Invasive fungal infections (IFI) in critically ill patients increase mortality. Despite this, issues regarding isolation of pathogens (lack of sensibility or diagnostic value of cultures, time-lapse required for results) imply some difficulties in the diagnosis.
Many risk factors are associated with IFI development. Clinical scores (Candida score, Nebraska Medical Center score) and biomarkers (beta-d-glucan) can help in the identification of these infections.
Given the fact that time and type of therapy are crucial to improve survival, it must be considered that critical illness often underlies conditions that significantly alter drugs’ pharmacokinetic/pharmacodynamic profile: hepatic or renal failure may affect drugs’ metabolism and elimination, and the frequent administration of multiple therapies to the patient increases the risk of pharmacological interactions. This makes antifungal’s plasmatic level variable and hardly predictable, conditioning both therapeutic effect and toxicity.
The main antifungals available for critical settings are echinocandins (caspofungin, micafungin, anidulafungin), azoles (fluconazole, voriconazole), and amphotericin B: their spectra of action, indications, and conditions that require dose adjustments are analyzed separately. A more “pharmacological view,” which takes into account variation in volume of distribution (Vd) of drugs in such settings, is likely to be necessary when managing critically ill patients with IFI, but a relatively poor state of knowledge has highlighted the need of more evidences in the pharmacology of antifungal drugs.
Invasive fungal infections Echinocandins Azoles Amphotericin B Pharmacokinetics/pharmacodynamics
This is a preview of subscription content, log in to check access.
Schmiedel Y, Zimmerli S. Common invasive fungal diseases: an overview of invasive candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia. Swiss Med Wkly. 2016;146:1–12.Google Scholar
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.CrossRefGoogle Scholar
Pappas PG, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2015;62:e1–e50.PubMedPubMedCentralGoogle Scholar
Garey KW, 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.CrossRefGoogle Scholar
Tissot F, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017;102:433–44.CrossRefGoogle Scholar
Eggimann P, Garbino J, Pittet D. Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis. 2003;3:685–702.CrossRefGoogle Scholar
Yang S-P, et al. A risk factor analysis of healthcare-associated fungal infections in an intensive care unit: a retrospective cohort study. BMC Infect Dis. 2013;13:10.CrossRefGoogle Scholar
Bassetti M, Mikulska M, Viscoli C. Bench-to-bedside review: therapeutic management of invasive candidiasis in the intensive care unit. Crit Care. 2010;14:244.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Glöckner a, Karthaus M. Current aspects of invasive candidiasis and aspergillosis in adult intensive care patients. Mycoses. 2011;54:420–33.CrossRefGoogle Scholar
León C, 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.CrossRefGoogle Scholar
León 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.CrossRefGoogle Scholar
Hermsen ED, et al. Validation and comparison of clinical prediction rules for invasive candidiasis in intensive care unit patients: a matched case-control study. Crit Care. 2011;15:R198.CrossRefGoogle Scholar
Garnacho-Montero J, et al. Epidemiology, diagnosis and treatment of fungal respiratory infections in the critically ill patient. Rev Esp Quimioter. 2013;26:173–88.PubMedGoogle Scholar
Gow NAR, Veerdonk FLVD, Brown AJP, Netea MG. Europe PMC Funders Group. Candida albicans morphogenesis and host defence : discriminating invasion from colonization. Nat Rev Microbiol. 2013;10:112–22.CrossRefGoogle Scholar
Miyazaki T, et al. Plasma (1-->3)-beta-D-glucan and fungal antigenemia in patients with candidemia, aspergillosis, and cryptococcosis. J Clin Microbiol. 1995;33:3115–8.PubMedPubMedCentralGoogle Scholar
Odabasi Z, et al. Differences in beta-glucan levels in culture supernatants of a variety of fungi. Med Mycol. 2006;44:267–72.CrossRefGoogle Scholar
Blot SI, Pea F, Lipman J. The effect of pathophysiology on pharmacokinetics in the critically ill patient - concepts appraised by the example of antimicrobial agents. Adv Drug Deliv Rev. 2014;77:3–11.CrossRefGoogle Scholar
Katzung BG, Masters SB, Trevor AJ. Basic and clinical pharmacology. London: McGraw-Hill Education; 2014.Google Scholar
Pea F. Plasma pharmacokinetics of antimicrobial agents in critically ill patients. Curr Clin Pharmacol. 2013;8:5–12.PubMedGoogle Scholar
Sinnollareddy MG, 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.CrossRefGoogle Scholar
Pea F. Current pharmacological concepts for wise use of echinocandins in the treatment of Candida infections in septic critically ill patients. Expert Rev Anti Infect Ther. 2013;11:989–97.CrossRefGoogle Scholar
Scott LJ. Voriconazole: a review of its use in the management of invasive fungal infections. Drugs. 2007;67:269–98.CrossRefGoogle Scholar
McCormack P, Perry C. Caspofungin: a review of its use in the treatment of fungal infections. Drugs. 2005;65:2049–68.CrossRefGoogle Scholar
Oude Lashof AML, et al. Safety and tolerability of voriconazole in patients with baseline renal insufficiency and candidemia. Antimicrob Agents Chemother. 2012;56:3133–7.CrossRefGoogle Scholar
Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy. 2009;29:562–77.CrossRefGoogle Scholar
Ashbee HR, et al. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the british society for medical mycology. J Antimicrob Chemother. 2014;69:1162–76.CrossRefGoogle Scholar
Calandra T, et al. Diagnosis and management of invasive candidiasis in the ICU: an updated approach to an old enemy. Crit Care. 2016;20:125.CrossRefGoogle Scholar
Cornely OA, 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.CrossRefGoogle Scholar
Dimopoulos G, Antonopoulou A, Armaganidis A, Vincent J-L. How to select an antifungal agent in critically ill patients. J Crit Care. 2013;28:717–27.CrossRefGoogle Scholar
Cancidas. Prescribing information-(caspofungin acetate) for injection.Google Scholar
Chen SC, et al. Consensus guidelines for the treatment of yeast infections in the haematology, oncology and intensive care setting, 2014. Intern Med J. 2014;44:1315–32.CrossRefGoogle Scholar
O Marchetti, F Lamoth, M Mikulska, C Viscoli, P Verweij, S Bretagne, (2012) ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients. Bone Marrow Transplantation 47 (6):846-854.CrossRefGoogle Scholar