Invasive Fungal Infections in the Intensive Care Unit

ABSTRACT

Invasive fungal infections, especially candidemia and systemic candidiasis, have become a major cause of morbidity and mortality in the last few decades. This comes in parallel with the major advances made in intensive care. Patients who are critically ill, in medical or surgical ICUs are especially at risk for Candida infections. Invasive candidiasis accounts for up to 15 to 30% of all nosocomial infections in critically ill patients. Management of these severe infections has been challenging due to a lack of rapid and reliable diagnostic methods, leading to delays in initiating appropriate antifungal therapy. However, some notable improvements have been made in diagnostics with improved culturing methods, rapid species identification, and detection of fungemia with newer antigen assays. Newer classes of antifungals have recently become available with broader antifungal activity, fewer drug–drug interactions, and improved tolerability when compared with the older antifungal agents. Despite these advancements, the mortality rates associated with candidiasis remain excessively high, with an overall mortality in the range of 30 to 50% and an attributable mortality of ~30%. In addition to this high case-fatality rate, candidemia is also associated with a substantial economic burden, primarily due to an extended length of stay. Strategies to evaluate either the prevention, early diagnosis, or initiation of appropriate therapy should yield both clinical and socioeconomic benefits.

KEYWORDS

Candidiasis - antifungals - ICU - systemic fungal infections - outcomes

REFERENCES

• 1 Martin G S, Mannino D M, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000.  N Engl J Med. 2003;  348 1546-1554
• 2 Vazquez J A, Sobel J D. Candidiasis. In: Dismukes WE, Pappas PG, Sobel JD Clinical Mycology. London; Oxford University Press 2003: 143-187
• 3 Pfaller M A, Diekema D J. Epidemiology of invasive candidiasis: a persistent public health problem.  Clin Microbiol Rev. 2007;  20 133-163
• 4 Pappas P G. Invasive candidiasis.  Infect Dis Clin North Am. 2006;  20 485-506
• 5 Horn D L, Neofytos D, Anaissie E J et al.. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry.  Clin Infect Dis. 2009;  48 1695-1703
• 6 Pappas P G, Rex J H, Lee J NIAID Mycoses Study Group et al. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients.  Clin Infect Dis. 2003;  37 634-643
• 7 Morgan J. Global trends in candidemia: review of reports from 1995–2005.  Curr Infect Dis Rep. 2005;  7 429-439
• 8 Colombo A L, Nucci M, Park B J Brazilian Network Candidemia Study et al. Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers.  J Clin Microbiol. 2006;  44 2816-2823
• 9 Eiland E H, Hassoun A, English T. Points of concern related to the micafungin versus caspofungin trial.  Clin Infect Dis. 2008;  46 640-641, author reply 641
• 10 Yang Y L. Virulence factors of Candida species.  J Microbiol Immunol Infect. 2003;  36 223-228
• 11 Wey S B, Mori M, Pfaller M A, Woolson R F, Wenzel R P. Hospital-acquired candidemia: the attributable mortality and excess length of stay.  Arch Intern Med. 1988;  148 2642-2645
• 12 Menzin J M, Meyers J L, Friedman M et al.. Mortality, length of hospitalization, and costs associated with invasive fungal infections in high-risk patients.  Am J Health Syst Pharm. 2009;  66 1711-1717
• 13 Rentz A M, Halpern M T, Bowden R. The impact of candidemia on length of hospital stay, outcome, and overall cost of illness.  Clin Infect Dis. 1998;  27 781-788
• 14 Shah C P, McKey J, Spirn M J, Maguire J. Ocular candidiasis: a review.  Br J Ophthalmol. 2008;  92 466-468
• 15 Morrell M, Fraser V J, Kollef M H. 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. 2005;  49 3640-3645
• 16 Alexander B D, Pfaller M A. Contemporary tools for the diagnosis and management of invasive mycoses.  Clin Infect Dis. 2006;  43 S15-S27
• 17 Shepard J R, Addison R M, Alexander B D et al.. Multicenter evaluation of the Candida albicans/Candida glabrata peptide nucleic acid fluorescent in situ hybridization method for simultaneous dual-color identification of C. albicans and C. glabrata directly from blood culture bottles.  J Clin Microbiol. 2008;  46 50-55
• 18 Odabasi Z, Mattiuzzi G, Estey E et al.. Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome.  Clin Infect Dis. 2004;  39 199-205
• 19 Pappas P G, Kauffman C A, Andes D Infectious Diseases Society of America et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America.  Clin Infect Dis. 2009;  48 503-535
• 20 Kauffman C A. Clinical efficacy of new antifungal agents.  Curr Opin Microbiol. 2006;  9 483-488
• 21 Sable C A, Strohmaier K M, Chodakewitz J A. Advances in antifungal therapy.  Annu Rev Med. 2008;  59 361-379
• 22 Chandrasekar P H, Sobel J D. Micafungin: a new echinocandin.  Clin Infect Dis. 2006;  42 1171-1178
• 23 Sobel J D, Revankar S G. Echinocandins—first-choice or first-line therapy for invasive candidiasis?.  N Engl J Med. 2007;  356 2525-2526
• 24 Kuse E R, Chetchotisakd P, da Cunha C A Micafungin Invasive Candidiasis Working Group et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial.  Lancet. 2007;  369 1519-1527
• 25 Reboli A C, Rotstein C, Pappas P G Anidulafungin Study Group et al. Anidulafungin versus fluconazole for invasive candidiasis.  N Engl J Med. 2007;  356 2472-2482
• 26 Cornely O A, Lasso M, Betts R et al.. Caspofungin for the treatment of less common forms of invasive candidiasis.  J Antimicrob Chemother. 2007;  60 363-369
• 27 Kullberg B J, Sobel J D, Ruhnke M et al.. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial.  Lancet. 2005;  366 1435-1442
• 28 Viscoli C, Girmenia C, Marinus A et al.. 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. 1999;  28 1071-1079
• 29 Khan F A, Slain D, Khakoo R A. Candida endophthalmitis: focus on current and future antifungal treatment options.  Pharmacotherapy. 2007;  27 1711-1721
• 30 Charlier C, Hart E, Lefort A et al.. Fluconazole for the management of invasive candidiasis: where do we stand after 15 years?.  J Antimicrob Chemother. 2006;  57 384-410
• 31 Labelle A J, Micek S T, Roubinian N, Kollef M H. Treatment-related risk factors for hospital mortality in Candida bloodstream infections.  Crit Care Med. 2008;  36 2967-2972
• 32 Husain S, Paterson D L, Studer S et al.. Voriconazole prophylaxis in lung transplant recipients.  Am J Transplant. 2006;  6 3008-3016
• 33 Ullmann A J, Cornely O A. Antifungal prophylaxis for invasive mycoses in high risk patients.  Curr Opin Infect Dis. 2006;  19 571-576
• 34 van Burik J A, Ratanatharathorn V, Stepan D E National Institute of Allergy and Infectious Diseases Mycoses Study Group et al. Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation.  Clin Infect Dis. 2004;  39 1407-1416
• 35 Leleu G, Aegerter P, Guidet B. Collège des Utilisateurs de Base de Données en Réanimation . Systemic candidiasis in intensive care units: a multicenter, matched-cohort study.  J Crit Care. 2002;  17 168-175
• 36 Garey K W, Rege M, Pai M P et al.. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study.  Clin Infect Dis. 2006;  43 25-31
• 37 Meersseman W, Vandecasteele S J, Wilmer A, Verbeken E, Peetermans W E, Van Wijngaerden E. Invasive aspergillosis in critically ill patients without malignancy.  Am J Respir Crit Care Med. 2004;  170 621-625
• 38 Meersseman W, Lagrou K, Maertens J, Van Wijngaerden E. Invasive aspergillosis in the intensive care unit.  Clin Infect Dis. 2007;  45 205-216