Skip to main content

Advertisement

SpringerLink
Log in

Epidemiology, Clinical Characteristics and Risk Factors for Severity of Chronic Disseminated Candidiasis in Jerusalem, Israel

  • Original Article
  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

Chronic disseminated candidiasis (CDC) occurs mostly in patients with acute hematologic malignancy and its clinical manifestations derive from immune reconstitution following neutrophil recovery. The aim of this study was to describe epidemiological and clinical characteristics of CDC and define risk factors for disease severity. Demographic and clinical data were collected from medical files of patients with CDC hospitalized in two tertiary medical centers in Jerusalem between 2005 and 2020. Associations between different variables and disease severity were evaluated, as well as characterization of Candida species. The study included 35 patients. CDC incidence slightly increased during study years and the average number of involved organs and disease duration was 3 ± 1.26 and 178 ± 123 days, respectively. Candida grew in blood in less than third of cases and the most common isolated pathogen was Candida tropicalis (50%). Histopathological or microbiological workup in patients who underwent an organ biopsy demonstrated Candida in about half of the patients. Nine months after starting antifungals, 43% of the patients still didn't have resolution of organ lesions in imaging modalities. Factors associated with protracted and extensive disease were prolonged fever prior to CDC and absence of candidemia. A C- Reactive Protein (CRP) cutoff level of 7.18 mg/dL was found to predict extensive disease. In conclusion, CDC incidence is increasing and the number of involved organs is higher than previously described. Clinical factors such as fever duration prior to CDC and absence of candidemia can predict severe course of disease and assist in treatment decisions and follow-up planning.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. 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(3):309–17. https://doi.org/10.1086/421946.

    Article  PubMed  Google Scholar 

  2. Mazi PB, Olsen MA, Stwalley D, Rauseo AM, Ayres C, Powderly WG, et al. Attributable mortality of candida bloodstream infections in the modern era: a propensity score analysis. Clin Infect Dis. 2022;75(6):1031–6. https://doi.org/10.1093/cid/ciac004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kullberg BJ, Arendrup MC. Invasive Candidiasis. N Engl J Med. 2015;373(15):1445–56. https://doi.org/10.1056/NEJMra1315399.

    Article  CAS  PubMed  Google Scholar 

  4. 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(4):e1-50. https://doi.org/10.1093/cid/civ933.

    Article  PubMed  Google Scholar 

  5. Verma SP, Dubashi B, Narayanan P, Basu D, Dutta TK, Dhanraj KM. A case of pediatric acute lymphoblastic leukemia with invasive Candidiasis: short review. Indian J Hematol Blood Transfus. 2014;30:S101–4. https://doi.org/10.1007/s12288-013-0274-z.

    Article  Google Scholar 

  6. Chen CY, Cheng A, Tien FM, Lee PC, Tien HF, Sheng WH, et al. Chronic disseminated candidiasis manifesting as hepatosplenic abscesses among patients with hematological malignancies. BMC Infect Dis. 2019;19(1):635. https://doi.org/10.1186/s12879-019-4260-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Anttila VJ, Elonen E, Nordling S, Sivonen A, Ruutu T, Ruutu P. Hepatosplenic candidiasis in patients with acute leukemia: incidence and prognostic implications. Clin Infect Dis. 1997;24(3):375–80. https://doi.org/10.1093/clinids/24.3.375.

    Article  CAS  PubMed  Google Scholar 

  8. Rammaert B, Desjardins A, Lortholary O. New insights into hepatosplenic candidosis, a manifestation of chronic disseminated candidosis. Mycoses. 2012;55(3):e74-84. https://doi.org/10.1111/j.1439-0507.2012.02182.x.

    Article  CAS  PubMed  Google Scholar 

  9. Cole GT, Lynn KT, Seshan KR. Evaluation of a murine model of hepatic candidiasis. J Clin Microbiol. 1990;28(8):1828–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zajac-Spychala O, Ukielska B, Jonczyk-Potoczna K, Konatkowska B, Wachowiak J. Chronic disseminated candidiasis complicated by immune reconstitution inflammatory syndrome in child with acute lymphoblastic leukemia. Case Rep Hematol. 2016;2016:5960150. https://doi.org/10.1155/2016/5960150.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 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(12):1813–21. https://doi.org/10.1086/588660.

    Article  PubMed  Google Scholar 

  12. Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, et al. Revision and update of the consensus definitions of invasive fungal disease from the European organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis. 2020;71(6):1367–76. https://doi.org/10.1093/cid/ciz1008.

    Article  PubMed  Google Scholar 

  13. Bassetti M, Righi E, Costa A, Fasce R, Molinari MP, Rosso R, et al. Epidemiological trends in nosocomial candidemia in intensive care. BMC Infect Dis. 2006;6:21. https://doi.org/10.1186/1471-2334-6-21.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Trick WE, Fridkin SK, Edwards JR, Hajjeh RA, Gaynes RP, National Nosocomial Infections Surveillance System Hospital. Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989–1999. Clin Infect Dis. 2002;35(5):627–30. https://doi.org/10.1086/342300.

    Article  CAS  PubMed  Google Scholar 

  15. Cleveland AA, Harrison LH, Farley MM, Hollick R, Stein B, Chiller TM, et al. Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008–2013: results from population-based surveillance. PLoS One. 2015;10(3):e0120452. https://doi.org/10.1371/journal.pone.0120452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Arastehfar A, Gabaldon T, Garcia-Rubio R, Jenks JD, Hoenigl M, Salzer HJF, et al. Drug-resistant fungi an emerging challenge threatening our limited antifungal armamentarium. Antibiotics Basel. 2020. https://doi.org/10.3390/antibiotics9120877.

    Article  PubMed  PubMed Central  Google Scholar 

  17. The European Committee on Antimicrobial Susceptibility Testing (2018) Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 9.0, Valid from 2018–02–12. EUCAST.

  18. Israel S, Amit S, Israel A, Livneh A, Nir-Paz R, Korem M. The epidemiology and susceptibility of Candidemia in Jerusalem. Israel Front Cell Infect Microbiol. 2019;9:352. https://doi.org/10.3389/fcimb.2019.00352.

    Article  CAS  PubMed  Google Scholar 

  19. Bellolio MF, Bellew SD, Sangaralingham LR, Campbell RL, Cabrera D, Jeffery MM, et al. Access to primary care and computed tomography use in the emergency department. BMC Health Serv Res. 2018;18(1):154. https://doi.org/10.1186/s12913-018-2958-4.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Anttila VJ, Lamminen AE, Bondestam S, Korhola O, Farkkila M, Sivonen A, et al. Magnetic resonance imaging is superior to computed tomography and ultrasonography in imaging infectious liver foci in acute leukaemia. Eur J Haematol. 1996;56(1–2):82–7. https://doi.org/10.1111/j.1600-0609.1996.tb00300.x.

    Article  CAS  PubMed  Google Scholar 

  21. Malekzadeh S, Widmer L, Salahshour F, Egger B, Ronot M, Thoeny HC. Typical imaging finding of hepatic infections: a pictorial essay. Abdom Radiol (NY). 2021;46(2):544–61. https://doi.org/10.1007/s00261-020-02642-z.

    Article  PubMed  Google Scholar 

  22. Shankar J, Solis NV, Mounaud S, Szpakowski S, Liu H, Losada L, et al. Using Bayesian modelling to investigate factors governing antibiotic-induced Candida albicans colonization of the GI tract. Sci Rep. 2015;5:8131. https://doi.org/10.1038/srep08131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hansson GC. Role of mucus layers in gut infection and inflammation. Curr Opin Microbiol. 2012;15(1):57–62. https://doi.org/10.1016/j.mib.2011.11.002.

    Article  CAS  PubMed  Google Scholar 

  24. Cole GT, Halawa AA, Anaissie EJ. The role of the gastrointestinal tract in hematogenous candidiasis: from the laboratory to the bedside. Clin Infect Dis. 1996;22(Suppl 2):S73-88. https://doi.org/10.1093/clinids/22.supplement_2.s73.

    Article  PubMed  Google Scholar 

  25. Pagano L, Mele L, Fianchi L, Melillo L, Martino B, Antonio D, et al. (2002) Chronic disseminated candidiasis in patients with hematologic malignancies. Clinical features and outcome of 29 episodes Haematologica 87(5):535–41

  26. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011;52(4):e56-93. https://doi.org/10.1093/cid/cir073.

    Article  PubMed  Google Scholar 

  27. Della Pepa R, Picardi M, Sora F, Stamouli M, Busca A, Candoni A, et al. Successful management of chronic disseminated candidiasis in hematologic patients treated with high-dose liposomal amphotericin B: a retrospective study of the SEIFEM registry. Support Care Cancer. 2016;24(9):3839–45. https://doi.org/10.1007/s00520-016-3208-0.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007;20(1):133–63. https://doi.org/10.1128/CMR.00029-06.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pfaller MA, Diekema DJ, Gibbs DL, Newell VA, Ellis D, Tullio V, et al. Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-year analysis of susceptibilities of Candida Species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. J Clin Microbiol. 2010;48(4):1366–77. doi:https://doi.org/10.1128/JCM.02117-09

  30. Wingard JR, Merz WG, Saral R. Candida tropicalis: a major pathogen in immunocompromised patients. Ann Intern Med. 1979;91(4):539–43. https://doi.org/10.7326/0003-4819-91-4-539.

    Article  CAS  PubMed  Google Scholar 

  31. Walsh TJ, Merz WG. Pathologic features in the human alimentary tract associated with invasiveness of Candida tropicalis. Am J Clin Pathol. 1986;85(4):498–502. https://doi.org/10.1093/ajcp/85.4.498.

    Article  CAS  PubMed  Google Scholar 

  32. Hot A, Maunoury C, Poiree S, Lanternier F, Viard JP, Loulergue P, et al. Diagnostic contribution of positron emission tomography with [18F]fluorodeoxyglucose for invasive fungal infections. Clin Microbiol Infect. 2011;17(3):409–17. https://doi.org/10.1111/j.1469-0691.2010.03301.x.

    Article  CAS  PubMed  Google Scholar 

  33. Douglas AP, Thursky KA, Worth LJ, Drummond E, Hogg A, Hicks RJ, et al. FDG PET/CT imaging in detecting and guiding management of invasive fungal infections: a retrospective comparison to conventional CT imaging. Eur J Nucl Med Mol Imaging. 2019;46(1):166–73. https://doi.org/10.1007/s00259-018-4062-8.

    Article  CAS  PubMed  Google Scholar 

  34. Anttila VJ, Ruutu P, Bondestam S, Jansson SE, Nordling S, Farkkila M, et al. Hepatosplenic yeast infection in patients with acute leukemia: a diagnostic problem. Clin Infect Dis. 1994;18(6):979–81. https://doi.org/10.1093/clinids/18.6.979.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

    Nerel Cohen, Efrat Orenbuch-Harroch, Karen Olshtain-Pops, Tamar Lachish & Maya Korem

  2. Medical Corps, Israel Defense Forces, Ramat-Gan, Israel

    Nerel Cohen

  3. Medical Intensive Care Unit, Hadassah Medical Center, Jerusalem, Israel

    Efrat Orenbuch-Harroch

  4. The Department of Clinical Microbiology and Infectious Diseases, Hadassah Medical Center, P.O. Box 12000, 9112102, Jerusalem, Israel

    Karen Olshtain-Pops & Maya Korem

  5. Infectious Diseases Unit, Shaare Zedek Medical Center, Jerusalem, Israel

    Tamar Lachish

Authors
  1. Nerel Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Efrat Orenbuch-Harroch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karen Olshtain-Pops
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tamar Lachish
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maya Korem
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MK, NC and EO-H contributed to the study conception, methodology, investigation and design. Material preparation, data collection and analysis were performed by NC. Supervision was performed by MK, EO-H and TL. The first draft of the manuscript was written by NC, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Maya Korem.

Ethics declarations

Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Handling Editor: Ferry Hagen

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 18 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cohen, N., Orenbuch-Harroch, E., Olshtain-Pops, K. et al. Epidemiology, Clinical Characteristics and Risk Factors for Severity of Chronic Disseminated Candidiasis in Jerusalem, Israel. Mycopathologia 188, 873–883 (2023). https://doi.org/10.1007/s11046-023-00755-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-023-00755-9

Keywords

Search

Navigation