An introduction to the future of echinocandin therapy

Since their introduction, nearly 20 years ago, echinocandins have become a cornerstone in invasive candidiasis treatment and one of the main classes of antifungal treatment and prophylaxis.^1,2 However, the unmet and evolving needs in antifungal therapy call for improvements to current approaches and the development of new options. In addition to ensuring safety and efficacy, there are concerns about resistance, and advances in the treatment of underlying disease (the increasingly diverse polypharmacy of immunosuppressive and immunomodulatory agents, chemotherapies and biologics; risks and management of drug–drug interactions; longer life expectancies and the need for longer durations of prophylaxis to prevent late-onset infections) further raise the demands placed on modern antifungal therapy.

This Supplement to the Journal of Antimicrobial Chemotherapy presents an outlook on the future of echinocandin therapy with these goals in mind: how might current use be improved, and how might newer options augment treatment and prophylaxis strategies in the future?

In the first paper, Lamoth and colleagues³ review the changing epidemiology of invasive candidiasis. In addition to antifungal resistance concerns and shifts in distribution to non-albicans species, recent developments in Candida auris have raised questions about the current antifungal armoury. Although the importance of C. auris is not yet fully understood, echinocandin therapy may help answer the international call to arms that has been raised to meet the challenge.⁴ The emergence of C. auris is the latest example of a dynamic landscape that will require novel agents and stewardship practices to address the challenges of evolving mycoses. The next article in the Supplement, ‘What has changed in the treatment of invasive candidiasis? A look at the past 10 years and ahead’,⁵ takes a longitudinal view, from the past decade of experience in treating invasive candidiasis to the latest evidence that may inform future practice. Advances in diagnostic methods, approaches to prophylactic, pre-emptive and empirical therapy, and new drugs in development, including the novel once-weekly echinocandin rezafungin acetate (previously CD101),^6–13 are poised to benefit the overarching goal of treatment: timely initiation of safe and efficacious antifungal therapy. The third paper, by Mourad and Perfect,¹⁴ reviews the tolerability of current and investigational agents, as part of the evaluation of risks versus benefits that may influence treatment selection.

The ‘silent epidemic’ of antifungal underdosing is an emerging but critical item on the antifungal research agenda and is discussed in two articles in the Supplement. First, Pea and Lewis¹⁵ review the departure from a one-size-fits-all approach to individualized therapy based on the pharmacokinetic/pharmacodynamic (PK/PD) profile of a drug and patient-specific factors, such as polymorphisms, concomitant medications and drug–drug interaction risks, and special population considerations (for example, obesity, renal impairment/dialysis, hepatic impairment). Next, Bader and colleagues¹⁶ focus on echinocandin dosing and present a review of recent PK/PD research on current and investigational echinocandins in their paper ‘We can do better: a fresh look at echinocandin dosing’. Their findings overall, and specifically with a single-dose regimen of rezafungin acetate, may have significant implications for PK/PD-optimized antifungal dosing, the treatment of resistant isolates, and situations requiring longer durations of therapy.

Use of antifungal prophylaxis has increased and will likely continue with advances in the treatment of underlying diseases that render patients immunodeficient and at increased risk of opportunistic fungal infection. Echinocandin use in prophylaxis has been limited by dosing requirements, but their safety, efficacy and predictable pharmacokinetics relative to other agents and the potential availability of newer agents with additional dosing options and expanded coverage (Pneumocystis pneumonia, for instance) suggest a greater role in the future of echinocandin therapy. These topics are discussed by Giannella and colleagues¹⁷ in their review of echinocandin prophylaxis in liver, lung and other solid organ transplant recipients, and by Epstein and colleagues¹⁸ in their review of the experience with and rationale for echinocandin prophylaxis in HSCT recipients and patients with haematological malignancies.

The final article in this Supplement, ‘Biofilms and beyond: expanding echinocandin utility’,¹⁹ reviews leading areas of echinocandin research, from the development of new agents to additional applications for use, such as in the treatment of biofilms, dermatophytes and C. auris. Nascent findings relating to the mycobiome represent a truly novel and intriguing area of study. These active research efforts reflect the potential of the class and portend well for the future of echinocandin therapy.

Funding

This article is part of a supplement sponsored by Cidara Therapeutics, Inc. Editorial support was provided by T. Chung (Scribant Medical) and funded by Cidara Therapeutics.

Transparency declarations

Dr Bassetti has participated in advisory boards and/or received speaker honoraria from Achaogen, Angelini, Astellas, AstraZeneca, Bayer, Basilea, Cidara, Gilead, Menarini, MSD, Pfizer, The Medicines Company, Tetraphase and Vifor.

 The author received no compensation for contributing to the supplement. This article was developed and published based on the author’s approval.

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