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Epidemiology, diagnosis and treatment of systemic Candida infection in surgical patients under intensive care

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Abstract

The incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years as a result of a combination of factors. More patients with severe underlying disease or immunosuppression from anti-neoplastic or anti-rejection chemotherapy and at risk from fungal infection are now admitted to the ICU. Improvements in supportive medical and surgical care have led to many patients who would previously have died as a result of trauma or disease surviving to receive intensive care. Moreover, some therapeutic interventions used in the ICU, most notably broad-spectrum antibiotics and intravascular catheters, are also associated with increased risks of candidiasis. Systemic Candida infections are associated with a high morbidity and mortality, but remain difficult to diagnose and ICU staff need to bé acutely aware of this often insidious pathogen. A number of studies have identified risk factors for systemic Candida infection which may be used to identify those at highest risk. Such patients may be potential candidates for early, presumptive therapy. Here we review the epidemiology, pathogenesis, morbidity and mortality of systemic Candida infections in the ICU setting, and examine predisposing risk factors. Antifungal treatment, including the use of amphotericin B, flucytosine and fluconazole, and the roles of early presumptive therapy and prophylaxis, is also reviewed.

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References

  1. Schaberg DR, Culver DH, Gaynes RP (1991) Major trends in the microbial etiology of nosocomial infection. Am J Med 91 (Suppl 3B): 72S-75S

    Article  PubMed  CAS  Google Scholar 

  2. Jarvis WR, Martone WJ (1992) Predominant pathogens in hospital infections. J Antimicrob Chemother 29 (Suppl A): 19–24

    Article  PubMed  Google Scholar 

  3. Beck-Sagué C, Jarvis WR (1993) Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980–1990. J Infect Dis 167: 1247–1251

    Article  PubMed  Google Scholar 

  4. Bodey GP (1993) Hematogenous and major organ candidiasis. In: Bodey GP (ed) Candidiasis: Pathogenesis, diagnosis and treatment. Raven Press, New York, pp 279–329

    Google Scholar 

  5. Franklin C, Metry M (1992) Life-threatening Candida infections in the intensive care unit. J Intensive Care Med 7: 127–137

    Google Scholar 

  6. Banerjee SN, Emori TG, Culver DH, Gaynes RP, Jarvis WR, Horan T et al. (1991) Secular trends in nosocomial primary bloodstream infections in the United States. Am J Med 91 (Suppl 3B): 86S-89S

    Article  PubMed  CAS  Google Scholar 

  7. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM (1988) CDC definitions for nosocomial infections. Am J Infect Control 16:128–140

    Article  PubMed  CAS  Google Scholar 

  8. Vincent JL, Bihari DJ, Suter PM, Bruining HA, White J, Nicolas-Chanoine M-H, Wolff M, Spencer RC, Hemmer MD (1995) The prevalence of nosocomial infection in intensive care units in Europe (EPIC). JAMA 274: 639–644

    Article  PubMed  CAS  Google Scholar 

  9. Brooks RG (1989) Prospective study of Candida endophthalmitis in hospitalized patients with candidemia. Arch Intern Med 149: 2226–2228

    Article  PubMed  CAS  Google Scholar 

  10. Menezes AV, Sigesmund DA, Demajo WA, Devenyi RG (1994) Mortality of hospitalized patients with Candida endophthalmitis. Arch Intern Med 154: 2093–2097

    Article  PubMed  CAS  Google Scholar 

  11. Horn R, Wong B, Kiehn TE, Armstrong D (1985) Fungemia in a cancer hospital: changing frequency, earlier onset and results of therapy. Rev Infect Dis 7: 646–655

    Article  PubMed  CAS  Google Scholar 

  12. Wey SB, Motomi M, Pfaller MA, Woolson RF, Wenzel RP (1988) Hospital-acquired candidemia: the attributable mortality and excess length of stay. Arch Intern Med 148:2642–2645

    Article  PubMed  CAS  Google Scholar 

  13. Bross J, Talbot GH, Maislin G, Hurwits S, Strom BL (1989) Risk factors for nosocomial candidemia: a case-control study in adults without leukemia. Am J Med 87: 614–620

    Article  PubMed  CAS  Google Scholar 

  14. Pittet D (1993) Nosocomial bloodstream infections. In: Wenzel RP (ed) Prevention and Control of Nosocomial Infections, 2nd Edn. Williams and Wilkins, Baltimore, pp 512–555

    Google Scholar 

  15. Edwards JE Jr (1990) Candida species. In: Mandell GL, Douglas RG Jr, Bennett JE (eds) Principles and practice of infectious disease, 3rd Edn. Churchill Livingstone, New York, pp 1943–1958

    Google Scholar 

  16. Odds FC (1988) Candida and candidosis. Balliére Tindall, London

    Google Scholar 

  17. Hoeprich PD, Rinaldi MG (1989) Candidosis. In: Hoeprich PD, Jordan MC (eds) Infectious diseases, a modern treatise of infectious processes. Lippincott, Philadelphia, pp 465–481

    Google Scholar 

  18. Rotstein O, Pruett T, Simmons R (1986) Microbiologic features and treatment of persistent peritonitis in patients in the intensive care unit. Can J Surg 29:247–250

    PubMed  CAS  Google Scholar 

  19. Marshall J, Christou N, Norn R, Meakins J (1988) The microbiology of multiple organ failure. The proximal gastrointestinal tract as an occult reservoir of pathogens. Arch Surg 123: 309–315

    Article  PubMed  CAS  Google Scholar 

  20. Richet HM, Andremont A, Tancrede C, Pico JL, Jarvis WR (1991) Risk factors of candidemia in patients with acute lymphocytic leukemia. Rev Infect Dis 13: 211–215

    Article  PubMed  CAS  Google Scholar 

  21. Pittet D, Monod M, Filthuth I, Frenk E, Suter PM, Auckenthaler R (1991) Contour-clamped homogenous electric field gel electrophoresis as a powerful epidemiologic tool in yeast infections. Am J Med 91 (Suppl 3B): 256S-263S

    Article  PubMed  CAS  Google Scholar 

  22. Voss A, Hollis RJ, Pfaller MA, Wenzel RP, Doebbeling BN (1994) Investigation of the sequence of colonization and candidemia in non-neutropenic patients. J Clin Microbiol 32: 975–980

    PubMed Central  PubMed  CAS  Google Scholar 

  23. Solomkin JS (1993) Pathogenesis and management of Candida infection syndromes in non-neutropenic patients. New Horizons 1: 202–213

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Alexander J, Gianotti L, Pyles T, Carey M, Babcock G (1991) Distribution of Escherichia coli translocating from the intestine after thermal injury. Ann Surg 213:558–567

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Deitch EA, Bridges W, Baker J, Ma JW, Ma L, Grisham MB, Granger DN, Specian RD, Berg R (1988) Hemorrhagic shock induced bacterial translocation is reduced by xanthine oxidase inhibition or inactivation. Surgery 104:191–198

    PubMed  CAS  Google Scholar 

  27. Alverdy J (1991) The effect of glucocorticoid administration on bacterial translocation. Evidence for an aquired mucosal immunodeficient state. Ann Surg 214:719–723

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Langer JC, Sohal SS (1992) Increased mucosal permeability after intestinal ischemia-reperfusion injury is mediated by local tissue factors. J Pediatr Surg 27:239–241

    Google Scholar 

  29. Salzman AL, Wollert PS, Wang H, Menconi MJ, Youssef ME, Compton CC, Fink MP (1993) Intraluminal oxygenation ameliorates ischaemia/reperfusion-induced gut mucosal hyperpermeability in pigs. Circ Shock 40: 37–46

    PubMed  CAS  Google Scholar 

  30. Gianotti L, Alexander J, Fukushima R, Childress C (1993) Translocation of Candida albicans is related to the blood flow of individual intestinal villi. Circ Shock 40: 250–257

    PubMed  CAS  Google Scholar 

  31. Spaeth G, Gottwald T, Specian RD, Mainous MR, Berg RD, Deitch EA (1994) Secretory immunoglobulin A, intestinal mucin and mucosal permeability in nutritionally induced bacterial translocation in rats. Ann Surg 220: 798–808

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  32. Sganga G, Gangeri G, Montemagno S, Castagneto M (1995) Prevention of translocation — prevention of multiple organ system failure. In: Mutz NJ, Koller W, and Benzer H (eds) Proceedings of the 7th European Congress on Intensive Care Medicine, Innsbruck, Austria, June 14–17 1994. Monduzzi Editore S.p. A., Bologna, pp 93–101

    Google Scholar 

  33. 33. Burnie JP, Odds FC, Lee W, Webster C, Williams JD (1985) Outbreak of systemic Candida albicans in intensive care unit caused by cross infection. BMJ 290: 746–748

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  34. Vaudry WL, Tierney AJ, Wenman WM (1988) Investigation of a cluster of systemic Candida albicans infections in a neonatal intensive care unit. J Infect Dis 158:1375–1379

    Article  PubMed  CAS  Google Scholar 

  35. Matthews R, Burnie J (1989) Assessment of DNA fingerprinting for rapid identification of outbreaks of systemic candidiasis. BMJ 298: 364–375

    Article  Google Scholar 

  36. Stevens DA, Odds FC, Scherer S (1990) Application of DNA typing methods to Candida albicans epidemiology and correlations with phenotype. Rev Infect Dis 12:258–266

    Article  PubMed  CAS  Google Scholar 

  37. Romano F, Ribera G, Giuliano M (1994) A study of a hospital cluster of systemic candidosis using DNA typing methods. Epidemiol Infect 112:393–398

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  38. Rangel-Frausto MS, Martin MA, Saiman L, Blumberg H, Paterson JE, Pfaller MA, Wenzel RP, and the NEMIS study group (4–7 October 1994) High prevalence of Candida spp. on hands of healthcare workers in surgical and neonatal intensive care units: a multicenter study. Presented at 34th ICAAC, Orlando, Florida, USA, Abstract J106

  39. Rex H, Bennett JE, Sugar AM, Pappas PG, Van der Horst CM, Edwards JE, Washburn RG, Scheid M, Karchmer AW, Dine AP, Levenstein MJ, Webb CD (1994) A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. N Engl J Med 331:1325–1330

    Article  PubMed  CAS  Google Scholar 

  40. Solomon SL, Khabbaz RF, Parker RH, Bodey GP (1984) An outbreak of Candida parapsilosis bloodstream infections in patients receiving parenteral nutrition. J Infect Dis 149: 98–102

    Article  PubMed  CAS  Google Scholar 

  41. Weems JJ Jr, Chamberland ME, Ward J, Willy M, Padhye AA, Solomon SL (1987) Candida parapsilosis fungemia associated with parenteral nutrition and contaminated blood pressure transducers. J Clin Microbiol 25:1029–1032

    PubMed Central  PubMed  Google Scholar 

  42. Lee W, Burnie JP, Matthews RC, Oppenheim BO, Damani NN (1991) Hospital outbreaks with yeasts. J Hosp Infect 18 (Suppl A): 237–249

    Article  PubMed  Google Scholar 

  43. Isenberg DD, Tucci V, Cintron F, Singer C, Weinstein GS, Tyras DH (1989) Single-source outbreak of Candida tropicalis complicating coronary bypass surgery. J Clin Microbiol 27: 2426–2428

    PubMed Central  PubMed  CAS  Google Scholar 

  44. Pittet D, Garbino J (1995) Fungal infections in the critically ill. Curr Opin Crit Care 1:369–380

    Article  Google Scholar 

  45. Donahue SP, Greven CM, Zuravleff JJ, Eller AW, Nguyen MH, Peacock JEJ, Wagener MW, Yu LV (1994) Intraocular candidiasis in patients with candidemia: clinical implications derived from a prospective multicenter study. Ophthalmology 101:1302–1309

    Article  PubMed  CAS  Google Scholar 

  46. Anaissie E, Solomkin JS (1994) Fungal Infection. In: Care of the surgical patient. Scientific American Medical, New York, pp 1–19

    Google Scholar 

  47. Wey SB, Motomi M, Pfaller MA, Woolson RF, Wenzel RP (1989) Risk factors for hospital-acquired candidemia: a matched case-control study. Arch Intern Med 149: 2349–2353

    Article  PubMed  CAS  Google Scholar 

  48. Martino P, Girmenia C, Venditti M, Micozzi A, Santilli S, Burgio VL, Mandelli F (1989) Candida colonization and systemic infection in neutropenic patients. A retrospective study. Cancer 64: 2030–2034

    Article  PubMed  CAS  Google Scholar 

  49. Martino P, Girmenia C, Micozzi A, Raccah R, Gentile G, Venditti M, Mandelli F (1993) Fungemia in patients with leukemia. Am J Med Sci 306: 225–232

    Article  PubMed  CAS  Google Scholar 

  50. Karabinis A, Hill C, Leclercq B, Tancrede C, Baume D, Andremont A (1988) Risk factors for candidemia in cancer patients: a case-control study. J Clin Microbiol 26: 429–432

    PubMed Central  PubMed  CAS  Google Scholar 

  51. Pappu-Katikaneni H, Rao KP, Banister E (1990) Gastrointestinal colonization with yeast species and Candida septicemia in very low birth weight infants. Mycoses 33: 20–23

    PubMed  CAS  Google Scholar 

  52. 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: 414–421

    Article  PubMed  CAS  Google Scholar 

  53. Giuliano M, Barza M, Jacobus NV, Gorbach SL (1987) Effect of broad-spectrum parenteral antibiotics on composition of intestinal microflora of humans. Antimicrob Agents Chemother 31:202–206

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  54. Kennedy MJ, Volz PA (1985) Effect of various antibiotics on gastrointestinal colonization and dissemination by Candida albicans. Sabouradia 23: 265–273

    Article  CAS  Google Scholar 

  55. Samonis G, Anaissie EJ, Bodey GP (1990) Effects of broad-spectrum antimicrobial agents on yeast colonization of the gastrointestinal tracts of mice. Antimicrob Agents Chemother 34: 2420–2422

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  56. Samonis G, Gikas A, Anaissie EJ, Vrenzos G, Maraki S, Tselentis Y, Bodey GP (1993) Prospective evaluation of effects of broad-spectrum antibiotics on gastrointestinal yeast colonization of humans. Antimicrob Agents Chemother 37: 51–53

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  57. Ellis CA, Spivack ML (1967) The significance of candidemia. Ann Intern Med 67:511–513

    Article  PubMed  CAS  Google Scholar 

  58. Toala P, Schroeder SA, Daly AK, Finland M (1970) Candida at Boston City Hospital. Clinical and epidemiological characteristics and susceptibility to eight antimicrobial agents. Arch Intern Med 126: 983–989

    Article  PubMed  CAS  Google Scholar 

  59. Edwards JE Jr (1991) Invasive Candida infections — evolution of a fungal pathogen. N Engl J Med 324:1060–1062

    Article  PubMed  Google Scholar 

  60. Bodey GP (1993) Antifungal agents. In: Bodey GP (ed) Candidiasis: Pathogenesis, diagnosis and treatment. Raven Press, New York, pp 371–406

    Google Scholar 

  61. Solomkin JS, Flohr A, Simmons RL (1982) Candida infections in surgical patients. Dose requirements and toxicity of amphotericin B. Ann Surg 195: 177–185

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  62. Medoff G (1987) Controversial areas in antifungal chemotherapy: short-course and combination therapy with amphotericin B. Rev Infect Dis 9: 403–407

    Article  PubMed  CAS  Google Scholar 

  63. Khoo SH, Bond J, Denning DW (1994) Administering amphotericin B — a practical approach. J Antimicrob Chemother 33:203–213

    Article  PubMed  CAS  Google Scholar 

  64. Lopes-Berestein G, Hopfer RL, Mehta R, Mehta K, Hersh EM, Juliano RL (1984) Liposome-encapsulated amphotericin B for treatment of disseminated candidiasis in neutropenic mice. J Infect Dis 150: 278–283

    Article  Google Scholar 

  65. Lopes-Berestein G, Fainstein V, Hopfer RL, Mehta K, Sullivan MP, Keating M, Juliano RL (1985) Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer. J Infect Dis 151: 704–710

    Article  Google Scholar 

  66. Garbino J, Pittet D (1997) Candida infections in the ICU. Clin Intensive Care 8:187–200

    Article  Google Scholar 

  67. Anaissie EJ, Vartivarian SE, Abi-Said D, Uzun O, Pinczowski H, Kontoyiannis DP, Khoury P, Papadakis K, Gardner A, Raad II, Gilbreath J, Bodey GP (1996) Fluconazole versus amphotericin B in the treatment of hematogenous candidiasis: a matched cohort study. Am J Med 101:170–176

    Article  Google Scholar 

  68. Anaissie EJ, Darouiche R, Mera J, Gentry L, Abi-Said D, Bodey GP (1996) Management of invasive candidal infections: results of a prospective randomized multicenter study of fluconazole versus amphotericin B and review of literature. Clin Infect Dis 23: 964–972

    Article  Google Scholar 

  69. Kaufmann CA, Bradley SF, Ross SC, Weber DR (1991) Hepatosplenic candidiasis. Successful treatment with fluconazole. Am J Med 91:137–141

    Article  Google Scholar 

  70. Anaissie EJ, Bodey GP, Kantarjian H, David C, Barnett K, Bow E, Defelice R, Downs N, File T, Karam G, Potts D, Shelton M, Sugar A (1991) Fluconazole therapy for chronic disseminated candidiasis in patients with leukemia and prior amphotericin B therapy. Am J Med 91:142–150

    Article  PubMed  CAS  Google Scholar 

  71. British Society for Antimicrobial Chemotherapy (1994) Management of deep Candida infection in surgical and intensive care unit patients. Intensive Care Med 20: 522–528

    Article  Google Scholar 

  72. Pittet D, Anaissie E, Solomkin JS (1996) When to start antifungal therapy in the non-neutropenic critically ill? In: Vincent J-L (ed) Yearbook of Intensive Care and Emergency Medicine 1996. Springer, Berlin Heidelberg, pp 567–577

    Google Scholar 

  73. Singh N, Mieles L, Yu VL, Gayowski T (1993) Invasive aspergillosis in liver transplant recipients: association with candidemia and consumption coagulopathy and failure of prophylaxis with low-dose amphotericin B. Clin Infect Dis 17: 906–908

    Article  PubMed  CAS  Google Scholar 

  74. Mora NP, Cofer JB, Solomon H, Goldstein RM, Gonwa TA, Husberg BS, Klintmalm GB (1991) Analysis of severe infections (INF) after 180 consecutive liver transplants: the impact of amphotericin B prophylaxis for reducing the incidence and severity of fungal infections. Transplant Proc 23:1528–1530

    PubMed  CAS  Google Scholar 

  75. Tollemar J, Ringden O, Andersson S, Sundberg B, Ljungman P, Tyden G (1993) Randomized double-blind study of liposomal amphotericin B (AmBisome®) prophylaxis of invasive fungal infections in bone marrow transplant recipients. Bone Marrow Transplant 12:577–582

    PubMed  CAS  Google Scholar 

  76. Kung N, Fisher N, Gunson B, Hastings M, Mutimer D (1995) Fluconazole prophylaxis for high-risk liver transplant recipients. Lancet 345:1234–1235

    Article  PubMed  CAS  Google Scholar 

  77. Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H et al. (1992) A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 326: 845–851

    Article  PubMed  CAS  Google Scholar 

  78. Winston DJ, Chandrasekar PH, Lazarus HM, Goodman JL, Silber JL, Horowitz H et al. (1993) Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled double-blind multicenter trial. Ann Intern Med 118: 495–503

    Article  PubMed  CAS  Google Scholar 

  79. Bodey GP, Anaissie EJ, Elting LS, Esstey E, O’Brien S, Kantarjian H (1994) Antifungal prophylaxis during remission induction therapy for acute leukemia. Fluconazole versus intravenous amphotericin B. Cancer 73: 2099–2106

    Article  PubMed  CAS  Google Scholar 

  80. Meunier F, Aoun M, Janssens M, Dekoster C, Paesmans M (1991) Chemoprophylaxis of fungal infections in granulocytopenic patients using fluconazole vs oral amphotericin B. Drug Invest 3: 258–265

    Article  Google Scholar 

  81. Ellis ME, Clink H, Ernst P, Halim MA, Padmos A, Spence D et al. (1994) Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients. Eur J Clin Microbiol Infect Dis 13: 3–11

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Intensive Care, Erasme University Hospital, Route de Lennik, 808, B-1070, Brussels, Belgium

    J. L. Vincent, E. Anaissie, H. Bruining, W. Demajo, M. El-Ebiary, J. Haber, Y. Hiramatsu, G. Nitenberg, P. O. Nyström, D. Pittet, T. Rogers, P. Sandven, G. Sganga, M. D. Schaller & J. Solomkin

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  1. J. L. Vincent
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  2. E. Anaissie
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  3. H. Bruining
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Supported by an unrestricted educational grant from Pfizer Inc.

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Vincent, J.L., Anaissie, E., Bruining, H. et al. Epidemiology, diagnosis and treatment of systemic Candida infection in surgical patients under intensive care. Intensive Care Med 24, 206–216 (1998). https://doi.org/10.1007/s001340050552

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