenic host: an ISHAM symposium. Med. Mycol. 38, 199-204.
  157. Trick, WE., S.K. Fridkin, J.R Edwards, RA Hajjeh, and RP. Gaynes. 2002. Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989-1999. Clin. Infect. Dis. 35, 627-630.
  158. van Deventer, A.J., W.H. Goessens, A van Belkum, H.J. van Vliet, EW. van Etten, and H.A Verbrugh. 1995. Improved detection of Candida albicans by PCR in blood of neutropenic mice with systemic candidiasis. J Clin. Microbiol. 33, 625-628.
  159. Verduyn Lunel, F.M., A Voss, E.J. Kuijper, L.B. Gelinck, P.M. Hoogerbrugge, KL. Liem, B.J. Kullberg, and P.E Verweij. 2004. Detection of the Candida antigen mannan in cerebrospinal fluid specimens from patients suspected of having Candida meningitis. J Clin. Microbiol. 42, 867-870.
  160. Verghese, S.L., P. Padrnaja, P. Sutha, T. Mathew, and ES. John .. 2000. Rapid identification of fluconazole resistance using CHROMagar Candida. Ind. J Pathol. Microbiol. 43, 343-346.
  161. Verweij, P.E., 1.M. Breuker, AJ. Rijs, and J.F. Meis. 1999. Comparative study of seven commercial yeast identification systems. J Clin. Pathol. 52, 271-273.
  162. Vetter, E., e. Torgerson, A Feuker, J. Hughes, S. Harmsen, e. Schleck, e. Horstmeier, G Roberts, and F. Cockerill 3rd. 2001. Comparison of the BACTEC MYCOIF Lytic bottle to the isolator tube, BACTEC Plus Aerobic F/bottle, and BACTEC Anaerobic Lytic/lO bottle and comparison of the BACTEC Plus Aerobic Flbottle to the Isolator tube for recovery of bacteria, mycobacteria, and fungi from blood. J Clin. Microbiol. 39, 4380-4386.
  163. Wadlin, J.K., G. Hanko, R Stewart, J. Pape, and 1. Nachamkin. 1999. Comparison of three commercial systems for identification of yeasts commonly isolated in the clinical microbiology laboratory. J Clin. Microbiol. 37, 1967-1970.
  164. Walsh, T.J. and S.J. Chanock. 1998. Diagnosis of invasive fungal infections: advances in nonculture systems. Curro Clin. Top Infect. Dis. 18, 101-153.
  165. Walsh, T.J., A Francesconi, M. Kasai, and S.J. Chanock. 1995a. PCR and single-strand conformational polymorphism for recognition of medically important opportunistic fungi. J Clin. Microbiol. 33, 3216-3220.
  166. Walsh, T.J., J.W Hathorn, J.D. Sobel, WG. Merz, V. Sanchez, S.M. Maret, H.R Buckley, M.A Pfaller, R Schaufele, and e. Sliva. 1991. Detection of circulating Candida enolase by immunoassay in patients with cancer and invasive candidiasis. N Eng J Med. 324, 1026-1031.
  167. Walsh, T.J., J.W Lee, T Sein, R Schaufele, J. Bacher, A.C. Switchenko, T'C. Goodman, and P.A. Pizzo. 1994. Serum D-arabinitol measured by automated quantitative enzymatic assay for detection and therapeutic monitoring of experimental disseminated candidiasis: correlation with tissue concentrations of Candida albicans. J Med. Vet. Mycol. 32, 205-215.
  168. Walsh, T.J., WG Merz, J.W Lee, R Schaufele, T Sein, P.O. Whitcomb, M. Ruddel, W. Bums, J.R Wingard, and Ae. Switchenko. 1995b. Diagnosis and therapeutic monitoring of invasive candidiasis by rapid enzymatic detection of serum D-arabinitol. Am J Med. 99, 164-172.
  169. Washington, J.A 1994. Collection, transport, and processing of blood cultures. Clin Lab. Med. 14, 59-68.
  170. Wildfeuer, A, R Schlenk, and W Friedrich. 1996. Detection of Candida albicans DNA with a yeast-specific primer system by polymerase chain reaction. Mycoses. 39, 341-346.
  171. Willinger, B. and M. Manafi. 1999. Evaluation of CHROMagar Candida for rapid screening of clinical specimens for Candida species. Mycoses. 4.2, 61-65.
  172. Wingard, J.R 1995. Importance of Candida species other than C. albicans as pathogens in oncology patients. Clin. Infect. Dis. 20, 115-125.
  173. Wong, B., E.M. Bernard, J.W Gold, D. Fong, and D. Armstrong. 1982. The arabinitol appearance rate in laboratory animals and humans: estimation from the arabinitol/creatinine ratio and relevance to the diagnosis of candidiasis. J Infect. Dis. 146, 353359.
  174. Wong, B., KL. Brauer, J.R Clemons, and S. Beggs. 1990. Effects of gastrointestinal candidiasis, antibiotics, dietary arabinitol, and cortisone acetate on levels of the Candida metabolite Darabinitol in rat serum and urine. Infect. Immun. 58, 283-288.
  175. Yeo, S.F., Y. Zhang, D. Schafer, S. Campbell, and B. Wong. 2000. A rapid, automated enzymatic fluorometric assay for determination of D-arabinitol in serum. J Clin. Microbiol. 38, 14391443.
  176. Yera, H., B. Sendid, N. Francois, D. Camus, and D. Poulain. 2001. Contribution of serological tests and blood culture to the early diagnosis of systemic candidiasis. Eur. J Clin. Microbiol. Infect. Dis. 20, 864-870.
  177. Yoshida, M., T Obayashi, A Iwama, M. Ito, S. Tsunoda, T. Suzuki, K Muroi, M. Ohta, S. Sakamoto, and Y. Miura. 1997. Detection of plasma (I ~3)-f3-D-glucan in patients with Fusarium, Trichosporon, Saccharomyces and Acremonium fungaemias. J Med. Vet. Mycol. 35, 371-374.