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

Expert Opin Emerg Drugs. 2022 Dec;27(4):405-416. doi: 10.1080/14728214.2022.2142207. Epub 2022 Nov 11.

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; candidemia; cell wall; fungi cell; invasive candidiasis; plasma membrane; severe infection.

MeSH terms

  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Azoles / pharmacology
  • Azoles / therapeutic use
  • Candidemia* / drug therapy
  • Candidiasis, Invasive* / drug therapy
  • Echinocandins / therapeutic use
  • Humans

Substances

  • Antifungal Agents
  • Echinocandins
  • Azoles

Supplementary concepts

  • Systemic candidiasis