Off-Label Treatments As Potential Accelerators in the Search for the Ideal Antifungal Treatment Of Cryptococcosis

Abstract

Cryptococcosis is an opportunistic mycosis that mainly affects immunosuppressed patients. The treatment is a combination of three antifungal agents: amphotericin B, 5-flucytosine and fluconazole. However, these drugs have many disadvantages, such as high nephrotoxicity, marketing bans in some countries and fungal resistance. One of the solutions to find possible new drugs is pharmacological repositioning. This work presents repositioned drugs as an alternative for new antifungal therapies for cryptococcosis. All the studies here were performed in vitro or in animal models, except for sertraline, which reached phase III in humans. There is still no pharmacological repositioning approval for cryptococcosis in humans, though this review shows the potential of repurposing as a rapid approach to finding new agents to treat cryptococcosis.

Keywords::

• antifungal
• cryptococcosis
• Cryptococcus
• off-label medication
• repositioning drugs

Author contributions

VAN, GRS Araújo and SFC contributed equally in the elaboration, writing and discussion of the article.

Financial & competing interests disclosure

This work was supported by the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES) (finance code 001) and Fundação de Amparo à Pesquisa do Rio de Janeiro (FAPERJ). 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.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES) (finance code 001) and Fundação de Amparo à Pesquisa do Rio de Janeiro (FAPERJ). 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.