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Invasive candidiasis: from mycobiome to infection, therapy, and prevention

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Abstract

Candida spp. are commonly found in humans, colonizing most healthy individuals. A high prevalence of invasive candidiasis has been reported in recent years. Here, we assess the relation between Candida spp. as part of the human mycobiome, the host defense mechanisms, and the pathophysiology of invasive disease in critically ill patients. Many hypotheses have been proposed to explain the different immune responses to the process where Candida goes through healthy mycobiome to colonization to invasion; the involvement of other microbiota inhabitants, changes in temperature, low nitrogen levels, and the caspase system activation have been described. Patients admitted to an intensive care unit (ICU) are at the highest risk for invasive candidiasis, mostly due to the severity of their disease, immune-suppressive states, prolonged length of stay, broad-spectrum antibiotics, septic shock, and Candida colonization. The first approach should be using predictive scores as screening, followed by the determination of biomarkers (when available), and, in the near future, probably immune-genomics and analysis of the clinical background in order to initiate prompt and correct treatment. Regarding treatment, the initiation with an echinocandin is strongly recommended in critically ill patients. In conclusion, prompt treatment and adequate source control in the more severe patients remains the ultimate goal, as well as restoration of a healthy microbiota.

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References

  1. Human Microbiome Project Consortium (2012) Structure, function and diversity of the healthy human microbiome. Nature 486:207–214

    Article  Google Scholar 

  2. Cui L, Morris A, Ghedin E (2013) The human mycobiome in health and disease. Genome Med 5:63

    Article  PubMed  PubMed Central  Google Scholar 

  3. Oever JT, Netea MG (2014) The bacteriome–mycobiome interaction and antifungal host defense. Eur J Immunol 44(11):3182–3191

    Article  PubMed  Google Scholar 

  4. Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348(16):1546–1554

    Article  PubMed  Google Scholar 

  5. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD et al; EPIC II Group of Investigators (2009) International study of the prevalence and outcomes of infection in intensive care units. JAMA 302:2323–2329

    Article  CAS  PubMed  Google Scholar 

  6. Bassetti M, Righi E, Ansaldi F, Merelli M, Trucchi C, De Pascale G et al (2014) A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med 40(6):839–845

    Article  CAS  PubMed  Google Scholar 

  7. Bassetti M, Righi E, Ansaldi F, Merelli M, Scarparo C, Antonelli M et al (2015) A multicenter multinational study of abdominal candidiasis: epidemiology, outcomes and predictors of mortality. Intensive Care Med 41(9):1601–1610

    Article  PubMed  Google Scholar 

  8. Schuijt TJ, van der Poll T, de Vos WM, Wiersinga WJ (2013) The intestinal microbiota and host immune interactions in the critically ill. Trends Microbiol 21(5):221–229

    Article  CAS  PubMed  Google Scholar 

  9. Oever JT, Netea MG (2014) The bacteriome–mycobiome interaction and antifungal host defense. Eur J Immunol 44:3182–3191

    Article  PubMed  Google Scholar 

  10. Hogan DA, Vik A, Kolter R (2004) A Pseudomonas aeruginosa quorum-sensing molecule influences Candida albicans morphology. Mol Microbiol 54:1212–1223

    Article  CAS  PubMed  Google Scholar 

  11. Shapiro RS, Uppuluri P, Zaas AK, Collins C, Senn H, Perfect JR et al (2009) Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling. Curr Biol 19:621–629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Luo G, Ibrahim AS, Spellberg B, Nobile CJ, Mitchell AP, Fu Y (2010) Candida albicans Hyr1p confers resistance to neutrophil killing and is a potential vaccine target. J Infect Dis 201:1718–1728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kumar S, Bansal A, Chakrabarti A, Singhi S (2013) Evaluation of efficacy of probiotics in prevention of Candida colonization in a PICU—a randomized controlled trial. Crit Care Med 41:565–572

    Article  PubMed  Google Scholar 

  14. Colombo J, Arena A, Codazzi D, Langer M (2014) Intra-abdominal candidiasis and probiotics: we know little but it’s time to try. Intensive Care Med 40(2):297–298

    Article  PubMed  Google Scholar 

  15. Gow NA, van de Veerdonk FL, Brown AJ, Netea MG (2011) Candida albicans morphogenesis and host defence: discriminating invasion from colonization. Nat Rev Microbiol 10(2):112–122

    PubMed  PubMed Central  Google Scholar 

  16. Blumberg HM, Jarvis WR, Soucie JM, Edwards JE, Patterson JE, Pfaller MA et al; National Epidemiology of Mycoses Survey (NEMIS) Study Group (2001) Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. The National Epidemiology of Mycosis Survey. Clin Infect Dis 33:177–186

    Article  CAS  PubMed  Google Scholar 

  17. Eggimann P, Pittet D (2014) Candida colonization index and subsequent infection in critically ill surgical patients: 20 years later. Intensive Care Med 40:1429–1448

    Article  PubMed  PubMed Central  Google Scholar 

  18. Pfaller M, Neofytos D, Diekema D, Azie N, Meier-Kriesche HU, Quan SP et al (2012) Epidemiology and outcomes of candidemia in 3648 patients: data from the Prospective Antifungal Therapy (PATH Alliance®) registry, 2004–2008. Diagn Microbiol Infect Dis 74:323–331

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  20. Montravers P, Dupont H, Eggimann P (2013) Intra-abdominal candidiasis: the guidelines-forgotten non-candidemic invasive candidiasis. Intensive Care Med 39(12):2226–2230

    Article  PubMed  Google Scholar 

  21. Ostrosky-Zeichner L, Sable C, Sobel J, Alexander BD, Donowitz G, Kan V et al (2007) Multicenter retrospective development and validation of a clinical prediction rule for nosocomial invasive candidiasis in the intensive care setting. Eur J Clin Microbiol Infect Dis 26:271–276

    Article  CAS  PubMed  Google Scholar 

  22. Cohen Y, Karoubi P, Adrie C, Gauzit R, Marsepoil T, Zarka D et al (2010) Early prediction of Candida glabrata fungemia in nonneutropenic critically ill patients. Crit Care Med 38:826–830

    Article  PubMed  Google Scholar 

  23. Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr T, Andersen MH et al; Procalcitonin and Survival Study Group (2015) Invasive Candida infections and the harm from antibacterial drugs in critically ill patients: data from a randomized, controlled trial to determine the role of ciprofloxacin, piperacillin–tazobactam, meropenem, and cefuroxime. Crit Care Med 43(3):594–602

    Article  CAS  PubMed  Google Scholar 

  24. Goldstein E, Hoeprich PD (1972) Problems in the diagnosis and treatment of systemic candidiasis. J Infect Dis 125:190–193

    Article  CAS  PubMed  Google Scholar 

  25. 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 56:1284–1292

    Article  PubMed  Google Scholar 

  26. León C, Ruiz-Santana S, Saavedra P, Almirante B, Nolla-Salas J, Alvarez-Lerma F et al; EPCAN Study Group (2006) A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med 34:730–737

    Article  PubMed  Google Scholar 

  27. Paphitou NI, Ostrosky-Zeichner L, Rex JH (2005) Rules for identifying patients at increased risk for candidal infections in the surgical intensive care unit: approach to developing practical criteria for systematic use in antifungal prophylaxis trials. Med Mycol 43:235–243

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  29. Tissot F, Lamoth F, Hauser PM, Orasch C, Flückiger U, Siegemund M et al (2013) β-glucan antigenemia anticipates diagnosis of blood culture-negative intraabdominal candidiasis. Am J Respir Crit Care Med 188(9):1100–1109

    Article  PubMed  Google Scholar 

  30. Posteraro B, De Pascale G, Tumbarello M, Torelli R, Pennisi MA, Bello G et al (2011) Early diagnosis of candidemia in intensive care unit patients with sepsis: a prospective comparison of (1→3)-β-D-glucan assay, Candida score, and colonization index. Crit Care 15:R249

    Article  PubMed  PubMed Central  Google Scholar 

  31. Wójtowicz A, Tissot F, Lamoth F, Orasch C, Eggimann P, Siegemund M et al (2014) Polymorphisms in tumor necrosis factor-α increase susceptibility to intra-abdominal Candida infection in high-risk surgical ICU patients. Crit Care Med 42:e304–e308

    Article  PubMed  Google Scholar 

  32. Oude Lashof AM, Rothova A, Sobel JD, Ruhnke M, Pappas PG, Viscoli C et al (2011) Ocular manifestations of candidemia. Clin Infect Dis 53(3):262–268

    Article  PubMed  Google Scholar 

  33. Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr et al (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48:503–535

    Article  CAS  PubMed  Google Scholar 

  34. Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O et al (2012) ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 18(Suppl 7):19–37

    Article  CAS  PubMed  Google Scholar 

  35. Andes DR, Safdar N, Baddley JW, Playford G, Reboli AC, Rex JH et al (2012) 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 54:1110–1122

    Article  CAS  PubMed  Google Scholar 

  36. Grau S, Luque S, Campillo N, Samsó E, Rodríguez U, García-Bernedo CA et al (2015) Plasma and peritoneal fluid population pharmacokinetics of micafungin in post-surgical patients with severe peritonitis. J Antimicrob Chemother 70(10):2854–2861

    Article  CAS  PubMed  Google Scholar 

  37. Martínez-Jiménez MC, Muñoz P, Valerio M, Vena A, Guinea J, Bouza E (2015) Combination of Candida biomarkers in patients receiving empirical antifungal therapy in a Spanish tertiary hospital: a potential role in reducing the duration of treatment. J Antimicrob Chemother 70(11):3107–3115

    Article  PubMed  Google Scholar 

  38. Eggimann P, Francioli P, Bille J, Schneider R, Wu MM, Chapuis G et al (1999) Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Crit Care Med 27:1066–1072

    Article  CAS  PubMed  Google Scholar 

  39. Pelz RK, Hendrix CW, Swoboda SM, Diener-West M, Merz WG, Hammond J et al (2001) Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients. Ann Surg 233:542–548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Shorr AF, Chung K, Jackson WL, Waterman PE, Kollef MH (2005) Fluconazole prophylaxis in critically ill surgical patients: a meta-analysis. Crit Care Med 33:1928–1935

    Article  CAS  PubMed  Google Scholar 

  41. Ostrosky-Zeichner L, Shoham S, Vazquez J, Reboli A, Betts R, Barron MA et al (2014) MSG-01: a randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting. Clin Infect Dis 58:1219–1226

    Article  CAS  PubMed  Google Scholar 

  42. Muldoon EG, Denning DW (2014) Prophylactic echinocandin: is there a subgroup of intensive care unit patients who benefit? Clin Infect Dis 58:1227–1229

    Article  PubMed  Google Scholar 

  43. Wang JF, Xue Y, Zhu XB, Fan H (2015) Efficacy and safety of echinocandins versus triazoles for the prophylaxis and treatment of fungal infections: a meta-analysis of RCTs. Eur J Clin Microbiol Infect Dis 34(4):651–659

    Article  PubMed  Google Scholar 

  44. Azoulay E, Dupont H, Tabah A, Lortholary O, Stahl JP, Francais A et al (2012) Systemic antifungal therapy in critically ill patients without invasive fungal infection*. Crit Care Med 40:813–822

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Critical Care Department, Vall d’Hebron University Hospital, Ps Vall d’Hebron 119–129, 08035, Barcelona, Spain

    L. Lagunes

  2. Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain

    J. Rello

  3. CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III (CIBERES), Madrid, Spain

    J. Rello

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  1. L. Lagunes
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Correspondence to L. Lagunes.

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Lagunes, L., Rello, J. Invasive candidiasis: from mycobiome to infection, therapy, and prevention. Eur J Clin Microbiol Infect Dis 35, 1221–1226 (2016). https://doi.org/10.1007/s10096-016-2658-0

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  • DOI: https://doi.org/10.1007/s10096-016-2658-0

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