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Candida colonization index and subsequent infection in critically ill surgical patients: 20 years laterOpen access

Philippe Eggimann| Didier Pittet
My Paper 20 Years Later
Volume 40, Issue 10 / October , 2014

Pages 1429 - 1448

Abstract

Introduction

For decades, clinicians dealing with immunocompromised and critically ill patients have perceived a link between Candida colonization and subsequent infection. However, the pathophysiological progression from colonization to infection was clearly established only through the formal description of the colonization index (CI) in critically ill patients. Unfortunately, the literature reflects intense confusion about the pathophysiology of invasive candidiasis and specific associated risk factors.

Methods

We review the contribution of the CI in the field of Candida infection and its development in the 20 years following its original description in 1994. The development of the CI enabled an improved understanding of the pathogenesis of invasive candidiasis and the use of targeted empirical antifungal therapy in subgroups of patients at increased risk for infection.

Results

The recognition of specific characteristics among underlying conditions, such as neutropenia, solid organ transplantation, and surgical and nonsurgical critical illness, has enabled the description of distinct epidemiological patterns in the development of invasive candidiasis.

Conclusions

Despite its limited bedside practicality and before confirmation of potentially more accurate predictors, such as specific biomarkers, the CI remains an important way to characterize the dynamics of colonization, which increases early in patients who develop invasive candidiasis.

Keywords

References

  1. Eggimann P, Garbino J, Pittet D (2003) Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis 3:685–702
    • View reference on PubMed
    • View reference on publisher's website
  2. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J, Gomersall C, Sakr Y, Reinhart K, EPIC II Group of Investigators (2009) International study of the prevalence and outcomes of infection in intensive care units. JAMA 302:2323–2329
    • View reference on PubMed
    • View reference on publisher's website
  3. Pfaller M, Neofytos D, Diekema D, Azie N, Meier-Kriesche HU, Quan SP, Horn D (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
    • View reference on PubMed
    • View reference on publisher's website
  4. Guery BP, Arendrup MC, Auzinger G, Azoulay E, Borges Sa M, Johnson EM, Muller E, Putensen C, Rotstein C, Sganga G, Venditti M, Zaragoza Crespo R, Kullberg BJ (2009) Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: part I. Epidemiology and diagnosis. Intensive Care Med 35:55–62
  5. Kett DH, Azoulay E, Echeverria PM, Vincent JL, Extended Prevalence of Infection in ICUSGoI (2011) Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med 39:665–670
    • View reference on PubMed
    • View reference on publisher's website
  6. Marchetti O, Bille J, Fluckiger U, Eggimann P, Ruef C, Garbino J, Calandra T, Glauser MP, Tauber MG, Pittet D, Fungal Infection Network of S (2004) Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991–2000. Clin Infect Dis 38:311–320
    • View reference on PubMed
    • View reference on publisher's website
  7. Eggimann P, Bille J, Marchetti O (2011) Diagnosis of invasive candidiasis in the ICU. Ann Intensive Care 1:37
    • View reference on PubMed
    • View reference on publisher's website
  8. Bassetti M, Marchetti M, Chakrabarti A, Colizza S, Garnacho-Montero J, Kett DH, Munoz P, Cristini F, Andoniadou A, Viale P, Rocca GD, Roilides E, Sganga G, Walsh TJ, Tascini C, Tumbarello M, Menichetti F, Righi E, Eckmann C, Viscoli C, Shorr AF, Leroy O, Petrikos G, De Rosa FG (2013) A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts. Intensive Care Med 39:2092–2106
  9. Gudlaugsson O, Gillespie S, Lee K, Berg JV, Hu J, Messer S, Herwaldt L, Pfaller M, Diekema D (2003) Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis 37:1172–1177
    • View reference on PubMed
    • View reference on publisher's website
  10. Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C (2005) The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis 41:1232–1239
    • View reference on PubMed
    • View reference on publisher's website
  11. Prowle JR, Echeverri JE, Ligabo EV, Sherry N, Taori GC, Crozier TM, Hart GK, Korman TM, Mayall BC, Johnson PD, Bellomo R (2011) Acquired bloodstream infection in the intensive care unit: incidence and attributable mortality. Crit Care 15:R100
    • View reference on PubMed
    • View reference on publisher's website
  12. Morrell M, Fraser VJ, Kollef MH (2005) Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 49:3640–3645
    • View reference on PubMed
    • View reference on publisher's website
  13. Garey KW, Rege M, Pai MP, Mingo DE, Suda KJ, Turpin RS, Bearden DT (2006) Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis 43:25–31
    • View reference on PubMed
    • View reference on publisher's website
  14. Azoulay E, Dupont H, Tabah A, Lortholary O, Stahl JP, Francais A, Martin C, Guidet B, Timsit JF (2012) Systemic antifungal therapy in critically ill patients without invasive fungal infection. Crit Care Med 40:813–822
    • View reference on PubMed
    • View reference on publisher's website
  15. Sipsas NV, Lewis RE, Tarrand J, Hachem R, Rolston KV, Raad II, Kontoyiannis DP (2009) Candidemia in patients with hematologic malignancies in the era of new antifungal agents (2001–2007): stable incidence but changing epidemiology of a still frequently lethal infection. Cancer 115:4745–4752
    • View reference on PubMed
    • View reference on publisher's website
  16. Lortholary O, Desnos-Ollivier M, Sitbon K, Fontanet A, Bretagne S, Dromer F, French Mycosis Study G (2011) Recent exposure to caspofungin or fluconazole influences the epidemiology of candidemia: a prospective multicenter study involving 2,441 patients. Antimicrob Agents Chemother 55:532–538
    • View reference on PubMed
    • View reference on publisher's website
  17. Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD, Infectious Diseases Society of A (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48:503–535
    • View reference on PubMed
    • View reference on publisher's website
  18. Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, Meersseman W, Akova M, Arendrup MC, Arikan-Akdagli S, Bille J, Castagnola E, Cuenca-Estrella M, Donnelly JP, Groll AH, Herbrecht R, Hope WW, Jensen HE, Lass-Florl C, Petrikkos G, Richardson MD, Roilides E, Verweij PE, Viscoli C, Ullmann AJ, Group EFIS (2012) ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 18(Suppl 7):19–37
    • View reference on PubMed
    • View reference on publisher's website
  19. Eggimann P, Garbino J, Pittet D (2003) Management of Candida species infections in critically ill patients. Lancet Infect Dis 3:772–785
    • View reference on PubMed
    • View reference on publisher's website
  20. Playford EG, Eggimann P, Calandra T (2008) Antifungals in the ICU. Curr Opin Infect Dis 21:610–619
    • View reference on PubMed
    • View reference on publisher's website
  21. Eggimann P, Ostrosky-Zeichner L (2010) Early antifungal intervention strategies in ICU patients. Curr Opin Crit Care 16:465–469
    • View reference on PubMed
    • View reference on publisher's website
  22. Montravers P, Dupont H, Eggimann P (2013) Intra-abdominal candidiasis: the guidelines-forgotten non-candidemic invasive candidiasis. Intensive Care Med 39:2226–2230
  23. Pittet D, Monod M, Filthuth I, Frenk E, Suter PM, Auckenthaler R (1991) Contour-clamped homogeneous electric field gel electrophoresis as a powerful epidemiologic tool in yeast infections. Am J Med 91:256S–263S
    • View reference on PubMed
    • View reference on publisher's website
  24. Pittet D, Monod M, Suter PM, Frenk E, Auckenthaler R (1994) Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg 220:751–758
    • View reference on PubMed
    • View reference on publisher's website
  25. van de Veerdonk FL, Kullberg BJ, Netea MG (2010) Pathogenesis of invasive candidiasis. Curr Opin Crit Care 16:453–459
    • View reference on PubMed
    • View reference on publisher's website
  26. Magill SS, Swoboda SM, Shields CE, Colantuoni EA, Fothergill AW, Merz WG, Lipsett PA, Hendrix CW (2009) The epidemiology of Candida colonization and invasive candidiasis in a surgical intensive care unit where fluconazole prophylaxis is utilized: follow-up to a randomized clinical trial. Ann Surg 249:657–665
    • View reference on PubMed
    • View reference on publisher's website
  27. Khan ZU, Chandy R, Metwali KE (2003) Candida albicans strain carriage in patients and nursing staff of an intensive care unit: a study of morphotypes and resistotypes. Mycoses 46:479–486
    • View reference on PubMed
    • View reference on publisher's website
  28. Marco F, Lockhart SR, Pfaller MA, Pujol C, Rangel-Frausto MS, Wiblin T, Blumberg HM, Edwards JE, Jarvis W, Saiman L, Patterson JE, Rinaldi MG, Wenzel RP, Soll DR (1999) Elucidating the origins of nosocomial infections with Candida albicans by DNA fingerprinting with the complex probe Ca3. J Clin Microbiol 37:2817–2828
    • View reference on PubMed
  29. Nucci M, Anaissie E (2001) Revisiting the source of candidemia: skin or gut? Clin Infect Dis 33:1959–1967
    • View reference on PubMed
    • View reference on publisher's website
  30. Filler SG (2012) Insights from human studies into the host defense against candidiasis. Cytokine 58:129–132
    • View reference on PubMed
    • View reference on publisher's website
  31. Charlier C, Hart E, Lefort A, Ribaud P, Dromer F, Denning DW, Lortholary O (2006) Fluconazole for the management of invasive candidiasis: where do we stand after 15 years? J Antimicrob Chemother 57:384–410
    • View reference on PubMed
    • View reference on publisher's website
  32. Maertens J, Marchetti O, Herbrecht R, Cornely OA, Fluckiger U, Frere P, Gachot B, Heinz WJ, Lass-Florl C, Ribaud P, Thiebaut A, Cordonnier C, Third European Conference on Infections in Leukemia (2011) European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3–2009 update. Bone Marrow Transplant 46:709–718
    • View reference on PubMed
    • View reference on publisher's website
  33. Dannaoui E, Desnos-Ollivier M, Garcia-Hermoso D, Grenouillet F, Cassaing S, Baixench MT, Bretagne S, Dromer F, Lortholary O, French Mycoses Study G (2012) Candida spp. with acquired echinocandin resistance, France, 2004–2010. Emerg Infect Dis 18:86–90
    • View reference on PubMed
    • View reference on publisher's website
  34. Pacholczyk M, Lagiewska B, Lisik W, Wasiak D, Chmura A (2011) Invasive fungal infections following liver transplantation—risk factors, incidence and outcome. Ann Transplant 16:14–16
    • View reference on PubMed
  35. Schaenman JM (2013) Is universal antifungal prophylaxis mandatory in lung transplant patients? Curr Opin Infect Dis 26:317–325
    • View reference on PubMed
    • View reference on publisher's website
  36. Toth A, Csonka K, Jacobs C, Vagvolgyi C, Nosanchuk JD, Netea MG, Gacser A (2013) Candida albicans and Candida parapsilosis induce different T-cell responses in human peripheral blood mononuclear cells. J Infect Dis 208:690–698
    • View reference on PubMed
    • View reference on publisher's website
  37. Charles PE, Doise JM, Quenot JP, Aube H, Dalle F, Chavanet P, Milesi N, Aho LS, Portier H, Blettery B (2003) Candidemia in critically ill patients: difference of outcome between medical and surgical patients. Intensive Care Med 29:2162–2169
  38. Charles PE, Dalle F, Aube H, Doise JM, Quenot JP, Aho LS, Chavanet P, Blettery B (2005) Candida spp. colonization significance in critically ill medical patients: a prospective study. Intensive Care Med 31:393–400
  39. Eggimann P, Calandra T, Fluckiger U, Bille J, Garbino J, Glauser MP, Marchetti O, Ruef C, Tauber M, Pittet D, Fungal Infection Network of Switzerland (2005) Invasive candidiasis: comparison of management choices by infectious disease and critical care specialists. Intensive Care Med 31:1514–1521
  40. Garbino J, Lew DP, Romand JA, Hugonnet S, Auckenthaler R, Pittet D (2002) Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination. Intensive Care Med 28:1708–1717
  41. Vincent JL, Anaissie E, Bruining H, Demajo W, el-Ebiary M, Haber J, Hiramatsu Y, Nitenberg G, Nystrom PO, Pittet D, Rogers T, Sandven P, Sganga G, Schaller MD, Solomkin J (1998) Epidemiology, diagnosis and treatment of systemic Candida infection in surgical patients under intensive care. Intensive Care Med 24:206–216
  42. Solomkin JS, Flohr AB, Quie PG, Simmons RL (1980) The role of Candida in intraperitoneal infections. Surgery 88:524–530
    • View reference on PubMed
  43. Calandra T, Bille J, Schneider R, Mosimann F, Francioli P (1989) Clinical significance of Candida isolated from peritoneum in surgical patients. Lancet 2:1437–1440
    • View reference on PubMed
    • View reference on publisher's website
  44. Tissot F, Lamoth F, Hauser PM, Orasch C, Fluckiger U, Siegemund M, Zimmerli S, Calandra T, Bille J, Eggimann P, Marchetti O, Fungal Infection Network of Switzerland (FUNGINOS) (2013) Beta-glucan antigenemia anticipates diagnosis of blood culture-negative intraabdominal candidiasis. Am J Respir Crit Care Med 188:1100–1109
    • View reference on PubMed
    • View reference on publisher's website
  45. Eggimann P, Francioli P, Bille J, Schneider R, Wu MM, Chapuis G, Chiolero R, Pannatier A, Schilling J, Geroulanos S, Glauser MP, Calandra T (1999) Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Crit Care Med 27:1066–1072
    • View reference on PubMed
    • View reference on publisher's website
  46. Senn L, Eggimann P, Ksontini R, Pascual A, Demartines N, Bille J, Calandra T, Marchetti O (2009) Caspofungin for prevention of intra-abdominal candidiasis in high-risk surgical patients. Intensive Care Med 35:903–908
  47. Goldstein E, Hoeprich PD (1972) Problems in the diagnosis and treatment of systemic candidiasis. J Infect Dis 125:190–193
    • View reference on PubMed
    • View reference on publisher's website
  48. Klein JJ, Watanakunakorn C (1979) Hospital-acquired fungemia. Its natural course and clinical significance. Am J Med 67:51–58
    • View reference on PubMed
    • View reference on publisher's website
  49. Solomkin JS, Flohr AM, Simmons RL (1982) Indications for therapy for fungemia in postoperative patients. Arch Surg 117:1272–1275
    • View reference on PubMed
    • View reference on publisher's website
  50. Vazquez JA, Sanchez V, Dmuchowski C, Dembry LM, Sobel JD, Zervos MJ (1993) Nosocomial acquisition of Candida albicans: an epidemiologic study. J Infect Dis 168:195–201
    • View reference on PubMed
    • View reference on publisher's website
  51. Tran LT, Auger P, Marchand R, Carrier M, Pelletier C (1997) Epidemiological study of Candida spp. colonization in cardiovascular surgical patients. Mycoses 40:169–173
    • View reference on PubMed
    • View reference on publisher's website
  52. Yazdanparast K, Auger P, Marchand R, Carrier M, Cartier R (2001) Predictive value of Candida colonization index in 131 patients undergoing two different cardiovascular surgical procedures. J Cardiovasc Surg 42:339–343
  53. Eloy O, Marque S, Mourvilliers B, Pina P, Allouch PY, Pangon B, Bedos JP, Ghnassia JC (2006) Contribution of the Pittet’s index, antigen assay, IgM, and total antibodies in the diagnosis of invasive candidiasis in intensive care unit. J Mycol Med 16:113–118
  54. Agvald-Ohman C, Klingspor L, Hjelmqvist H, Edlund C (2008) Invasive candidiasis in long-term patients at a multidisciplinary intensive care unit: candida colonization index, risk factors, treatment and outcome. Scand J Infect Dis 40:145–153
    • View reference on PubMed
    • View reference on publisher's website
  55. Massou S, Ahid S, Azendour H, Bensghir M, Mounir K, Iken M, Lmimouni BE, Balkhi H, Drissi Kamili N, Haimeur C (2013) Systemic candidiasis in medical intensive care unit: analysis of risk factors and the contribution of colonization index. Pathol Biol (Paris) 61:108–112
    • View reference on publisher's website
  56. Chabasse D (2001) Yeast count in urine. Review of the literature and preliminary results of a multicenter prospective study carried out in 15 hospital centers. Ann Fr Anesth Reanim 20:400–406
    • View reference on PubMed
    • View reference on publisher's website
  57. Dubau B, Triboulet C, Winnock S (2001) Use of the colonization index. Ann Fr Anesth Reanim 20:418–420
    • View reference on PubMed
    • View reference on publisher's website
  58. Sellami A, Sellami H, Makni F, Bahloul M, Cheikh-Rouhou F, Bouaziz M, Ayadi A (2006) Candiduria in intensive care unit: significance and value of yeast numeration in urine. Ann Fr Anesth Reanim 25:584–588
    • View reference on PubMed
    • View reference on publisher's website
  59. Ergin F, Eren Tulek N, Yetkin MA, Bulut C, Oral B, Tuncer Ertem G (2013) Evaluation of Candida colonization in intensive care unit patients and the use of Candida colonization index. Mikrobiyol Bul 47:305–317
    • View reference on PubMed
    • View reference on publisher's website
  60. Laverdiere M, Rotstein C, Bow EJ, Roberts RS, Ioannou S, Carr D, Moghaddam N (2000) Impact of fluconazole prophylaxis on fungal colonization and infection rates in neutropenic patients. The Canadian Fluconazole Study. J Antimicrob Chemother 46:1001–1008
    • View reference on PubMed
    • View reference on publisher's website
  61. Normand S, Francois B, Darde ML, Bouteille B, Bonnivard M, Preux PM, Gastinne H, Vignon P (2005) Oral nystatin prophylaxis of Candida spp. colonization in ventilated critically ill patients. Intensive Care Med 31:1508–1513
  62. Giglio M, Caggiano G, Dalfino L, Brienza N, Alicino I, Sgobio A, Favale A, Coretti C, Montagna MT, Bruno F, Puntillo F (2012) Oral nystatin prophylaxis in surgical/trauma ICU patients: a randomised clinical trial. Crit Care 16:R57
    • View reference on PubMed
    • View reference on publisher's website
  63. Chen Z, Yang CL, He HW, Zeng J (2013) The clinical research of nystatin in prevention of invasive fungal infections in patients on mechanical ventilation in intensive care unit. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 25:475–478
    • View reference on PubMed
  64. Piarroux R, Grenouillet F, Balvay P, Tran V, Blasco G, Millon L, Boillot A (2004) Assessment of preemptive treatment to prevent severe candidiasis in critically ill surgical patients. Crit Care Med 32:2443–2449
    • View reference on PubMed
    • View reference on publisher's website
  65. Eren A, Aydogan S, Kalkanci A, Kustimur S (2007) The relationship between Candida albicans colonization indices and the presence of specific antibodies in non-neutropenic intensive care unit patients. Mikrobiyol Bul 41:253–259
    • View reference on PubMed
  66. Wang DH, Gao XJ, Wei LQ, Xia R, Sun L, Li Q, Peng M, Qin YZ (2009) The preemptive treatment of invasive Candida infection with reference of corrected colonization index in critically ill patients: a multicenter, prospective, randomized controlled clinical study. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 21:525–528
    • View reference on PubMed
  67. Leon C, Ruiz-Santana S, Saavedra P, Galvan B, Blanco A, Castro C, Balasini C, Utande-Vazquez A, Gonzalez de Molina FJ, Blasco-Navalproto MA, Lopez MJ, Charles PE, Martin E, Hernandez-Viera MA, Cava Study G (2009) Usefulness of the “Candida score” for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study. Critical Care Med 37:1624–1633
    • View reference on publisher's website
  68. Ellis M, Al-Ramadi B, Bernsen R, Kristensen J, Alizadeh H, Hedstrom U (2009) Prospective evaluation of mannan and anti-mannan antibodies for diagnosis of invasive Candida infections in patients with neutropenic fever. J Med Microbiol 58:606–615
    • View reference on PubMed
    • View reference on publisher's website
  69. Caggiano G, Puntillo F, Coretti C, Giglio M, Alicino I, Manca F, Bruno F, Montagna MT (2011) Candida colonization index in patients admitted to an ICU. Int J Mol Sci 12:7038–7047
    • View reference on PubMed
    • View reference on publisher's website
  70. Posteraro B, De Pascale G, Tumbarello M, Torelli R, Pennisi MA, Bello G, Maviglia R, Fadda G, Sanguinetti M, Antonelli M (2011) Early diagnosis of candidemia in intensive care unit patients with sepsis: a prospective comparison of (1→3)-beta-d-glucan assay, Candida score, and colonization index. Crit Care 15:R249
    • View reference on PubMed
    • View reference on publisher's website
  71. Peman J, Zaragoza R, Quindos G, Alkorta M, Cuetara MS, Camarena JJ, Ramirez P, Gimenez MJ, Martin-Mazuelos E, Linares-Sicilia MJ, Ponton J, Study group Candida albicans Germ Tube Antibody Detection in Critically Ill Patients (2011) Clinical factors associated with a Candida albicans germ tube antibody positive test in intensive care unit patients. BMC Infect Dis 11:60
    • View reference on PubMed
    • View reference on publisher's website
  72. Hall AM, Poole LA, Renton B, Wozniak A, Fisher M, Neal T, Halloran CM, Cox T, Hampshire PA (2013) Prediction of invasive candidal infection in critically ill patients with severe acute pancreatitis. Crit Care 17:R49
    • View reference on PubMed
    • View reference on publisher's website
  73. Ostrosky-Zeichner L, Shoham S, Vazquez J, Reboli A, Betts R, Barron MA, Schuster M, Judson MA, Revankar SG, Caeiro JP, Mangino JE, Mushatt D, Bedimo R, Freifeld A, Nguyen MH, Kauffman CA, Dismukes WE, Westfall AO, Deerman JB, Wood C, Sobel JD, Pappas PG (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
  74. Timsit JF, Azoulay E, Cornet M, Gangneux JP, Jullien V, Vesin A, Schir E, Wolff M (2013) EMPIRICUS micafungin versus placebo during nosocomial sepsis in Candida multi-colonized ICU patients with multiple organ failures: study protocol for a randomized controlled trial. Trials 14:399
    • View reference on PubMed
    • View reference on publisher's website
  75. Charles PE, Castro C, Ruiz-Santana S, Leon C, Saavedra P, Martin E (2009) Serum procalcitonin levels in critically ill patients colonized with Candida spp: new clues for the early recognition of invasive candidiasis? Intensive Care Med 35:2146–2150
  76. Wójtowicz A, Tissot F, Lamoth F, Orasch C, Eggimann P, Siegemund M, Zimmerli S, Flueckiger UM, Bille J, Calandra T, Marchetti M, Bochud PY (2014) Polymorphisms in TNF-α increase susceptibility to intra-abdominal candida infection in high risk surgical ICU patients. Critical Care Med 42:e304
    • View reference on publisher's website

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