Skip to main content

Advertisement

SpringerLink
Log in

Persistent Candidemia in adults: underlying causes and clinical significance in the antifungal stewardship era

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

To investigate the causes and the clinical significance of persistent candidemia (PC) in adults diagnosed in a tertiary hospital with an active antifungal stewardship program. Retrospective cohort including all adults with candidemia from 2010 to 2018. PC was defined as any positive follow-up blood culture (BC) obtained ≥ 5 days from the first BCs yielding the same Candida species. PC was detected in 35/255 (13.7%) patients. There were no differences regarding antifungal adequacy in PC vs. non-PC (94.3% vs. 82.3%, p = 0.084) and primary source control (63.3% vs. 76.4%, p = 0.172) at the time of the follow-up BCs. The average time until source control (2 [0–37] vs. 2 days [0–44], p = 0.311) or adequate antifungal treatment (2 [0–26] vs. 2 days [− 2–10], p = 0.748) was similar. Patients with PC had more non-ocular complications (31.4% vs. 10.5%, p = 0.002). No impact on 30-day mortality was observed (31.4% vs. 22.3%, p = 0.238). The only independent factor associated with PC was to have a previously undetected site of infection [OR 4.28, 95%CI (1.77–10.34), p = 0.001]. Persistent candidemia was not associated with inadequate or delayed therapeutic management, nor higher 30-day mortality rates. Timely screening and control of unexpected infection sources are encouraged to shorten hospitalization and improve patient care.

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

Similar content being viewed by others

References

  1. Noyola DE, Fernandez M, Moylett EH, Baker CJ (2001) Ophthalmologic, visceral, and cardiac involvement in neonates with candidemia. Clin Infect Dis 32(7):1018–1023

    Article  CAS  PubMed  Google Scholar 

  2. Fraser VJ, Jones M, Dunkel J, Storfer S, Medoff G, Dunagan WC (1992) Candidemia in a tertiary care hospital: epidemiology, risk factors, and predictors of mortality. Clin Infect Dis 15(3):414–421

    Article  CAS  PubMed  Google Scholar 

  3. Luzzati R, Amalfitano G, Lazzarini L et al (2000) Nosocomial candidemia in non-neutropenic patients at an Italian tertiary care hospital. Eur J Clin Microbiol Infect Dis 19(8):602–607

    Article  CAS  PubMed  Google Scholar 

  4. Zaoutis TE, Greves HM, Lautenbach E, Bilker WB, Coffin SE (2004) Risk factors for disseminated candidiasis in children with candidemia. Pediatr Infect Dis J 23(7):635–641

    Article  PubMed  Google Scholar 

  5. Nucci M (2011) Persistent candidemia: causes and investigations. Curr Fungal Infect Rep 5(1):3–11

    Article  Google Scholar 

  6. Kang SJ, Kim SE, Kim UJ et al (2017) Clinical characteristics and risk factors for mortality in adult patients with persistent candidemia. J Infect Elsevier 75(3):246–253

    Article  Google Scholar 

  7. Vena A, Munoz P, Corisco R, et al. Efficacy of a “check-list” intervention bundle on the clinical evolution of patients with Candida bloodstream infections. 27th ECCMID. 2017. p. 24–25

  8. Valerio M, Muñoz P, Rodríguez CG et al (2015) Antifungal stewardship in a tertiary-care institution: a bedside intervention. Clin Microbiol Infect 21(5):492.e1–492.e9

    Article  CAS  Google Scholar 

  9. Muñoz P, Valerio M, Vena A, Bouza E (2015) Antifungal stewardship in daily practice and health economic implications. Mycoses 58:14–25

    Article  PubMed  Google Scholar 

  10. Vena A, Bouza E, Valerio M et al (2017) Candidemia in non-ICU surgical wards: comparison with medical wards. PLoS One Public Libr Sci 12(10):e0185339

    Article  CAS  Google Scholar 

  11. Mermel LA, Allon M, Bouza E et al (2009) Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 49(1):1–45

    Article  CAS  PubMed  Google Scholar 

  12. Pappas PG, Kauffman CA, Andes DR et al (2016) Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis Oxford Univ Press 62(4):e1–e50

  13. Arendrup MC, Cuenca-Estrella M, Lass-Flörl C, Hope W (2012) EUCAST-AFST. EUCAST technical note on the EUCAST definitive document EDef 7.2: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts EDef 7.2 (EUCAST-AFST)*. Clin Microbiol Infect 18(7):E246–E247

    Article  CAS  PubMed  Google Scholar 

  14. Marcos-Zambrano LJ, Escribano P, Bouza E, Guinea J (2014) Production of biofilm by Candida and non-Candida spp. isolates causing fungemia: comparison of biomass production and metabolic activity and development of cut-off points. Int J Med Microbiol 304(8):1192–1198

    Article  CAS  PubMed  Google Scholar 

  15. Marcos-Zambrano LJ, Gómez-Perosanz M, Escribano P, Zaragoza O, Bouza E, Guinea J (2016) Biofilm production and antibiofilm activity of echinocandins and liposomal amphotericin B in echinocandin-resistant yeast species. Antimicrob Agents Chemother 60(6):3579–3586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nucci M, Perfect JR (2008) When primary antifungal therapy fails. Clin Infect Dis 46(9):1426–1433

    Article  PubMed  Google Scholar 

  17. Baden LR, Bensinger W, Angarone M et al (2012) Prevention and treatment of cancer-related infections. J Natl Compr Cancer Netw 10(11):1412–1445

    Article  CAS  Google Scholar 

  18. Ruhnke M, Schwartz S (2016) Recent developments in the management of invasive fungal infections in patients with oncohematological diseases. Ther Adv Hematol SAGE Publ 7(6):345–359

    Article  Google Scholar 

  19. Clancy CJ, Nguyen MH (2013) Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis 56(9):1284–1292

    Article  PubMed  Google Scholar 

  20. Li W-S, Chen Y-C, Kuo S-F, Chen F-J, Lee C-H (2018) The impact of biofilm formation on the persistence of candidemia. Front Microbiol 9:1196

    Article  PubMed  PubMed Central  Google Scholar 

  21. Monfredini PM, Souza ACR, Cavalheiro RP, Siqueira RA, Colombo AL (2017) Clinical impact of Candida spp. biofilm production in a cohort of patients with candidemia. Med Mycol 56(7):803–808

    Article  CAS  Google Scholar 

  22. Lin K-Y, Chen P-Y, Chuang Y-C et al (2018) Effectiveness of echinocandins versus fluconazole for treatment of persistent candidemia: a time-dependent analysis. J Inf Secur 77(3):242–248

    Google Scholar 

  23. Muñoz P, Agnelli C, Guinea J et al (2018) Is biofilm production a prognostic marker in adults with candidaemia? Clin Microbiol Infect 24(9):1010–1015

    Article  PubMed  Google Scholar 

  24. Hamdy RF, Zaoutis TE, Seo SK (2017) Antifungal stewardship considerations for adults and pediatrics. Virulence 8(6):658–672

    Article  PubMed  Google Scholar 

  25. Nucci M, Anaissie E, Betts RFF et al (2010) Early removal of central venous catheter in patients with candidemia does not improve outcome: analysis of 842 patients from 2 randomized clinical trials. Clin Infect Dis 51(3):295–303

    Article  PubMed  Google Scholar 

  26. Garnacho-Montero J, Diaz-Martin A, Garcia-Cabrera E, Ruiz Perez de Pipaon M, Hernandez-Caballero C, Lepe-Jimenez JA (2013) Impact on hospital mortality of catheter removal and adequate antifungal therapy in Candida spp. bloodstream infections. J Antimicrob Chemother 68(1):206–213

    Article  CAS  PubMed  Google Scholar 

  27. Caccese R, Carfagna P, Pistilli N, Massetti AP, Falcone M, Venditti M (2012) Candidal thrombophlebitis of central veins: case report and review. Med Mycol 50(3):299–304

    Article  PubMed  Google Scholar 

  28. Mahmood M, Kendi AT, Ajmal S, et al (2017) Meta-analysis of 18F-FDG PET/CT in the diagnosis of infective endocarditis. J Nucl Cardiol. Advance online publication. https://doi.org/10.1007/s12350-017-1092-8

  29. Sharma P, Mukherjee A, Karunanithi S, Bal C, Kumar R (2014) Potential role of 18 F-FDG PET/CT in patients with fungal infections. Am J Roentgenol American Roentgen Ray Society 203(1):180–189

    Article  Google Scholar 

  30. Kauffman C (2015) Complications of candidemia in ICU patients: endophthalmitis, osteomyelitis, endocarditis. Semin Respir Crit Care Med. Thieme Medical Publishers 36(05):641–649

    Article  PubMed  Google Scholar 

  31. Fernández-Cruz A, Cruz Menárguez M, Muñoz P et al (2015) The search for endocarditis in patients with candidemia: a systematic recommendation for echocardiography? A prospective cohort. Eur J Clin Microbiol Infect Dis 34(8):1543–1549

    Article  PubMed  Google Scholar 

  32. Safdar A, Bannister TW, Safdar Z (2004) The predictors of outcome in immunocompetent patients with hematogenous candidasis. Int J Infect Dis 8(3):180–186

    Article  PubMed  Google Scholar 

  33. Velasco E, Bigni R (2008) A prospective cohort study evaluating the prognostic impact of clinical characteristics and comorbid conditions of hospitalized adult and pediatric cancer patients with candidemia. Eur J Clin Microbiol Infect Dis 27(11):1071–1078

    Article  CAS  PubMed  Google Scholar 

  34. Phillips P, Shafran S, Garber G et al (1997) Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group. Eur J Clin Microbiol Infect Dis 16(5):337–345

    Article  CAS  PubMed  Google Scholar 

  35. Chen C-Y, Huang S-Y, Tsay W et al (2012) Clinical characteristics of candidaemia in adults with haematological malignancy, and antimicrobial susceptibilities of the isolates at a medical centre in Taiwan, 2001–2010. Int J Antimicrob Agents 40(6):533–538

    Article  CAS  PubMed  Google Scholar 

  36. Bassetti M, Righi E, Montravers P, Cornely OA (2018) What has changed in the treatment of invasive candidiasis? A look at the past 10 years and ahead. J Antimicrob Chemother 73(suppl_1):i14–i25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Puig-Asensio M, Padilla B, Garnacho-Montero J et al (2014) Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect 20(4):O245–O254

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank all participants of the COMIC Study Group (Collaborative Group on Mycoses): F. Anaya, R. Bañares, E. Bouza, A. Bustinza, E. Chamorro, P. Escribano, A.Fernández-Cruz, J. Fernández-Quero, I. Frias, J. Gayoso, P. Gijón, J. Guinea, J. Hortal, M. C. Martínez, I. Márquez, M. C. Menárguez, P. Muñoz, M. Navarro, B. Padilla, J. Palomo, T. Peláez, J. Peral, B. Pinilla, D. Rincón, C. G. Rodríguez, M. Rodríguez, M Salcedo, M.Sánchez-Somolinos, M. Sanjurjo, M. Valerio, E. Verde, and E. Zamora.

Funding

This study was supported by Fondo de Investigación Sanitaria (FIS) - PM (PI13/01148) and LJMZ (PI14/00740); CA was supported by CAPES Foundation, Brazil/PDSE (88881.187981/2018-01); PE (CPI15/00115) and JG (CPII15/00006) are recipients of a Miguel Servet grant, and AV (CM15/00181) was supported by a Rio Hortega grant from Instituto de Salud Carlos III (ISCIII), also co-financed by the European Regional Development Fund (FEDER) “A way of making Europe.” Additional funding was received through the Plan Nacional de I+D+I 2013-2016, and PROgrama MULtidisciplinar para la Gestión de Antifúngicos y la Reducción de Candidiasis Invasora (PROMULGA) II Project.

Author information

Authors and Affiliations

  1. Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Calle Doctor Esquerdo 46, 28007, Madrid, Spain

    Caroline Agnelli, Maricela Valerio, Emilio Bouza, Antonio Vena, Jesús Guinea, María del Carmen Martínez-Jiménez, Laura Judith Marcos-Zambrano, Pilar Escribano & Patricia Muñoz

  2. Gregorio Marañón Sanitary Research Institute, Madrid, Spain

    Caroline Agnelli, Maricela Valerio, Emilio Bouza, Antonio Vena, Jesús Guinea, María del Carmen Martínez-Jiménez, Laura Judith Marcos-Zambrano, Pilar Escribano & Patricia Muñoz

  3. Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

    Caroline Agnelli

  4. CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Madrid, Spain

    Emilio Bouza, Jesús Guinea & Patricia Muñoz

  5. Department of Medicine, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain

    Emilio Bouza, Antonio Vena, Jesús Guinea, Laura Judith Marcos-Zambrano, Pilar Escribano & Patricia Muñoz

  6. Computational Biology Group, Precision Nutrition and Cancer Research Program, IMDEA Food Institute, Madrid, Spain

    Laura Judith Marcos-Zambrano

Authors
  1. Caroline Agnelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maricela Valerio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emilio Bouza
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antonio Vena
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jesús Guinea
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. María del Carmen Martínez-Jiménez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Laura Judith Marcos-Zambrano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pilar Escribano
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Patricia Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the COMIC Study Group (Collaborative Group on Mycosis)

Corresponding author

Correspondence to Caroline Agnelli.

Ethics declarations

This study was approved by the institutional ethics committee (Comité Ético de Investigación Clínica del Hospital Gregorio Marañón [CEIC-A1], study code MICRO.HGUGM.2015–071). The need for an informed consent was waived owing to the non-interventional, retrospective design of the study.

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Agnelli, C., Valerio, M., Bouza, E. et al. Persistent Candidemia in adults: underlying causes and clinical significance in the antifungal stewardship era. Eur J Clin Microbiol Infect Dis 38, 607–614 (2019). https://doi.org/10.1007/s10096-019-03477-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-019-03477-3

Keywords

Search

Navigation