Top

Published in:

Open Access 01-01-2009 | Review

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis

Authors: Benoît P. Guery, Maiken C. Arendrup, Georg Auzinger, Élie Azoulay, Márcio Borges Sá, Elizabeth M. Johnson, Eckhard Müller, Christian Putensen, Coleman Rotstein, Gabriele Sganga, Mario Venditti, Rafael Zaragoza Crespo, Bart Jan Kullberg

Published in: Intensive Care Medicine | Issue 1/2009

Abstract

Background

Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting, particularly in the intensive care unit (ICU).

Objectives and methods

To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and a European expert panel discussion.

Results and conclusions

Candida albicans remains the most frequently isolated fungal species followed by C. glabrata. The diagnosis of invasive candidiasis involves both clinical and laboratory parameters, but neither of these are specific. One of the main features in diagnosis is the evaluation of risk factor for infection which will identify patients in need of pre-emptive or empiric treatment. Clinical scores were built from those risk factors. Among laboratory diagnosis, a positive blood culture from a normally sterile site provides positive evidence. Surrogate markers have also been proposed like 1,3 β-d glucan level, mannans, or PCR testing. Invasive candidiasis and candidemia is a growing concern in the ICU, apart from cases with positive blood cultures or fluid/tissue biopsy, diagnosis is neither sensitive nor specific. The diagnosis remains difficult and is usually based on the evaluation of risk factors.

Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24, 179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39:309–317PubMedCrossRef

Pfaller MA, Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20:133–163PubMedCrossRef

Arendrup MC, Fuursted K, Gahrn-Hansen B, Jensen IM, Knudsen JD, Lundgren B, Schonheyder HC, Tvede M (2005) Seminational surveillance of fungemia in Denmark: notably high rates of fungemia and numbers of isolates with reduced azole susceptibility. J Clin Microbiol 43:4434–4440PubMedCrossRef

Arendrup MC, Fuursted K, Gahrn-Hansen B, Schonheyder HC, Knudsen JD, Jensen IM, Bruun B, Christensen JJ, Johansen HK (2008) Semi-national surveillance of fungaemia in Denmark 2004–2006: increasing incidence of fungaemia and numbers of isolates with reduced azole susceptibility. Clin Microbiol Infect 14:487–494PubMedCrossRef

Poikonen E, Lyytikainen O, Anttila VJ, Ruutu P (2003) Candidemia in Finland, 1995–1999. Emerg Infect Dis 9:985–990PubMed

Luzzati R, Allegranzi B, Antozzi L, Masala L, Pegoraro E, Azzini A, Concia E (2005) Secular trends in nosocomial candidaemia in non-neutropenic patients in an Italian tertiary hospital. Clin Microbiol Infect 11:908–913PubMedCrossRef

Bougnoux ME, Kac G, Aegerter P, d’Enfert C, Fagon JY (2008) Candidemia and candiduria in critically ill patients admitted to intensive care units in France: incidence, molecular diversity, management and outcome. Intensive Care Med 34:292–299PubMedCrossRef

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

Rentz AM, Halpern MT, Bowden R (1998) The impact of candidemia on length of hospital stay, outcome, and overall cost of illness. Clin Infect Dis 27:781–788PubMedCrossRef

10.

Olaechea PM, Palomar M, Leon-Gil C, Alvarez-Lerma F, Jorda R, Nolla-Salas J, Leon-Regidor MA (2004) Economic impact of Candida colonization and Candida infection in the critically ill patient. Eur J Clin Microbiol Infect Dis 23:323–330PubMedCrossRef

11.

Marchetti O, Bille J, Fluckiger U, Eggimann P, Ruef C, Garbino J, Calandra T, Glauser MP, Tauber MG, Pittet D (2004) Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991–2000. Clin Infect Dis 38:311–320PubMedCrossRef

12.

Gudlaugsson O, Gillespie S, Lee K, Vande BJ, Hu J, Messer S, Herwaldt L, Pfaller M, Diekema D (2003) Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis 37:1172–1177PubMedCrossRef

13.

Hadley S, Lee WW, Ruthazer R, Nasraway SA Jr (2002) Candidemia as a cause of septic shock and multiple organ failure in nonimmunocompromised patients. Crit Care Med 30:1808–1814PubMedCrossRef

14.

Falagas ME, Apostolou KE, Pappas VD (2006) Attributable mortality of candidemia: a systematic review of matched cohort and case-control studies. Eur J Clin Microbiol Infect Dis 25:419–425PubMedCrossRef

15.

Tumbarello M, Posteraro B, Trecarichi EM, Fiori B, Rossi M, Porta R, de Gaetano DK, La Sorda M, Spanu T, Fadda G, Cauda R, Sanguinetti M (2007) Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia. J Clin Microbiol 45:1843–1850PubMedCrossRef

16.

Dimopoulos G, Ntziora F, Rachiotis G, Armaganidis A, Falagas ME (2008) Candida albicans versus non-albicans intensive care unit-acquired bloodstream infections: differences in risk factors and outcome. Anesth Analg 106:523–529PubMedCrossRef

17.

Blot S, Vandewoude K, Hoste E, Poelaert J, Colardyn F (2001) Outcome in critically ill patients with candidal fungaemia: Candida albicans vs. Candida glabrata. J Hosp Infect 47:308–313PubMedCrossRef

18.

Viscoli C, Girmenia C, Marinus A, Collette L, Martino P, Vandercam B, Doyen C, Lebeau B, Spence D, Krcmery V, De Pauw B, Meunier F (1999) Candidemia in cancer patients: a prospective, multicenter surveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC). Clin Infect Dis 28:1071–1079PubMedCrossRef

19.

Kovacicova G, Krupova Y, Lovaszova M, Roidova A, Trupl J, Liskova A, Hanzen J, Milosovic P, Lamosova M, Macekova L, Szovenyiova Z, Purgelova A, Obertik T, Bille J, Krcmery V (2000) Antifungal susceptibility of 262 bloodstream yeast isolates from a mixed cancer and non-cancer patient population: is there a correlation between in-vitro resistance to fluconazole and the outcome of fungemia? J Infect Chemother 6:216–221PubMedCrossRef

20.

Klevay MJ, Ernst EJ, Hollanbaugh JL, Miller JG, Pfaller MA, Diekema DJ (2008) Therapy and outcome of Candida glabrata versus Candida albicans bloodstream infection. Diag Microbiol Infect Dis 60:273–277CrossRef

21.

Aliyu SH, Enoch DA, Abubakar II, Ali R, Carmichael AJ, Farrington M, Lever AM (2006) Candidaemia in a large teaching hospital: a clinical audit. QJM 99:655–663PubMedCrossRef

22.

Bassetti M, Righi E, Costa A, Fasce R, Molinari MP, Rosso R, Pallavicini FB, Viscoli C (2006) Epidemiological trends in nosocomial candidemia in intensive care. BMC Infect Dis 6:21PubMedCrossRef

23.

Shorr AF, Lazarus DR, Sherner JH, Jackson WL, Morrel M, Fraser VJ, Kollef MH (2007) Do clinical features allow for accurate prediction of fungal pathogenesis in bloodstream infections? Potential implications of the increasing prevalence of non-albicans candidemia. Crit Care Med 35:1077–1083PubMedCrossRef

24.

Kibbler CC, Seaton S, Barnes RA, Gransden WR, Holliman RE, Johnson EM, Perry JD, Sullivan DJ, Wilson JA (2003) Management and outcome of bloodstream infections due to Candida species in England and Wales. J Hosp Infect 54:18–24PubMedCrossRef

25.

Tortorano AM, Peman J, Bernhardt H, Klingspor L, Kibbler CC, Faure O, Biraghi E, Canton E, Zimmermann K, Seaton S, Grillot R (2004) Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study. Eur J Clin Microbiol Infect Dis 23:317–322PubMedCrossRef

26.

Comert F, Kulah C, Aktas E, Eroglu O, Ozlu N (2007) Identification of Candida species isolated from patients in intensive care unit and in vitro susceptibility to fluconazole for a 3-year period. Mycoses 50:52–57PubMedCrossRef

27.

Laverdiere M, Labbe AC, Restieri C, Rotstein C, Heyland D, Madger S, Stewart T (2007) Susceptibility patterns of Candida species recovered from Canadian intensive care units. J Crit Care 22:245–250PubMedCrossRef

28.

Leon C, Ruiz-Santana S, Saavedra P, Almirante B, Nolla-Salas J, Alvarez-Lerma F, Garnacho-Montero J, Leon MA (2006) A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med 34:730–737PubMedCrossRef

29.

Fluckiger U, Marchetti O, Bille J, Eggimann P, Zimmerli S, Imhof A, Garbino J, Ruef C, Pittet D, Tauber M, Glauser M, Calandra T (2006) Treatment options of invasive fungal infections in adults. Swiss Med Wkly 136:447–463PubMed

30.

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 49:3640–3645PubMedCrossRef

31.

Spellberg BJ, Filler SG, Edwards JE Jr (2006) Current treatment strategies for disseminated candidiasis. Clin Infect Dis 42:244–251PubMedCrossRef

32.

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 43:235–243PubMedCrossRef

33.

Ostrosky-Zeichner L, Sable C, Sobel J, Alexander BD, Donowitz G, Kan V, Kauffman CA, Kett D, Larsen RA, Morrison V, Nucci M, Pappas PG, Bradley ME, Major S, Zimmer L, Wallace D, Dismukes WE, Rex JH (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 26:271–276PubMedCrossRef

34.

Blumberg HM, Jarvis WR, Soucie JM, Edwards JE, Patterson JE, Pfaller MA, Rangel-Frausto MS, Rinaldi MG, Saiman L, Wiblin RT, Wenzel RP (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 33:177–186PubMedCrossRef

35.

Sobel JD, Rex JH (2001) Invasive candidiasis: turning risk into a practical prevention policy? Clin Infect Dis 33:187–190PubMedCrossRef

36.

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

37.

De Waele JJ, Vogelaers D, Blot S, Colardyn F (2003) Fungal infections in patients with severe acute pancreatitis and the use of prophylactic therapy. Clin Infect Dis 37:208–213PubMedCrossRef

38.

Dupont H, Paugam-Burtz C, Muller-Serieys C, Fierobe L, Chosidow D, Marmuse JP, Mantz J, Desmonts JM (2002) Predictive factors of mortality due to polymicrobial peritonitis with Candida isolation in peritoneal fluid in critically ill patients. Arch Surg 137:1341–1346PubMedCrossRef

39.

Agvald-Ohman C, Klingspor L, Hjelmqvist H, Edlund C (2007) Invasive candidiasis in long-term patients at a multidisciplinary intensive care unit: Candida colonization index, risk factors, treatment and outcome. Scand J Infect Dis 40:145–153CrossRef

40.

Munoz P, Burillo A, Bouza E (2000) Criteria used when initiating antifungal therapy against Candida spp. in the intensive care unit. Int J Antimicrob Agents 15:83–90PubMedCrossRef

41.

Pelz RK, Lipsett PA, Swoboda SM, Diener-West M, Hammond JM, Hendrix CW (2000) The diagnostic value of fungal surveillance cultures in critically ill patients. Surg Infect (Larchmt) 1:273–281CrossRef

42.

Michalopoulos AS, Geroulanos S, Mentzelopoulos SD (2003) Determinants of candidemia and candidemia-related death in cardiothoracic ICU patients. Chest 124:2244–2255PubMedCrossRef

43.

Petri MG, Konig J, Moecke HP, Gramm HJ, Barkow H, Kujath P, Dennhart R, Schafer H, Meyer N, Kalmar P, Thulig P, Muller J, Lode H (1997) Epidemiology of invasive mycosis in ICU patients: a prospective multicenter study in 435 non-neutropenic patients. Paul-Ehrlich Society for Chemotherapy, Divisions of Mycology and Pneumonia Research. Intensive Care Med 23:317–325PubMedCrossRef

44.

Stephan F, Bah MS, Desterke C, Rezaiguia-Delclaux S, Foulet F, Duvaldestin P, Bretagne S (2002) Molecular diversity and routes of colonization of Candida albicans in a surgical intensive care unit, as studied using microsatellite markers. Clin Infect Dis 35:1477–1483PubMedCrossRef

45.

Eloy O, Marque S, Botterel F, Stephan F, Costa JM, Lasserre V, Bretagne S (2006) Uniform distribution of three Candida albicans microsatellite markers in two French ICU populations supports a lack of nosocomial cross-contamination. BMC Infect Dis 6:162PubMedCrossRef

46.

Pittet D, Monod M, Suter PM, Frenk E, Auckenthaler R (1994) Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg 220:751–758PubMedCrossRef

47.

Ostrosky-Zeichner L, Alexander BD, Kett DH, Vazquez J, Pappas PG, Saeki F, Ketchum PA, Wingard J, Schiff R, Tamura H, Finkelman MA, Rex JH (2005) Multicenter clinical evaluation of the (1–>3) beta-d-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis 41:654–659PubMedCrossRef

48.

Fukazawa Y (1989) Antigenic structure of Candida albicans. Immunochemical basis of the serologic specificity of the mannans in yeasts. Immunol Ser 47:37–62PubMed

49.

Poulain D, Robert R, Mesnard F, Sendid B, Lepage G, Camus D (1997) Clearances of Candida albicans-derived alpha- and beta-linked mannose residues in sera from patients with candidiasis. Eur J Clin Microbiol Infect Dis 16:16–20PubMedCrossRef

50.

Sendid B, Tabouret M, Poirot JL, Mathieu D, Fruit J, Poulain D (1999) New enzyme immunoassays for sensitive detection of circulating Candida albicans mannan and antimannan antibodies: useful combined test for diagnosis of systemic candidiasis. J Clin Microbiol 37:1510–1517PubMed

51.

Sendid B, Poirot JL, Tabouret M, Bonnin A, Caillot D, Camus D, Poulain D (2002) Combined detection of mannanaemia and antimannan antibodies as a strategy for the diagnosis of systemic infection caused by pathogenic Candida species. J Med Microbiol 51:433–442PubMedCrossRef

52.

Sendid B, Jouault T, Coudriau R, Camus D, Odds F, Tabouret M, Poulain D (2004) Increased sensitivity of mannanemia detection tests by joint detection of alpha- and beta-linked oligomannosides during experimental and human systemic candidiasis. J Clin Microbiol 42:164–171PubMedCrossRef

53.

Moragues MD, Ortiz N, Iruretagoyena JR, Garcia-Ruiz JC, Amutio E, Rojas A, Mendoza J, Quindos G, Ponton-San Emeterio J (2004) Evaluation of a new commercial test (Candida albicans IFA IgG) for the serodiagnosis of invasive candidiasis. Enferm Infecc Microbiol Clin 22:83–88PubMed

54.

Lain A, Elguezabal N, Brena S, Garcia-Ruiz JC, Del Palacio A, Moragues MD, Ponton J (2007) Diagnosis of invasive candidiasis by enzyme-linked immunosorbent assay using the N-terminal fragment of Candida albicans hyphal wall protein 1. BMC Microbiol 7:35PubMedCrossRef

55.

Arishima T, Takezawa J (2006) Use of PCR based diagnosis for common invasive fungal infections in the intensive care unit. Nippon Ishinkin Gakkai Zasshi 47:283–288PubMedCrossRef

56.

McMullan R, Metwally L, Coyle PV, Hedderwick S, McCloskey B, O’Neill HJ, Patterson CC, Thompson G, Webb CH, Hay RJ (2008) A prospective clinical trial of a real-time polymerase chain reaction assay for the diagnosis of candidemia in nonneutropenic, critically ill adults. Clin Infect Dis 46:890–896PubMedCrossRef

Title: Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis
Authors: Benoît P. Guery
Maiken C. Arendrup
Georg Auzinger
Élie Azoulay
Márcio Borges Sá
Elizabeth M. Johnson
Eckhard Müller
Christian Putensen
Coleman Rotstein
Gabriele Sganga
Mario Venditti
Rafael Zaragoza Crespo
Bart Jan Kullberg
Publication date: 01-01-2009
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 1/2009
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-008-1338-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis

Abstract

Background

Objectives and methods

Results and conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objectives and methods

Results and conclusions

Please log in to get access to this content

Other articles of this Issue 1/2009

Incidence and prognostic value of right ventricular failure in acute respiratory distress syndrome

Heart rate and leukocytes after air and ground transportation in artificially ventilated neonates: a prospective observational study

Previous endotracheal aspirate allows guiding the initial treatment of ventilator-associated pneumonia

Intensive insulin therapy: enhanced Model Predictive Control algorithm versus standard care

Valsalva, Valsalva, may you give me a clue, who needs fluids in my ICU?

Response to hypercapnic challenge is associated with successful weaning from prolonged mechanical ventilation due to brain stem lesions