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Systemic Antifungals

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Infection Control in the Intensive Care Unit

Abstract

Since approximately 2005, there have been important developments in antifungal therapy relevant to managing invasive fungal infections in the intensive care unit (ICU). There has been much debate on how best to use systemic antifungals in this setting, with the focus on prophylaxis, empirical, pre-emptive and definitive therapy. New agents have been added to the armamentarium and are concentrated on in this chapter. These agents include posaconazole, a new triazole; and two newer echinocandins, anidulafungin and micafungin. Here, their licensed clinical indications, spectra of activity, pharmacological properties and the experience of their use to date are reviewed. Other issues discussed include the role of combination antifungal therapy, antifungal susceptibility testing, the impact of the changing epidemiology of invasive mycoses in intensive care, the relationship between treating invasive candidiasis/candidaemia and outcome, as well as approaches to antifungal therapy in the ICU.

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References

  1. Cooke FJ, Rogers T (2005) Systemic antifungals. In: van Saene HKF, Silvestri L, de la Cal MA (eds) Infection control in the intensive care unit, 2nd edn. Springer, Berlin, pp 155–170

    Chapter  Google Scholar 

  2. Schiller DS, Fung HB (2007) Posaconazole: an extended-spectrum triazole antifungal agent. Clin Ther 29:1862–1886

    Article  PubMed  CAS  Google Scholar 

  3. Ullmann AJ, Lipton JH, Vesole DH et al (2007) Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 356:335–347

    Article  PubMed  CAS  Google Scholar 

  4. Cornely OA, Maertens J, Winston DJ et al (2007) Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 356:348–359

    Article  PubMed  CAS  Google Scholar 

  5. Walsh TJ, Anaissie EJ, Denning DW et al (2008) Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 46:327–360

    Article  PubMed  CAS  Google Scholar 

  6. Walsh TJ, Raad I, Patterson TF et al (2007) Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis 44:2–12

    Article  PubMed  CAS  Google Scholar 

  7. Greenberg RN, Mullane K, van Burik JA et al (2006) Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother 50:126–133

    Article  PubMed  CAS  Google Scholar 

  8. van Burik JA, Hare RS, Solomon HF et al (2006) Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin Infect Dis 42:e61–e65

    Article  PubMed  Google Scholar 

  9. Page RL 2nd, Schwiesow J, Hilts A (2007) Posaconazole as salvage therapy in a patient with disseminated zygomycosis: case report and review of the literature. Pharmacotherapy 27:290–298

    Article  PubMed  Google Scholar 

  10. Zoller E, Valente C, Klepser ME (2010) Development, clinical utility, and place in therapy of posaconazole for prevention and treatment of invasive fungal infections. Drug Des Devel Ther 4:299–311

    PubMed  CAS  Google Scholar 

  11. Strorzinger D, Lichtenstern C, Weigand MA et al (2011) Posaconazole as part of the antifungal armamentarium in the intensive care unit-case reports from a surgical ICU. Mycoses 54(suppl 1):45–48

    Article  Google Scholar 

  12. Shields RK, Clancy CJ, Vadnerkar A et al (2010) Posaconazole serum concentrations among cardiothoracic transplant recipients: factors impacting levels and correlation with clinical response. Antimicrob Agents Chemother 55(3):1308–1311

    Article  PubMed  Google Scholar 

  13. Pappas PG, Kauffman CA, Andes D et al (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48:503–535

    Article  PubMed  CAS  Google Scholar 

  14. Pappas PG, Rotstein CM, Betts RF et al (2007) Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis 45:883–893

    Article  PubMed  CAS  Google Scholar 

  15. Vazquez JA (2010) Invasive fungal infections in the intensive care unit. Semin Respir Crit Care Med 31:79–86

    Article  PubMed  Google Scholar 

  16. Wagner C, Graninger W, Presterl E et al (2006) The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications. Pharmacology 78:161–177

    Article  PubMed  CAS  Google Scholar 

  17. Betts RF, Nucci M, Talwar D et al (2009) A multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis 48:1676–1684

    Article  PubMed  CAS  Google Scholar 

  18. Kuse ER, Chetchotisakd P, da Cunha CA et al (2007) Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 369:1519–1527

    Article  PubMed  CAS  Google Scholar 

  19. Pappas PG, Rotstein CM, Betts RF et al (2007) Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis 45:883–893

    Article  PubMed  CAS  Google Scholar 

  20. Dupont BF, Lortholary O, Ostrosky-Zeichner L et al (2009) Treatment of candidemia and invasive candidiasis in the intensive care unit: post hoc analysis of a randomized, controlled trial comparing micafungin and liposomal amphotericin B. Crit Care 13:R159

    Article  PubMed  Google Scholar 

  21. Queiroz-Telles F, Berezin E, Leverger G et al (2008) Micafungin versus liposomal amphotericin B for pediatric patients with invasive candidiasis. Pediatr Infect Dis 27:820–826

    Article  Google Scholar 

  22. de Wet N, Llanos-Cuentas A, Suleiman J et al (2004) A randomized, double-blind, parallel-group, dose-response study of micafungin compared with fluconazole for the treatment of esophageal candidiasis in HIV-positive patients. Clin Infect Dis 39:842–849

    Article  PubMed  Google Scholar 

  23. de Wet NT, Bester AJ, Viljoen JJ et al (2005) A randomized, double blind, comparative trial of micafungin (FK463) vs. fluconazole for the treatment of oesophageal candidiasis. Aliment Pharmacol Ther 21:899–907

    Article  PubMed  Google Scholar 

  24. van Burik JA, Ratanatharathorn V, Stepan DE et al (2004) Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis 39:1407–1416

    Article  PubMed  Google Scholar 

  25. Denning DW, Marr KA, Lau WM et al (2006) Micafungin (FK463), alone or in combination with other systemic antifungal agents, for the treatment of acute invasive aspergillosis. J Infect 53:337–349

    Article  PubMed  Google Scholar 

  26. Perkhofer S, Lass-Florl C (2009) Anidulafungin and voriconazole in invasive fungal disease: pharmacological data and their use in combination. Expert Opin Investig Drugs 18:1393–1404

    Article  PubMed  CAS  Google Scholar 

  27. Reboli AC, Rotstein C, Pappas PG et al (2007) Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 356:2472–2482

    Article  PubMed  CAS  Google Scholar 

  28. Krause DS, Simjee AE, van Rensburg C et al (2004) A randomized, double-blind trial of anidulafungin versus fluconazole for the treatment of esophageal candidiasis. Clin Infect Dis 39:770–775

    Article  PubMed  CAS  Google Scholar 

  29. Kauffman CA, Bustamante B, Chapman SW et al (2007) Clinical practice guidelines for the management of sporotrichosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis 45:1255–1265

    Article  PubMed  CAS  Google Scholar 

  30. Perfect JR, Dismukes WE, Dromer F et al (2010) Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 50:291–322

    Article  PubMed  Google Scholar 

  31. Chapman SW, Dismukes WE, Proia LA et al (2008) Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis 46:1801–1812

    Article  PubMed  CAS  Google Scholar 

  32. Galgiani JN, Ampel NM, Blair JE et al (2005) Coccidioidomycosis. Clin Infect Dis 41:1217–1223

    Article  PubMed  Google Scholar 

  33. Wheat LJ, Freifeld AG, Kleiman MB et al (2007) Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis 45:807–825

    Article  PubMed  Google Scholar 

  34. Cuenca-Estrella M, Rodriguez-Tudela JL (2010) The current role of the reference procedures by CLSI and EUCAST in the detection of resistance to antifungal agents in vitro. Expert Rev Anti Infect Ther 8:267–276

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  36. Kett DH, Azoulay E, Echeverria PM et al. for the Extended Prevalence of Infection in the ICU Study (EPIC. II) Group of investigators (2010) Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in an intensive care unit study. Crit Care Med 39(4):665-670

    Google Scholar 

  37. Lass-Florl C (2009) The changing face of epidemiology of invasive fungal disease in Europe. Mycoses 52:197–205

    Article  PubMed  Google Scholar 

  38. Bassetti M, Ansaldi F, Nicolini L et al (2009) Incidence of candidaemia and relationship with fluconazole use in an intensive care unit. J Antimicrob Chemother 64:625–629

    Article  PubMed  CAS  Google Scholar 

  39. Pfaller MA, Moet GJ, Messer SA et al (2010) Candida bloodstream infections: comparison of species distribution and antifungal resistance in community onset and nosocomial isolates in the SENTRY antimicrobial surveillance program (2008–2009). Antimicrob Agents Chemother 55(2):561–566

    Article  PubMed  Google Scholar 

  40. Parkins MD, Sabuda DM, Elsayed S et al (2007) Adequacy of empirical antifungal therapy and effect on outcome among patients with invasive Candida species infections. J Antimicrob Chemother 60:613–618

    Article  PubMed  CAS  Google Scholar 

  41. Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodovar A et al (2003) Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit Care Med 31:2742–2751

    Article  PubMed  Google Scholar 

  42. 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 49:3640–3645

    Article  PubMed  CAS  Google Scholar 

  43. Cruciani M, Serpelloni G (2008) Management of Candida infections in the adult intensive care unit. Expert Opin Pharmacother 9:175–191

    Article  PubMed  CAS  Google Scholar 

  44. Clerihew L, Austin N, McGuire W (2007) Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants. Cochrane Database Syst Rev (4):CD003850

    Google Scholar 

  45. Guery BP, Arendrup MC, Auzinger G et al (2009) Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients. Part II: Treatment. Intensive Care Med 35:206–214

    Article  PubMed  CAS  Google Scholar 

  46. Troughton JA, Browne G, McAuley DF et al (2010) Prior colonisation with Candida species fails to guide empirical therapy for candidaemia in critically ill adults. J Infect 61:403–409

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  48. Rex JH, Bennett JE, Sugar AM et al (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 

  49. Zilberberg MD, Kothan S, Shorr AF (2009) Cost-effectiveness of micafungin as an alternative to fluconazole empiric treatment of suspected ICU-acquired candidemia among patients with sepsis: a model simulation. Crit Care 13:R94

    Article  PubMed  Google Scholar 

  50. Golan Y, Wolf MP, Pauker SG et al (2005) Empirical anti-Candida therapy among selected patients in the intensive care unit: a cost effectiveness analysis. Ann Intern Med 143:857–869

    PubMed  Google Scholar 

  51. Golan Y (2009) Empiric anti-Candida therapy for patients with sepsis in the ICU: how little is too little? Crit Care 13:180

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Clinical Microbiology, Trinity College Dublin, Dublin, Leinster, Republic of Ireland

    C. J. Collins

  2. Clinical Microbiology, St. James’s Hospital and Trinity College Dublin, Sir Patrick Dun Laboratory, St. James’s Hospital, Dublin, Leinster, 8, Republic of Ireland

    Th. R. Rogers

Authors
  1. C. J. Collins
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  2. Th. R. Rogers
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Corresponding author

Correspondence to C. J. Collins .

Editor information

Editors and Affiliations

  1. , Institute of Aging and Chronic Diseases, University Liverpool, Daulby Street, Liverpool, L69 3GA, United Kingdom

    Hendrick K.F. van Saene

  2. , Dept. Emergency, Hospital Gorizia, Via Vittorio Veneto 171, Gorizia, 34170, Italy

    Luciano Silvestri

  3. , Department of Intensive Care Medicine, Hospital Universitario de Getafe, Carretera de Toledo km 12.5, Getafe, 28045, Spain

    Miguel A. de la Cal

  4. Policlinico di Catania, UCO di Anestesia e Rianimazione, Azienda Ospedaliero-Universitaria, Via Santa Sofia 78, Catania, 95100, Italy

    Antonino Gullo

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Collins, C.J., Rogers, T.R. (2011). Systemic Antifungals. In: van Saene, H., Silvestri, L., de la Cal, M., Gullo, A. (eds) Infection Control in the Intensive Care Unit. Springer, Milano. https://doi.org/10.1007/978-88-470-1601-9_7

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  • DOI: https://doi.org/10.1007/978-88-470-1601-9_7

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  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-1600-2

  • Online ISBN: 978-88-470-1601-9

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