Skip to main content

Advertisement

Log in

Serological biomarkers of candidemia: a retrospective evaluation of three assays

  • Original Paper
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Purpose

Serologic testing allows for rapid detection of candidemia. More data are needed for the Virion\Serion ELISA antigen test (Ag), Hemkit Candida IHA antibody test (Ab), and Wako β-1,3-d-glucan assay (BDG).

Methods

Tests were performed on serum samples from 120 cases of culture-confirmed candidemia and 44 Candida-negative controls. Sensitivities and specificities of individual tests as well as combinations were assessed.

Results

The overall sensitivity of Ag, Ab, and Ag/Ab testing was 30, 40, and 54%, respectively, while in transplant patients it significantly dropped to 16, 26, and 40% (p = 0.02). For BDG testing it was 67%, both overall and in transplant patients. Especially Ag testing performed poorly among women ≤ 65 years with a significantly reduced sensitivity of 9% (p < 0.002). While the sensitivity of Ag/Ab testing was somewhat higher at 67% for C. albicans, it was significantly lower for non-albicans species at 42% (p = 0.006). The sensitivity of BDG testing for C. albicans and non-albicans species was not significantly different at 64 and 69%, respectively. Both Ag/Ab and BDG testing had a high specificity of 93%, for Ag testing it was 100%. Similar sensitivities were calculated for sera sampled on the day of and 4–6 days before sampling of positive blood cultures.

Conclusions

Serological markers are valuable tools for the early diagnosis of candidemia. Ab, Ag, and BDG testing are all characterized by high specificity. The Wako BDG test is significantly more sensitive compared to combined Candida-Ag/Ab testing, particularly in the setting of non-albicans species and specific host factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bassetti M, Merelli M, Righi E, Diaz-Martin A, Rosello EM, Luzzati R, et al. Epidemiology, species distribution, antifungal susceptibility, and outcome of candidemia across five sites in Italy and Spain. J Clin Microbiol. 2013;51:4167–72.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007;20:133–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004;39:309–17.

    Article  PubMed  Google Scholar 

  4. Bassetti M, Righi E, Ansaldi F, Merelli M, Trucchi C, Cecilia T, et al. A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med. 2014;40:839–45.

    Article  CAS  PubMed  Google Scholar 

  5. Weiss E, Timsit J-F. Management of invasive candidiasis in nonneutropenic ICU patients. Ther Adv Infect Dis. 2014;2:105–15.

    PubMed  PubMed Central  Google Scholar 

  6. Kollef M, Micek S, Hampton N, Doherty JA, Kumar A. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis. 2012;54:1739–46.

    Article  CAS  PubMed  Google Scholar 

  7. Cuenca-Estrella M, Verweij PE, Arendrup MC, Arikan-Akdagli S, Bille J, Donnelly JP, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clin Microbiol Infect. 2012;18:9–18.

    Article  CAS  PubMed  Google Scholar 

  8. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1–50.

    Article  PubMed  Google Scholar 

  9. Clancy CJ, Nguyen MH. Diagnosing invasive candidiasis. J Clin Microbiol. 2018;56:01909.

    Article  Google Scholar 

  10. Sendid B, Tabouret M, Poirot JL, Mathieu D, Fruit J, Poulain D. 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. 1999;37:1510–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Tran T, Beal SG. Application of the 1,3-β-d-glucan (Fungitell) assay in the diagnosis of invasive fungal infections. Arch Pathol Lab Med. 2016;140:181–5.

    Article  CAS  PubMed  Google Scholar 

  12. Debusmann F, Schaffrinski M, Rüchel R. Serologische candidose-diagnostik: vergleich von drei antigentests. Der Mikrobiologe. 2008;18:261–2.

    Google Scholar 

  13. Lunel FMV, Mennink-Kersten MASH, Ruegebrink D, van der Lee HAL, Donnelly JP, Blijlevens NMA, et al. Value of Candida serum markers in patients with invasive candidiasis after myeloablative chemotherapy. Diagn Microbiol Infect Dis. 2009;64:408–15.

    Article  CAS  PubMed  Google Scholar 

  14. Friedrich R, Rappold E, Bogdan C, Held J. Comparative analysis of the wako β-glucan test and the fungitell® assay for the diagnosis of candidemia and pneumocystis jirovecii pneumonia. J Clin Microbiol. 2018. https://doi.org/10.1128/JCM.00464-18.

    Article  PubMed  PubMed Central  Google Scholar 

  15. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21.

    Article  PubMed  Google Scholar 

  16. Arendrup MC, Bruun B, Christensen JJ, Fuursted K, Johansen HK, Kjaeldgaard P, et al. National surveillance of fungemia in Denmark (2004 to 2009). J Clin Microbiol. 2011;49:325–34.

    Article  PubMed  Google Scholar 

  17. Mikulska M, Calandra T, Sanguinetti M, Poulain D, Viscoli C. Third European Conference on Infections in Leukemia Group. The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia. Crit Care. 2010;14:R222.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Sendid B, Poirot JL, Tabouret M, Bonnin A, Caillot D, Camus D, et al. Combined detection of mannanaemia and antimannan antibodies as a strategy for the diagnosis of systemic infection caused by pathogenic Candida species. J Med Microbiol. 2002;51:433–42.

    Article  CAS  PubMed  Google Scholar 

  19. Yera H, Sendid B, Francois N, Camus D, Poulain D. Contribution of serological tests and blood culture to the early diagnosis of systemic candidiasis. Eur J Clin Microbiol Infect Dis. 2001;20:864–70.

    Article  CAS  PubMed  Google Scholar 

  20. Held J, Kohlberger I, Rappold E, Busse Grawitz A, Häcker G. Comparison of (1->3)-β-d-glucan, mannan/anti-mannan antibodies, and Cand-Tec Candida antigen as serum biomarkers for candidemia. J Clin Microbiol. 2013;51:1158–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Silva S, Negri M, Henriques M, Oliveira R, Williams DW, Azeredo J. Candida glabrata, Candida parapsilosis and Candida tropicalis: biology, epidemiology, pathogenicity and antifungal resistance. FEMS Microbiol Rev. 2012;36:288–305.

    Article  CAS  PubMed  Google Scholar 

  22. Lu Y, Chen Y-Q, Guo Y-L, Qin S-M, Wu C, Wang K. Diagnosis of invasive fungal disease using serum (1→3)-β-D-glucan: a bivariate meta-analysis. Intern Med. 2011;50:2783–91.

    Article  CAS  PubMed  Google Scholar 

  23. Onishi A, Sugiyama D, Kogata Y, Saegusa J, Sugimoto T, Kawano S, et al. Diagnostic accuracy of serum 1,3-β-d-glucan for pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. J Clin Microbiol. 2012;50:7–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Karageorgopoulos DE, Vouloumanou EK, Ntziora F, Michalopoulos A, Rafailidis PI, Falagas ME. β-d-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis. 2011;52:750–70.

    Article  CAS  PubMed  Google Scholar 

  25. Kratzer C, Graninger W, Lassnigg A, Presterl E. Design and use of Candida scores at the intensive care unit. Mycoses. 2011;54:467–74.

    Article  PubMed  Google Scholar 

  26. León C, Ruiz-Santana S, Saavedra P, Almirante B, Nolla-Salas J, Alvarez-Lerma F, et al. A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med. 2006;34:730–7.

    Article  PubMed  Google Scholar 

  27. Ku NS, Han SH, Choi JY, Kim SB, Kim H-W, Jeong SJ, et al. Diagnostic value of the serum galactomannan assay for invasive aspergillosis: it is less useful in non-haematological patients. Scand J Infect Dis. 2012;44:600–4.

    Article  CAS  PubMed  Google Scholar 

  28. Clancy CJ, Nguyen MH. Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013;56:1284–92.

    Article  PubMed  Google Scholar 

  29. Andes DR, Safdar N, Baddley JW, Playford G, Reboli AC, Rex JH, et al. Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials. Clin Infect Dis. 2012;54:1110–22.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by FUJIFILM Wako Chemicals Europe. We thank Hellen Müller for technical support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Johannes Wagener.

Ethics declarations

Conflict of interest

The authors report financial support for consumables and staff to conduct the study and temporary supply of technical equipment from FUJIFILM Wako Chemicals Europe. The funding source was not involved in the study design, in the collection, analysis and interpretation of data or in writing of the report.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dichtl, K., Seybold, U. & Wagener, J. Serological biomarkers of candidemia: a retrospective evaluation of three assays. Infection 47, 217–224 (2019). https://doi.org/10.1007/s15010-018-1224-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-018-1224-3

Keywords

Navigation