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Critical Care
Published in: Critical Care 1/2016

Open Access 01-12-2016 | Review

Diagnosis and management of invasive candidiasis in the ICU: an updated approach to an old enemy

Authors: Thierry Calandra, Jason A. Roberts, Massimo Antonelli, Matteo Bassetti, Jean-Louis Vincent

Published in: Critical Care | Issue 1/2016

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Abstract

Invasive fungal infections, particularly those caused by Candida species, are not uncommon in critically ill patients and are associated with considerable morbidity and mortality. Diagnosis and management of these infections can be challenging. In this review, we will briefly discuss recent epidemiological data on invasive candidiasis and current diagnostic approaches before concentrating on antifungal treatments.
Literature
1.
Montagna MT, Caggiano G, Lovero G, De Giglio O, Coretti C, Cuna T, et al. Epidemiology of invasive fungal infections in the intensive care unit: results of a multicenter Italian survey (AURORA Project). Infection. 2013;41:645–53.CrossRefPubMedPubMedCentral
2.
Burghi G, Lemiale V, Seguin A, Lambert J, Lacroix C, Canet E, et al. Outcomes of mechanically ventilated hematology patients with invasive pulmonary aspergillosis. Intensive Care Med. 2011;37:1605–12.CrossRefPubMed
3.
4.
Marchetti O, Bille J, Fluckiger U, Eggimann P, Ruef C, Garbino J, et al. Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991–2000. Clin Infect Dis. 2004;38:311–20.CrossRefPubMed
5.
Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302:2323–9.CrossRefPubMed
6.
Colombo AL, Guimaraes T, Sukienik T, Pasqualotto AC, Andreotti R, Queiroz-Telles F, 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;40:1489–98.CrossRefPubMedPubMedCentral
7.
Lortholary O, Renaudat C, Sitbon K, Madec Y, Denoeud-Ndam L, Wolff M, et al. Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002–2010). Intensive Care Med. 2014;40:1303–12.CrossRefPubMedPubMedCentral
8.
Kazak E, Akin H, Ener B, Sigirli D, Ozkan O, Gurcuoglu E, et al. An investigation of Candida species isolated from blood cultures during 17 years in a university hospital. Mycoses. 2014;57:623–9.CrossRefPubMed
9.
Cleveland AA, Harrison LH, Farley MM, Hollick R, Stein B, Chiller TM, et al. Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008–2013: results from population-based surveillance. PLoS One. 2015;10:e0120452.CrossRefPubMedPubMedCentral
10.
Bassetti M, Merelli M, Righi E, Diaz-Martin A, Rosello EM, Luzzati R, et al. Epidemiology, species distribution, antifungal susceptibility, and outcome of candidemia across five sites in Italy and Spain. J Clin Microbiol. 2013;51:4167–72.CrossRefPubMedPubMedCentral
11.
Leroy O, Bailly S, Gangneux JP, Mira JP, Devos P, Dupont H, et al. Systemic antifungal therapy for proven or suspected invasive candidiasis: the AmarCAND 2 study. Ann Intensive Care. 2016;6:2.CrossRefPubMedPubMedCentral
12.
Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1–50.CrossRefPubMed
13.
Klingspor L, Tortorano AM, Peman J, Willinger B, Hamal P, Sendid B, et al. Invasive Candida infections in surgical patients in intensive care units: a prospective, multicentre survey initiated by the European Confederation of Medical Mycology (ECMM) (2006–2008). Clin Microbiol Infect. 2015;21:87.e1–10.CrossRef
14.
Montagna MT, Lovero G, Borghi E, Amato G, Andreoni S, Campion L, et al. Candidemia in intensive care unit: a nationwide prospective observational survey (GISIA-3 study) and review of the European literature from 2000 through 2013. Eur Rev Med Pharmacol Sci. 2014;18:661–74.PubMed
15.
Guinea J. Global trends in the distribution of Candida species causing candidemia. Clin Microbiol Infect. 2014;20 Suppl 6:5–10.CrossRef
16.
Puig-Asensio M, Padilla B, Garnacho-Montero J, Zaragoza O, Aguado JM, Zaragoza R, et al. Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect. 2014;20:O245–54.CrossRefPubMed
17.
Arendrup MC. Update on antifungal resistance in Aspergillus and Candida. Clin Microbiol Infect. 2014;20 Suppl 6:42–8.CrossRefPubMed
18.
Morace G, Borghi E. Fungal infections in ICU patients: epidemiology and the role of diagnostics. Minerva Anestesiol. 2010;76:950–6.PubMed
19.
Schelenz S, Barnes RA, Barton RC, Cleverley JR, Lucas SB, Kibbler CC, et al. British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases. Lancet Infect Dis. 2015;15:461–74.CrossRefPubMed
20.
Clancy CJ, Nguyen MH. Finding the “missing 50 %” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013;56:1284–92.CrossRefPubMed
21.
Lamoth F, Cruciani M, Mengoli C, Castagnola E, Lortholary O, Richardson M, et al. β-Glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: a systematic review and meta-analysis of cohort studies from the Third European Conference on Infections in Leukemia (ECIL-3). Clin Infect Dis. 2012;54:633–43.CrossRefPubMed
22.
Karageorgopoulos DE, Vouloumanou EK, Ntziora F, Michalopoulos A, Rafailidis PI, Falagas ME. β-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis. 2011;52:750–70.CrossRefPubMed
23.
He S, Hang JP, Zhang L, Wang F, Zhang DC, Gong FH. A systematic review and meta-analysis of diagnostic accuracy of serum 1,3-β-D-glucan for invasive fungal infection: focus on cutoff levels. J Microbiol Immunol Infect. 2015;48:351–61.CrossRefPubMed
24.
Mikulska M, Calandra T, Sanguinetti M, Poulain D, Viscoli C. The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia. Crit Care. 2010;14:R222.CrossRefPubMedPubMedCentral
25.
26.
Neely LA, Audeh M, Phung NA, Min M, Suchocki A, Plourde D, et al. T2 magnetic resonance enables nanoparticle-mediated rapid detection of candidemia in whole blood. Sci Transl Med. 2013;5:182ra54.CrossRefPubMed
27.
Mylonakis E, Clancy CJ, Ostrosky-Zeichner L, Garey KW, Alangaden GJ, Vazquez JA, et al. T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Clin Infect Dis. 2015;60:892–9.CrossRefPubMed
28.
Bilir SP, Ferrufino CP, Pfaller MA, Munakata J. The economic impact of rapid Candida species identification by T2Candida among high-risk patients. Future Microbiol. 2015;10:1133–44.CrossRefPubMed
29.
Yang SP, Chen YY, Hsu HS, Wang FD, Chen LY, Fung CP. A risk factor analysis of healthcare-associated fungal infections in an intensive care unit: a retrospective cohort study. BMC Infect Dis. 2013;13:10.CrossRefPubMedPubMedCentral
30.
Holley A, Dulhunty J, Blot S, Lipman J, Lobo S, Dancer C, et al. Temporal trends, risk factors and outcomes in albicans and non-albicans candidaemia: an international epidemiological study in four multidisciplinary intensive care units. Int J Antimicrob Agents. 2009;33:554–7.PubMed
31.
Jorda-Marcos R, Alvarez-Lerma F, Jurado M, Palomar M, Nolla-Salas J, Leon MA, et al. Risk factors for candidaemia in critically ill patients: a prospective surveillance study. Mycoses. 2007;50:302–10.CrossRefPubMed
32.
Leon C, Ruiz-Santana S, Saavedra P, Almirante B, Nolla-Salas J, varez-Lerma F, et al. A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med. 2006;34:730–7.CrossRefPubMed
33.
Leon C, Ruiz-Santana S, Saavedra P, Galvan B, Blanco A, Castro C, et al. Usefulness of the “Candida score” for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study. Crit Care Med. 2009;37:1624–33.CrossRefPubMed
34.
Chakrabarti A, Sood P, Rudramurthy SM, Chen S, Kaur H, Capoor M, et al. Incidence, characteristics and outcome of ICU-acquired candidemia in India. Intensive Care Med. 2015;41:285–95.CrossRefPubMed
35.
Pittet D, Monod M, Suter PM, Frenk E, Auckenthaler R. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg. 1994;220:751–8.CrossRefPubMedPubMedCentral
36.
Eggimann P, Pittet D. Candida colonization index and subsequent infection in critically ill surgical patients: 20 years later. Intensive Care Med. 2014;40:1429–48.CrossRefPubMedPubMedCentral
37.
Michalopoulos AS, Geroulanos S, Mentzelopoulos SD. Determinants of candidemia and candidemia-related death in cardiothoracic ICU patients. Chest. 2003;124:2244–55.CrossRefPubMed
38.
Shorr AF, Tabak YP, Johannes RS, Sun X, Spalding J, Kollef MH. Candidemia on presentation to the hospital: development and validation of a risk score. Crit Care. 2009;13:R156.CrossRefPubMedPubMedCentral
39.
Paphitou NI, Ostrosky-Zeichner L, Rex JH. 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. 2005;43:235–43.CrossRefPubMed
40.
Ostrosky-Zeichner L, Sable C, Sobel J, Alexander BD, Donowitz G, Kan V, et al. 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. 2007;26:271–6.CrossRefPubMed
41.
Playford EG, Lipman J, Kabir M, McBryde ES, Nimmo GR, Lau A, et al. Assessment of clinical risk predictive rules for invasive candidiasis in a prospective multicentre cohort of ICU patients. Intensive Care Med. 2009;35:2141–5.CrossRefPubMed
42.
43.
Tissot F, Lamoth F, Hauser PM, Orasch C, Fluckiger U, Siegemund M, et al. β-Glucan antigenemia anticipates diagnosis of blood culture-negative intraabdominal candidiasis. Am J Respir Crit Care Med. 2013;188:1100–9.CrossRefPubMed
44.
Posteraro B, De Pascale G, Tumbarello M, Torelli R, Pennisi MA, Bello G, et al. 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. 2011;15:R249.CrossRefPubMedPubMedCentral
45.
Jaijakul S, Vazquez JA, Swanson RN, Ostrosky-Zeichner L. (1,3)-β-D-glucan as a prognostic marker of treatment response in invasive candidiasis. Clin Infect Dis. 2012;55:521–6.CrossRefPubMed
46.
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 7:19–37.CrossRefPubMed
47.
Bassetti M, Leon C, Timsit JF. Are prophylactic antifungals in highly colonized patients safe and effective? Intensive Care Med. 2015;41:1336–9.CrossRefPubMed
48.
Ferreira D, Grenouillet F, Blasco G, Samain E, Henon T, Dussaucy A, et al. Outcomes associated with routine systemic antifungal therapy in critically ill patients with Candida colonization. Intensive Care Med. 2015;41:1077–88.CrossRefPubMed
49.
Knitsch W, Vincent JL, Utzolino S, Francois B, Dinya T, Dimopoulos G, et al. A randomized, placebo-controlled trial of preemptive antifungal therapy for the prevention of invasive candidiasis following gastrointestinal surgery for intra-abdominal infections. Clin Infect Dis. 2015;61:1671–8.PubMedPubMedCentral
50.
Bassetti M, Marchetti M, Chakrabarti A, Colizza S, Garnacho-Montero J, Kett DH, et al. A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts. Intensive Care Med. 2013;39:2092–106.CrossRefPubMed
51.
Fish DN. Antifungal dosing in dialysis and continuous renal replacement therapy. Curr Fungal Infect Rep. 2011;5:75–82.CrossRef
52.
Sinnollareddy MG, Roberts JA, Lipman J, Akova M, Bassetti M, De Waele JJ, et al. Pharmacokinetic variability and exposures of fluconazole, anidulafungin, and caspofungin in intensive care unit patients: data from multinational Defining Antibiotic Levels in Intensive care unit (DALI) patients study. Crit Care. 2015;19:33.CrossRefPubMedPubMedCentral
53.
Sinnollareddy MG, Roberts MS, Lipman J, Lassig-Smith M, Starr T, Robertson T, et al. Determination of subcutaneous interstitial fluid penetration and pharmacokinetics of fluconazole in intensive care unit patients with sepsis using in vivo microdialysis. Antimicrob Agents Chemother. 2015;60:827–32.CrossRefPubMed
54.
Muilwijk EW, Schouten JA, van Leeuwen HJ, van Zanten AR, de Lange DW, Colbers A, et al. Pharmacokinetics of caspofungin in ICU patients. J Antimicrob Chemother. 2014;69:3294–9.CrossRefPubMed
55.
Grau S, Luque S, Campillo N, Samso E, Rodriguez U, Garcia-Bernedo CA, et al. Plasma and peritoneal fluid population pharmacokinetics of micafungin in post-surgical patients with severe peritonitis. J Antimicrob Chemother. 2015;70:2854–61.CrossRefPubMed
56.
Ashbee HR, Barnes RA, Johnson EM, Richardson MD, Gorton R, Hope WW. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology. J Antimicrob Chemother. 2014;69:1162–76.CrossRefPubMedPubMedCentral
57.
Park WB, Kim NH, Kim KH, Lee SH, Nam WS, Yoon SH, et al. The effect of therapeutic drug monitoring on safety and efficacy of voriconazole in invasive fungal infections: a randomized controlled trial. Clin Infect Dis. 2012;55:1080–7.CrossRefPubMed
58.
Dolton MJ, Ray JE, Marriott D, McLachlan AJ. Posaconazole exposure-response relationship: evaluating the utility of therapeutic drug monitoring. Antimicrob Agents Chemother. 2012;56:2806–13.CrossRefPubMedPubMedCentral
59.
Brosh-Nissimov T, Ben-Ami R. Differential association of fluconazole dose and dose/MIC ratio with mortality in patients with Candida albicans and non-albicans bloodstream infection. Clin Microbiol Infect. 2015;21:1011–7.CrossRefPubMed
60.
van der Elst KC, Brouwers CH, van den Heuvel ER, van Wanrooy MJ, Uges DR, van der Werf TS, et al. Subtherapeutic posaconazole exposure and treatment outcome in patients with invasive fungal disease. Ther Drug Monit. 2015;37:766–71.CrossRefPubMed
Metadata
Title
Diagnosis and management of invasive candidiasis in the ICU: an updated approach to an old enemy
Authors
Thierry Calandra
Jason A. Roberts
Massimo Antonelli
Matteo Bassetti
Jean-Louis Vincent
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2016
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-016-1313-6

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