Skip to main content

Advertisement

SpringerLink
Log in

Echinocandins for Primary Therapy of Candidemia: Time for a Paradigm Shift?

  • Current Management of Fungal Infections (L Ostrosky-Zeichner, Section Editor)
  • Published:
Current Fungal Infection Reports Aims and scope Submit manuscript

Abstract

Candidemia is a common healthcare-associated bloodstream infection that is continuing to increase in incidence. Candidemia is associated with significant morbidity and mortality, which may be potentiated by delays in the initiation of early and appropriate therapy. Recently, the epidemiology of candidemia has shifted, and infections due to non-albicans Candida species as the causative pathogens have increased in frequency. Several studies have been published over the past 5 years in relation to the management of candidemia. Echinocandins have demonstrated favorable clinical responses with a low incidence of adverse effects in patients with candidemia due to both Candida albicans and non-albicans Candida species and, as such, have emerged as the preferred initial therapy.

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

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Wisplinghoff H, Bischoff T, Tallent SM, et al. 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 

  2. Eggimann P, Garbino J, Pittet D. Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis. 2003;3(11):685–702.

    Article  PubMed  Google Scholar 

  3. Hidron AL, Edwards JR, Patel J, et al. NHSN annual update: antimicrobial resistant pathogens associated with epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Infect Control Hosp Epidemiol. 2008;29(11):996–1011.

    Article  PubMed  Google Scholar 

  4. Vincent JL, Rello J, Marshall J, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323–9.

    Article  CAS  PubMed  Google Scholar 

  5. Magill SS, Edwards JR, Bamberg W, et al. Multistate point prevalence survey of health care associated infections. N Engl J Med. 2014;370(13):1198–208. Reported that candidemia was the leading cause of primary health care associated blood stream infection among surveyed hospitals.

    Article  CAS  PubMed  Google Scholar 

  6. Horn DL, Neofytos D, Anaissie EJ, et al. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin Infect Dis. 2009;48(12):1695–703.

    Article  CAS  PubMed  Google Scholar 

  7. Pfaller MA, Diekema DJ. Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standards Institute broth microdilution methods, 2010 to 2012. J Clin Microbiol. 2012;50:2846–56.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Diekema D, Arbefeville S, Boyken L, Kroeger J, Pfaller M. The changing epidemiology of healthcare-associated candidemia over three decades. Diagn Microbiol Infect Dis. 2012;73(1):45–8.

    Article  PubMed  Google Scholar 

  9. Pfaller MA, Andes DR, Diekema DJ, et al. Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2496 patients: data from the prospective antifungal therapy (PATH) registry 2004–2008. PLoS One. 2014;9(7):e101510.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Maubon D, Garnaud C, Calandra T, et al. Resistance of Candida spp. to antifungal drugs in the ICU: where are we now? Intensive Care Med. 2014;40(9):1241–55.

    Article  CAS  PubMed  Google Scholar 

  11. Dimopoulos G, Antonopoulou A, Armaganidis A, Vicent JL. How to select an antifungal agent in critically ill patients. J Crit Care. 2013;28:717–27.

    Article  PubMed  Google Scholar 

  12. Rex JH, Bennett JE, Sugar AM, et al. A randomized trial comparing fluconazole with amphotericin b for the treatment of candidemia in patients without neutropenia. Candidemia study group and the national institute. N Engl J Med. 1994;331:1325–30.

    Article  CAS  PubMed  Google Scholar 

  13. Eschenauer GA, Carver PL, Lin SW, et al. Fluconazole versus an echinocandin for C. glabrata fungaemia: a retrospective cohort study. J Antimicrob Chemother. 2013;68:922–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Neoh CF, Slavin M, Chen SC, et al. Echinocandins in the treatment of candidaemia and invasive candidiasis: clinical and economic perspectives. Int J Antimicrob Agents. 2014;43:207–14.

    Article  CAS  PubMed  Google Scholar 

  15. Pfaller MA, Castanheira M, Lockhart SR, et al. Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata. J Clin Micro. 2012;50(4):1199–203.

    Article  CAS  Google Scholar 

  16. Wisplinghoff H, Ebbers J, Geurtz L, et al. Nosocomial bloodstream infections due to Candida spp. in the USA: species distribution, clinical features and antifungal susceptibilities. Int J Antimicrob Agents. 2014;43(1):78–81.

    Article  CAS  PubMed  Google Scholar 

  17. Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the infectious diseases society of America. Clin Infect Dis. 2009;48:503–35.

    Article  CAS  PubMed  Google Scholar 

  18. Chen SC, Slavin MA, Sorrell TC. Echinocandin antifungal drugs in fungal infections: a comparison. Drugs. 2011;71(1):11–41.

    Article  PubMed  Google Scholar 

  19. Alexander BD, Johnson MD, Pfeiffer CD, et al. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis. 2013;56(12):1424–732.

    Article  Google Scholar 

  20. Ferreira JA, Carr JH, Starling CE, de Resende MA, Donlan RM. Biofilm formation and effect of caspofungin on biofilm structure of Candida species bloodstream isolates. Antimicrob Agents Chemother. 2009;53(10):4377–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Pappas PG, Rotstein CM, Betts RF, et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis. 2007;45:883–93.

    Article  CAS  PubMed  Google Scholar 

  22. Mora-Duarte J, Betts R, Rotstein C, et al. Comparison of caspofungin and amphotericin b for invasive candidiasis. N Engl J Med. 2002;347:2020–9.

    Article  CAS  PubMed  Google Scholar 

  23. Kuse ER, Chetchotisakd P, da Cunha CA, et al. Micafungin versus liposomal amphotericin b for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet. 2007;369:1519–27.

    Article  CAS  PubMed  Google Scholar 

  24. Reboli AC, Rotstein C, Pappas PG, Chapman SW, Kett DH, Kumar D, et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. 2007;356:2472–82.

    Article  CAS  PubMed  Google Scholar 

  25. Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect. 2012;18(Suppl):19–37. Recent guidelines crafted by the European Fungal Infection Study Group that identified echinocandins as the preferred initial therapy for candidemia and invasive candidiasis.

    Article  CAS  PubMed  Google Scholar 

  26. Shields RK, Nguyen MH, Press EG, et al. Anidulafungin and micafungin MIC breakpoints are superior to that of caspofungin for identifying FKS mutant Candida glabrata strains and echinocandin resistance. Antimicrob Agents Chemother. 2013;57(12):6361–15.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Andes DR, Safdar N, Baddley JW, 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. Important study evaluating the impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis. Two factors were associated with improved survival: treatment with an echinocandin and removal of a central venous catheter during treatment.

    Article  CAS  PubMed  Google Scholar 

  28. Beyda ND, Lewis RE, Garey KW. Echinocandin resistance in Candida species, mechanisms of reduced susceptibility and therapeutic approaches. Ann Pharmacother. 2012;46(7–8):1086–96.

    Article  PubMed  Google Scholar 

  29. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts; third informational supplement. Document M27-S3. Wayne, PA: CLSI; 2008.

  30. Arendrup MC, Sulim S, Holm A, et al. Diagnostic issues, clinical characteristics, and outcomes for patients with fungemia. J Clin Microbiol. 2011;49:3300–8.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Pfaller MA, Moet GJ, Messer SA, Jones RN, Castanheira M. Candida bloodstream infections: comparison of species distributions and antifungal resistance patterns in community onset and nosocomial isolates in the SENTRY Antimicrobial Surveillance Program, 2008–2009. Antimicrob Agents Chemother. 2011;55:561–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Eschenauer GA, Nguyen MH, Shoham S, Vazquez JA, et al. Real-world experience with echinocandin MICs against Candida species in a multicenter study of hospitals that routinely perform susceptibility testing of bloodstream isolates. Antimicrob Agents Chemother. 2014;58(4):1897–906.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Espinel-Ingroff A, Arendrup MC, Pfaller MA, et al. Interlaboratory variability of caspofungin MICs for Candida spp. using CLSI and EUCAST methods, should the clinical laboratory be testing this agent? Antimicrob Agents Chemother. 2013;57(12):5836–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Bow EJ, Evans G, Fuller J, et al. Canadian clinical practice guidelines for invasive candidiasis in adults. Can J Infect Dis Med Microbiol. 2010;21(4):e122–50.

    PubMed Central  PubMed  Google Scholar 

  35. Colombo AL, Guimaraes T, Camargo LF, Richtmann R, de Queiroz-Telles F, Salles MJ, et al. Brazilian guidelines for the management of candidiasis—a joint meeting report of three medical societies: sociedade brasileira de infectologia, sociedade paulista de infectologia and sociedade brasileira de medicina tropical. Braz J Infect Dis. 2013;17:283–312.

    Article  PubMed  Google Scholar 

  36. Ruhnke M, Rickerts V, Cornely OA, et al. Diagnosis and therapy of Candida infections: joint recommendations of the German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy. Mycoses. 2011;54:279–310.

    Article  CAS  PubMed  Google Scholar 

  37. Deshpande A, Gaur S, Bal AM. Candidaemia in the non-neutropenic patient: a critique of the guidelines. Int J Antimicrob Agents. 2013;42(4):294–300.

    Article  CAS  PubMed  Google Scholar 

  38. Glockner A, Cornely OA. Practical considerations on current guidelines for the management of non-neutropenic adult patients with candidaemia. Mycoses. 2013;56(1):11–20.

    Article  CAS  PubMed  Google Scholar 

  39. Kett DH, Shorr AF, Reboli AC, Reisman AL, Biswas P, Schlamm HT. Anidulafungin compared with fluconazole in severely ill patients with candidemia and other forms of invasive candidiasis: support for the 2009 IDSA treatment guidelines for candidiasis. Crit Care. 2011;15:R253. Subgroup analysis of clinical trial comparing anidulafungin with fluconazole for treatment of candidemia and invasive candidiasis; anidulafungin was associated with significantly better global response rate. Study findings supported the 2009 IDSA guidelines recommending an echinocandin as initial therapy for candidemia in patients with moderately severe to severe illness.

    Article  PubMed Central  PubMed  Google Scholar 

  40. Colombo AL, Guimaraes T, Sukienik T, et al. Prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period. Intensive Care Med. 2014;40(10):1489–98. Retrospective study of adult ICU patients in Brazil that showed improved survival among patients with candidemia who were treated with an echinocandin on multivariate analysis.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Reboli AC, Shorr AF, Rotstein C, Pappas PG, Kett DH, Schlamm HT, et al. Anidulafungin compared with fluconazole for treatment of candidemia and other forms of invasive candidiasis caused by Candida albicans: a multivariate analysis of factors associated with improved outcome. BMC Infect Dis. 2011;11:261. Post hoc analysis of patients with C. albicans candidemia or invasive candidiasis to determine factors impacting global response to treatment. Receipt of anidulafungin was associated with improved global response.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Eschenauer GA, Carver PL, Lin SW, et al. Fluconazole versus an echinocandin for Candida glabrata fungaemia: a retrospective cohort study. J Antimicrob Chemother. 2013;68:922–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

ᅟ

Conflict of Interest

RE Colombo declares no conflicts of interest.

J Vazquez has received consulting fees from T2 Biosystems, Forest, Cidara, and Astellas; research grants from Merck and Astellas; and speaker honoraria from Astellas and Forest. Fees for participating in review activities such as data monitoring boards, statistical analysis, end point committees are from Pfizer and Astellas.

Human and Animal Rights and Informed Consent

All studies by the authors involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.

Author information

Authors and Affiliations

  1. Department of Medicine, Section of Infectious Diseases, Georgia Regents University, 1120 15th Street, AE-3024, Augusta, GA, 30912, USA

    Rhonda E. Colombo & Jose Vazquez

Authors
  1. Rhonda E. Colombo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jose Vazquez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jose Vazquez.

Additional information

This article is part of the Topical Collection on Current Management of Fungal Infections

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Colombo, R.E., Vazquez, J. Echinocandins for Primary Therapy of Candidemia: Time for a Paradigm Shift?. Curr Fungal Infect Rep 9, 15–22 (2015). https://doi.org/10.1007/s12281-014-0215-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12281-014-0215-9

Keywords

Search

Navigation