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Antifungal Stewardship: an Emerging Practice in Antimicrobial Stewardship

  • Mycology (J Perfect, Section Editor)
  • Published:
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Abstract

Antimicrobial stewardship programs have gained increasing popularity in hospitals worldwide, given the growing emphasis on reducing antimicrobial resistance and data demonstrating inappropriate antibacterial drug use. Data on overuse and opportunities to optimize antifungal drug therapy justify that similar efforts should be focused on antifungal stewardship. Although more limited than antibacterial stewardship efforts, data are emerging that provide focus for antifungal stewardship activities. In this review, we discuss the essential elements for antifungal stewardship and compare and contrast with core elements for overall antimicrobial stewardship, highlighting areas where unique aspects of antifungal therapy provide opportunities for distinct stewardship strategies. A review of available data on successful antifungal stewardship activities provides examples of successful antifungal stewardship interventions that can be implemented in the acute care setting.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Dellit TH et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44(2):159–77.

    Article  PubMed  Google Scholar 

  2. Magill SS et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370(13):1198–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Valerio M et al. Evaluation of antifungal use in a tertiary care institution: antifungal stewardship urgently needed. J Antimicrob Chemother. 2014;69(7):1993–9. This article makes a compelling case for antifungal stewardship and will be a great tool for trying to justify the need to administrators.

    Article  CAS  PubMed  Google Scholar 

  4. CDC, Core Elements of Hospital Antibiotic Stewardship Programs. 2014, US Department of Health and Human Services, CDC: Atlanta.

  5. Munoz P et al. Antifungal stewardship in daily practice and health economic implications. Mycoses. 2015;58 Suppl 2:14–25. This is a comprehensive review of antifungal stewardship efforts and also lays out the essential elements for antifungal stewardship.

    Article  PubMed  Google Scholar 

  6. Polk RE et al. Measurement of adult antibacterial drug use in 130 US hospitals: comparison of defined daily dose and days of therapy. Clin Infect Dis. 2007;44(5):664–70.

    Article  CAS  PubMed  Google Scholar 

  7. Pappas PG et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1–50.

    Article  PubMed  Google Scholar 

  8. Diekema D et al. The changing epidemiology of healthcare-associated candidemia over three decades. Diagn Microbiol Infect Dis. 2012;73(1):45–8.

    Article  PubMed  Google Scholar 

  9. Alexander BD et al. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis. 2013;56(12):1724–32.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Shah DN et al. Evaluation of antifungal therapy in patients with candidaemia based on susceptibility testing results: implications for antimicrobial stewardship programmes. J Antimicrob Chemother. 2011;66(9):2146–51.

    Article  CAS  PubMed  Google Scholar 

  11. Pappas PG et al. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis. 2010;50(8):1101–11.

    Article  PubMed  Google Scholar 

  12. Kontoyiannis DP et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) database. Clin Infect Dis. 2010;50(8):1091–100.

    Article  PubMed  Google Scholar 

  13. Theuretzbacher U. Pharmacokinetic and pharmacodynamic issues for antimicrobial therapy in patients with cancer. Clin Infect Dis. 2012;54(12):1785–92.

    Article  PubMed  Google Scholar 

  14. Alfandari S, Berthon C, Coiteux V. Antifungal stewardship: implementation in a French teaching hospital. Med Mal Infect. 2014;44(4):154–8.

    Article  CAS  PubMed  Google Scholar 

  15. Kollef MH, Paiva J-A, Charles P-E. Candidemia and non-candidemia related septic shock: are there differences between them? Intensive Care Med. 2014;40(7):1046–8.

    Article  PubMed  Google Scholar 

  16. Lamagni TL et al. Emerging trends in the epidemiology of invasive mycoses in England and Wales (1990-9). Epidemiol Infect. 2001;126(3):397–414.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wisplinghoff H et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004;39(3):309–17.

    Article  PubMed  Google Scholar 

  18. Morrell M, Fraser VJ, Kollef MH. 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(9):3640–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 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(1):25–31.

    Article  CAS  PubMed  Google Scholar 

  20. Labelle AJ et al. Treatment-related risk factors for hospital mortality in Candida bloodstream infections. Crit Care Med. 2008;36(11):2967–72.

    Article  PubMed  Google Scholar 

  21. Bassetti M et al. A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med. 2014;40(6):839–45.

    Article  CAS  PubMed  Google Scholar 

  22. Leon 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(3):730–7.

    Article  PubMed  Google Scholar 

  23. Harrison D et al. Development and validation of a risk model for identification of non-neutropenic, critically ill adult patients at high risk of invasive Candida infection: the Fungal Infection Risk Evaluation (FIRE) study. Health Technol Assess. 2013;17(3):1–156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ostrosky-Zeichner L 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(4):271–6.

    Article  CAS  PubMed  Google Scholar 

  25. Leon 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(5):1624–33.

    Article  PubMed  Google Scholar 

  26. Leroy G et al. Evaluation of “Candida score” in critically ill patients: a prospective, multicenter, observational, cohort study. Ann Intensive Care. 2011;1(1):50.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ostrosky-Zeichner L et al. MSG-01: a randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting. Clin Infect Dis. 2014;58(9):1219–26.

    Article  CAS  PubMed  Google Scholar 

  28. Schuster MG et al. Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial. Ann Intern Med. 2008;149(2):83–90.

    Article  PubMed  Google Scholar 

  29. Pelz, R.K., et al., Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients. Ann Surg. 2001. 233.

  30. 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(3):235–43.

    Article  PubMed  Google Scholar 

  31. Ho KM et al. The use of prophylactic fluconazole in immunocompetent high-risk surgical patients: a meta-analysis. Crit Care. 2005;9(6):R710–7.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Vardakas KZ et al. Antifungal prophylaxis with azoles in high-risk, surgical intensive care unit patients: a meta-analysis of randomized, placebo-controlled trials. Crit Care Med. 2006;34(4):1216–24.

    Article  CAS  PubMed  Google Scholar 

  33. Zilberberg M et al. Relationship of fluconazole prophylaxis with fungal microbiology in hospitalized intra-abdominal surgery patients: a descriptive cohort study. Crit Care. 2014;18(5):1–8.

    Article  Google Scholar 

  34. Knitsch W 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(11):1671–8.

    PubMed  PubMed Central  Google Scholar 

  35. De Pauw B et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46(12):1813–21.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Maertens J et al. Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients. J Infect Dis. 2002;186(9):1297–306.

    Article  CAS  PubMed  Google Scholar 

  37. Herbrecht R et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408–15.

    Article  CAS  PubMed  Google Scholar 

  38. Walsh TJ et al. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis. 2007;44(1):2–12.

    Article  CAS  PubMed  Google Scholar 

  39. Seyedmousavi S et al. In vitro interaction of voriconazole and anidulafungin against triazole-resistant Aspergillus fumigatus. Antimicrob Agents Chemother. 2013;57(2):796–803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Seyedmousavi S et al. Efficacy and pharmacodynamics of voriconazole combined with anidulafungin in azole-resistant invasive aspergillosis. J Antimicrob Chemother. 2013;68(2):385–93.

    Article  CAS  PubMed  Google Scholar 

  41. Lepak AJ et al. Impact of in vivo triazole and echinocandin combination therapy for invasive pulmonary aspergillosis: enhanced efficacy against Cyp51 mutant isolates. Antimicrob Agents Chemother. 2013;57(11):5438–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Arvanitis M et al. Molecular and nonmolecular diagnostic methods for invasive fungal infections. Clin Microbiol Rev. 2014;27(3):490–526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. 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(9):1284–92.

    Article  PubMed  Google Scholar 

  44. Park BR et al. Comparative analysis of simulated candidemia using two different blood culture systems and the rapid identification of Candida albicans. Ann Clin Lab Sci. 2011;41(3):251–6.

    PubMed  Google Scholar 

  45. Singhal N et al. MALDI-TOF mass spectrometry: an emerging technology for microbial identification and diagnosis. Front Microbiol. 2015;6:791.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Huang AM et al. Impact of rapid organism identification via matrix-assisted laser desorption/ionization time-of-flight combined with antimicrobial stewardship team intervention in adult patients with bacteremia and candidemia. Clin Infect Dis. 2013;57(9):1237–45.

    Article  CAS  PubMed  Google Scholar 

  47. Banerjee R et al. Randomized trial of rapid multiplex polymerase chain reaction-based blood culture identification and susceptibility testing. Clin Infect Dis. 2015;61(7):1071–80.

    Article  PubMed  Google Scholar 

  48. Wilson DA et al. Multicenter evaluation of a Candida albicans peptide nucleic acid fluorescent in situ hybridization probe for characterization of yeast isolates from blood cultures. J Clin Microbiol. 2005;43(6):2909–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Rigby S et al. Fluorescence in situ hybridization with peptide nucleic acid probes for rapid identification of Candida albicans directly from blood culture bottles. J Clin Microbiol. 2002;40(6):2182–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Forrest GN et al. Peptide nucleic acid fluorescence in situ hybridization-based identification of Candida albicans and its impact on mortality and antifungal therapy costs. J Clin Microbiol. 2006;44(9):3381–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Heil EL et al. Impact of a rapid peptide nucleic acid fluorescence in situ hybridization assay on treatment of Candida infections. Am J Health Syst Pharm. 2012;69(21):1910–4.

    Article  CAS  PubMed  Google Scholar 

  52. Aitkin S et al. Clinical practice patterns in hospitalized patients at risk for invasive candidiasis: role of antifungal stewardship programs in an era of rapid diagnostics. Ann Pharmacother. 2014;48(6):683–90.

    Article  Google Scholar 

  53. Bal AM et al. Antifungal step-down therapy based on hospital intravenous to oral switch policy and susceptibility testing in adult patients with candidaemia: a single centre experience. Int J Clin Pract. 2014;68(1):20–7. This article includes a review of automated step-down protocols that may represent a good starting point for antifungal stewardship programs.

    Article  CAS  PubMed  Google Scholar 

  54. Lopez-Medrano F et al. A non-compulsory stewardship programme for the management of antifungals in a university-affiliated hospital. Clin Microbiol Infect. 2013;19(1):56–61.

    Article  CAS  PubMed  Google Scholar 

  55. Reed EE et al. Improving the management of candidemia through antimicrobial stewardship interventions. Diagn Microbiol Infect Dis. 2014;78(2):157–61.

    Article  PubMed  Google Scholar 

  56. Nivoix Y et al. Adherence to recommendations for the use of antifungal agents in a tertiary care hospital. J Antimicrob Chemother. 2012;67(10):2506–13.

    Article  CAS  PubMed  Google Scholar 

  57. Andes D, Pascual A, Marchetti O. Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother. 2009;53(1):24–34.

    Article  CAS  PubMed  Google Scholar 

  58. Myers E, Dodds Ashley E. Antifungal drug therapeutic monitoring: what are the issues? Curr Clin Microbiol Rep. 2015;2(2):55–66.

    Article  Google Scholar 

  59. Durani U et al. Retrospective comparison of posaconazole levels in patients taking the delayed-release tablet versus the oral suspension. Antimicrob Agents Chemother. 2015;59(8):4914–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Jung DS, Tverdek FP, Kontoyiannis DP. Switching from posaconazole suspension to tablets increases serum drug levels in leukemia patients without clinically relevant hepatotoxicity. Antimicrob Agents Chemother. 2014;58(11):6993–5.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Cumpston A et al. Superior serum concentrations with posaconazole delayed-release tablets compared to suspension formulation in hematological malignancies. Antimicrob Agents Chemother. 2015;59(8):4424–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Miceli MH et al. Serum posaconazole levels among haematological cancer patients taking extended release tablets is affected by body weight and diarrhoea: single centre retrospective analysis. Mycoses. 2015;58(7):432–6.

    Article  CAS  PubMed  Google Scholar 

  63. Parkes LO, Cheng MP, Sheppard DC. Visual hallucinations associated with high posaconazole concentrations in serum. Antimicrob Agents Chemother. 2015;60(2):1170–1.

    Article  PubMed  Google Scholar 

  64. Schmitt-Hoffmann A et al. Multiple-dose pharmacokinetics and safety of the new antifungal triazole BAL4815 after intravenous infusion and oral administration of its prodrug, BAL8557, in healthy volunteers. Antimicrob Agents Chemother. 2006;50(1):286–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ashbee HR et al. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology. J Antimicrob Chemother. 2014;69(5):1162–76.

    Article  CAS  PubMed  Google Scholar 

  66. Hamada Y et al. Practice guidelines for therapeutic drug monitoring of voriconazole: a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring. J Infect Chemother. 2013;19(3):381–92.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Toth NR, Chambers RM, Davis SL. Implementation of a care bundle for antimicrobial stewardship. Am J Health Syst Pharm. 2010;67(9):746–9.

    Article  PubMed  Google Scholar 

  68. Antworth A et al. Impact of an antimicrobial stewardship program comprehensive care bundle on management of candidemia. Pharmacotherapy. 2013;33(2):137–43.

    Article  PubMed  Google Scholar 

  69. Mondain V et al. A 6-year antifungal stewardship programme in a teaching hospital. Infection. 2013;41(3):621–8. This article nicely outlines how multidisciplinary stewardship teams utilizing bundle care can impact compliance to national process of care measures for IFIs.

    Article  CAS  PubMed  Google Scholar 

  70. Valerio M et al. Training should be the first step toward an antifungal stewardship program. Enferm Infecc Microbiol Clin. 2015;33(4):221–7.

    Article  PubMed  Google Scholar 

  71. Ananda-Rajah MR, Slavin MA, Thursky KT. The case for antifungal stewardship. Curr Opin Infect Dis. 2012;25(1):107–15.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacy, University of Rochester Medical Center, 601 Elmwood Avenue, Box 638, Rochester, NY, 14642, USA

    Brittany Andruszko

  2. Division of Infectious Diseases, Duke University School of Medicine, 315 Trent Drive, Room 170 Hanes House, Durham, NC, 27710, USA

    Elizabeth Dodds Ashley

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  1. Brittany Andruszko
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Correspondence to Elizabeth Dodds Ashley.

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Brittany Andruszko declares no conflict of interest.

Elizabeth Dodds Ashley reports grants and personal fees from New York Council of Health Systems Pharmacists, the Hospital Association of New York State, UP to Date, and the University of Rochester Medical Center, outside the submitted work.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Mycology

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Andruszko, B., Dodds Ashley, E. Antifungal Stewardship: an Emerging Practice in Antimicrobial Stewardship. Curr Clin Micro Rpt 3, 111–119 (2016). https://doi.org/10.1007/s40588-016-0039-1

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