Oral step down
Guidelines for step-down therapy No current national or international guidelines provide specific
recommendations for step-down therapy of invasive fungal disease in neutropenic patients. The ESCMID guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT)23
that fluconazole should only be considered as a stepdown treatment option in neutropenia when the Candida species isolated demonstrate susceptibility to fluconazole. An interesting overview of all of the published guidance was provided by a working group who used the AGREE (Appraisal of Guidelines Research and Evaluation) Instrument.24
Prescribing Group. Scottish Antimicrobial Prescribing Group (SAPG): development and impact of the Scottish National Antimicrobial Stewardship Programme. Int J Antimicrob Agents 2011;38(1):16–26.
3. Drew RH: Antimicrobial stewardship programs: how to start and steer a successful program. J Manag Care Pharm 2009;15:S18–S23.
4. Ananda-Rajah MR, Slavin MA, Thursky KT. The case for antifungal stewardship. Curr Opin Infect Dis 2012;25:107–15.
5. Aitken SL et al. Clinical practice patterns in hospitalized patients at risk for invasive candidiasis: role of antifungal stewardship programs in an era of rapid diagnostics. Pharmacotherapy 2014;48(6):683–90.
similarities and differences between guidelines, and provides some areas of consideration for guideline development in the future to provide a practical critique of antifungal treatment guidelines for haemato-oncologists. They concluded that step-down therapy should be considered if a patient is clinically responding to treatment for a presumed invasive fungal disease and is well enough to be changed to an oral agent.24 Other guidelines discuss the topic but make no recommendation.1,25–31
Overall there seems little in the way of guidelines or direct evidence; however, the detailed analysis undertaken by Agarwal et al25
that that step-down
therapy should be considered if a patient is clinically responding to treatment for a presumed invasive fungal disease and is well enough to be changed to an oral agent seems to be broadly in line with the evidence for non-neutropenic patients and may form the basis for decision making for physicians dealing with the complex group of patients and suggest that future guidelines should address this issue more fully. l
References 1. Society for Healthcare Epidemiology of America (SHEA), Infectious Diseases Society of America (IDSA), Pediatric Infectious Diseases Society (PIDS). Policy statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS). Infect Control Hosp Epidemiol 2012;33:322–7.
2. Nathwani D et al; Scottish Antimicrobial
6. Reed EE et al. Improving the management of candidemia through antimicrobial stewardship interventions. Diagn Microbiol Infect Dis 2014;78(2):157–61.
7. Vermeulen E, Lagrou K, Verweij PE. Azole resistance in Aspergillus fumigatus: a growing public health concern. Curr Opin Infect Dis 2013;26(6):493–500.
8. Ruhnke M. Antifungal stewardship in invasive Candida infections. Clin Microbiol Infect 2014;20 Suppl 6:11–18.
9. Pappas PG et al; Infectious Diseases Society of America. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009;48:503–35.
10. 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.
11. Vazquez J. Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: results from an open-label trial. BMC Infect Dis 2014;14:97.
12. Kullberg BJ et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in nonneutropenic patients: a randomised non-inferiority trial. Lancet 2005; 366:1435–42.
13. Pappas PG et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis 2007;45:883–93.
14. Reboli AC et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 2007;356:2472–82.
15. Schelenz S et al. Standards of care for patients with invasive fungal infections within the United Kingdom: a national audit. J Infect 2009;58:145–53.
16. Driscoll T et al. Comparison of pharmacokinetics and safety of voriconazole intravenous-to-oral switch in immunocompromised adolescents and healthy adults Antimicrob Agents Chemother 2011;55:5780–9.
17. Bergman SJ, Tyagi I, Ronald K. Antifungal dosing
in critically ill patients. Curr Fungal Infect Rep 2010;4(2):78–86.
18. Jacinto PL. Safety of posaconazole. Expert Opin Drug Saf. 2013;12(2):265–74.
19. Lestner JM Antifungal agents and therapy for infants and children with invasive fungal infections: a pharmacological perspective. Br J Clin Pharmacol. 2013;75(6):1381–95.
20. Hicks JK. Voriconazole plasma concentrations in immunocompromised pediatric patients vary by CYP2C19 diplotypes. Pharmacogenomics 2014;15(8):1065–78.
21. Pieper S. Monitoring of voriconazole plasma concentrations in immunocompromised paediatric patients. J Antimicrob Chemother. 2012;67(11):2717–24.
22. Andes D. Optimizing antifungal choice and administration. Curr Med Res Opin. 2013;29 Suppl 4:13–18.
23. Ullmann A et al; ESCMID Fungal Infection Study Group. [ESCMID* guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect. 2012;18 Suppl 7:53–67]
(accessed 26 August 2014). 25. Agarwal A. practical critique of antifungal treatment guidelines for haemato-oncologists. Crit Rev Microbiol 2012;38(3):203–16.
26. Walsh TJ et al; Infectious Diseases Society of America. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008;46:327–60.
27. Cornely OA et al. Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Haematologica 2009;94:113–22.
28. Böhme A et al; Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Treatment of invasive fungal infections in cancer patients– recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 2009;88:97–110.
29. Slavin MA. Introduction to the updated Australian and New Zealand consensus guidelines for the use of antifungal agents in the haematology/ oncology setting, 2008. Intern Med J 2008;38:457–67.
30. Prentice AG et al. Guidelines on the management of invasive fungal infection during therapy for haematological malignancy. 2008. London, UK, British Committee for Standards in Haematology;2008.
31. Maertens J et al. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3-2009 Update. Bone Marrow Transplant 2011;46(5):709–18.
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