Current recommendations and importance of antifungal stewardship for the management of invasive candidiasis

Abstract

Invasive candidiasis can have a major effect on patient prognosis and medical economics. Quickly eliminating the focus of the infection and administering appropriate antifungal therapy are important. Clinical guidelines for invasive candidiasis have been issued in the USA, Europe and recently in Japan. The purpose of this review is to summarize the current recommendations on how to diagnose and treat invasive candidiasis based on the evidence gathered to date and by referencing guidelines from various countries. Echinocandin antifungals play a central role in the prevention and treatment of invasive candidiasis although a recent increase in echinocandin-resistant Candida glabrata is seen as problematic. In the future, promoting the appropriate use of antifungal agents by antifungal stewardship teams will be necessary to suppress adverse effects, appearance of resistant strains and unnecessary medical expenses, as well as improve positive clinical outcomes and prognoses.

Keywords:

• antifungal resistance
• antifungal stewardship
• Candida glabrata
• candidemia
• echinocandin
• invasive candidiasis

Financial & competing interests disclosure

T Miyazaki received honoraria, consultation fees, and research grants from Astellas Pharma Inc., Dainippon Sumitomo Pharma Co., MSD (Merck & Co.), and Pfizer Inc. S Kohno received honoraria, consultation fees, and research grants from Astellas Pharma Inc., Dainippon Sumitomo Pharma Co., MSD (Merck & Co.), and Pfizer Inc. This work was partially supported by the Grant-in-Aid for Scientific Research (no. 24791027 to T Miyazaki and no. 21390305 to S Kohno) from the Japanese Ministry of Education, Culture, Sports, Science and Technology and by a grant from the Ministry of Health, Labour and Welfare (Research Program on Emerging and Re-emerging Infectious Diseases, H25-shinko-ippan-006 to both authors). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Invasive candidiasis can have a huge impact on patient prognosis and medical economics. Quickly removing central venous catheters and administering appropriate antifungal therapy are important.

• The therapeutic agent should be selected based on a comprehensive evaluation of the pathogenic species, severity, presence of complications and other factors, as well as an understanding of the antifungal spectrum of the antifungal agent, organ migration, side effects and drug interactions.

• The clinical effect should be evaluated 3–5 days after beginning treatment, and alternative drugs should be considered as necessary.

• Complicating endophthalmitis and endocarditis should be actively tested for, as these can affect therapeutic drug selection and treatment duration.

• The recommended treatment duration for candidemia without obvious metastatic complications is 2 weeks after symptoms caused by candidemia improve and confirmation of a negative blood culture result. If possible, stepping down to an oral medication should be considered.

• Complying with important bundle elements when managing cases of invasive candidiasis contributes to improved clinical effectiveness and prognosis.

• Echinocandins currently play a central role in the prevention and treatment of invasive candidiasis, but the recent increase in cases of echinocandin-resistant C. glabrata is problematic.

• Development of non-culture-based molecular diagnostic tools will likely aid the rapid selection of an appropriate antifungal agent and suppress unnecessary drug usage.

• Normalizing treatment methods will not only help eliminate the unnecessary use of antifungal agents but also improve clinical effectiveness and suppress adverse effects and resistant strains, which would reduce secondary medical expenses.

• Promoting AFS programs with teams composed of clinicians, pharmacists, laboratory technicians and others is important for addressing the aforementioned issues.