Current and promising pharmacotherapeutic options for candidiasis

ABSTRACT

Introduction: Candida spp. are commensal yeasts capable of causing infections such as superficial, oral, vaginal, or systemic infections. Despite medical advances, the antifungal pharmacopeia remains limited and the development of alternative strategies is needed.

Areas covered: We discuss available treatments for Candida spp. infections, highlighting advantages and limitations related to pharmacokinetics, cytotoxicity, and antimicrobial resistance. Moreover, we present new perspectives to improve the activity of the available antifungals, discussing their immunomodulatory potential and advances on drug delivery carriers. New therapeutic approaches are presented including recent synthesized antifungal compounds (Enchochleated-Amphotericin B, tetrazoles, rezafungin, enfumafungin, manogepix and arylamidine); drug repurposing using a diversity of antibacterial, antiviral and non-antimicrobial drugs; combination therapies with different compounds or photodynamic therapy; and innovations based on nano-particulate delivery systems.

Expert opinion: With the lack of novel drugs, the available assets must be leveraged to their best advantage through modifications that enhance delivery, efficacy, and solubility. However, these efforts are met with continuous challenges presented by microbes in their infinite plight to resist and survive therapeutic drugs. The pharmacotherapeutic options in development need to focus on new antimicrobial targets. The success of each antimicrobial agent brings strategic insights to the next phased approach in treatingCandida spp. infections.

KEYWORDS:

• Candida spp.
• antifungal compounds
• drug repurposing
• drug combination
• drug delivery

Article highlights

• Enchochleated-Amphotericin B (Coch-AmB), tetrazoles, rezafungin, enfumafungin, manogepix and arylamidine are new promising antifungal drugs.

• Drug repurposing using antibacterial, antiviral, and non-antimicrobial drugs can accelerate the introduction of new antifungal agents into clinical practice.

• Drug combinations are attractive options that can enhance the antifungal activities and impair development of antifungal resistance.

• Innovative drug delivery systems for antifungal compounds have been successfully developed using solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), polymeric nanoparticles, and metal-based nanoparticles.

• The success of each antimicrobial agent brings strategic insights to the next phased approach in treating Candida spp. infections.

This box summarizes key points contained in the article.

Declaration of interest

E Mylonakis participates in the Cidara_ ReSTORE multicenter trial and in the past has received grant support from Synexis, Sanofi, T2 Biosystems and Astellas. 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.

Reviewer Disclosures

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

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

JC Junqueira was supported by the Brazilian National Council for Scientific and Technological Development (CNPq 306330/2018-0) and the U. S. Office of Naval Research Global (ONRglobal N62909-20-1-2034). L Scorzoni has also received a Coordination for the Improvement of Higher Education Personnel (CAPES) scholarship while BB Fuchs was supported by NIH grant P20 GM121344.