Existing and emerging therapies for the treatment of invasive candidiasis and candidemia

ABSTRACT

Introduction

Invasive candidiasis or candidemia is a severe infection affecting more than 250,000 people worldwide every year. It is present in up to 16% of ICU patients. The prognosis of these infections is unfavorable, with global death estimated around 50,000 per year, which corresponds to up to 40% depending on patient severity and comorbidities. Therapeutic failure is not rare due to the emergence of multiresistant strains and of new species poorly responsive to current therapies like Candida auris.

Areas covered

We first review the positioning of antifungal drugs used to treat candidiasis, namely polyenes, azoles, echinocandins and pyrimidine analogues. We then discuss the progresses brought by new formulations, new derivatives within these classes, compounds acting on new targets or repurposed drugs in terms of pharmacokinetic profile, spectrum of activity, potency, safety or risk of drug-drug interactions.

Expert opinion

While new formulations (amphotericin B cochleate) improve oral bioavailability of the corresponding drugs, new azoles or echinocandins offer higher potency including against strains resistant to former generations of drugs. Repurposed drugs show synergism with current therapies in vitro. Results from ongoing and future clinical trials will be decisive to establish the interest for these drugs in our arsenal.

KEYWORDS:

• Antifungals
• invasive candidiasis
• candidemia
• cell wall
• fungi cell
• plasma membrane
• severe infection

Acknowledgments

Our thoughts are with Prof David de Bels (first author) who passed away at the age of 56 years before the revision of this manuscript. We would like to acknowledge the tremendous input of Dr Ibrahim Bousbiat from CHU Brugmann and ULB university.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was notfunded.