Recent advances and future perspectives in the pharmacological treatment of Candida auris infections

ABSTRACT

Introduction

Candida auris is responsible for hospital outbreaks worldwide. Some C. auris isolates may show concomitant resistance to azoles, echinocandins, and polyenes, thereby possibly leaving clinicians with few therapeutic options.

Areas covered

Antifungal agents both in early and in late phases of clinical development showing anti-C. auris activity.

Expert opinion

The research on antifungal agents active against C. auris has made important steps forward in recent years: (i) the development of drugs with novel mechanisms of action, such as ibrexafungerp and fosmanogepix, could provide a valid option against C. auris strains resistant to one or more older antifungals, including pan-resistant strains; (ii) rezafungin could allow once weekly administration of an active drug in the case of echinocandin-susceptible isolates, providing an effective outpatient treatment, while at the same time relieving selective pressure on novel classes; (iii) the development of oral formulations could allow step-down therapy and/or early discharge, or even to avoid hospitalization in mild or noninvasive diseases; (iv) according to available data, these novel agents show a good safety profile and a low potential for drug–drug interactions.

KEYWORDS:

• Candida auris
• ibrexafungerp
• rezafungin
• fosmanogepix
• VT-1598
• encochleated amphotericin b
• echinocandins

Article highlights

• Some C. auris isolates may show concomitant resistance to azoles, echinocandins, and polyenes, thereby possibly leaving clinicians with combination regimens of unproven efficacy

• Echinocandins are currently the first-line choice for the treatment of invasive C. auris infections, primarily due to their good efficacy and safety profile, but also considering the high prevalence of resistance to azoles and the variable susceptibility to amphotericin B

• Some agents in phase 2 and 3 of clinical development may offer important alternatives with novel mechanisms of action, and may allow step-down therapy and early discharge owing to the availability of oral formulations

• The use of such novel agents cannot be separated from a high quality, comprehensive approach to the management of invasive candidiasis caused by C. auris, which also includes proper diagnostic and follow-up procedures, as well as an adequate source control whenever possible

Declaration of interest

Outside the submitted work, DRG reports honoraria from Stepstone Pharma GmbH and unconditional grants from MSD Italia, Correvio Italia, and Pfizer Inc. Outside the submitted work, MB has received funding for scientific advisory boards, travel and speaker honoraria from Angelini, Astellas, AstraZeneca, Basilea, Bayer, BioMérieux, Cidara, Correvio, Cubist, Menarini, Molteni, MSD, Nabriva, Paratek, Pfizer, Roche, Shionogi, Tetraphase, Thermo Fisher, and The Medicine Company. Outside the submitted work, MM received lecture and advisory board honoraria from Pfizer, MSD, Biotest, Gilead, Janssen. PK is supported by the German Federal Ministry of Research and Education and the State of North Rhine-Westphalia, Germany and has received non-financial scientific grants from Miltenyi Biotec GmbH, Bergisch Gladbach, Germany, and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany, and received lecture honoraria from and/or is advisor to Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, MSD Sharp & Dohme GmbH, Noxxon N.V., and University Hospital, LMU Munich outside the submitted work. OAC is supported by the German Federal Ministry of Research and Education, by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – CECAD, EXC 2030 – 390,661,388, by European Union’s Horizon 2020 Research and Innovation Programme (N0. 101,037,867) and has received research grants from, is an advisor to, or received lecture honoraria from Actelion, Allecra Therapeutics, Al-Jazeera Pharmaceuticals, Amplyx, Astellas, Basilea, Biosys, Cidara, Da Volterra, Entasis, F2G, Gilead, Grupo Biotoscana, Immunic, IQVIA, Janssen, Matinas, Medicines Company, MedPace, Melinta Therapeutics, Menarini, Merck/MSD, Mylan, Nabriva, Noxxon, Octapharma, Paratek, Pfizer, PSI, Roche Diagnostics, Scynexis, and Shionogi. CS and LM have no conflicts of interest to disclose.

Reviewer disclosures

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

Additional information

Funding

This work was not funded.