Invasive fungal infections are a substantial medical concern, particularly in immunocompromised patients. As medical advances increase the size of this population, invasive fungal infections will continue to be a large medical issue.
Progress has been made recently in developing antifungal agents, but more agents, particularly those with a broad spectrum and low toxicity, are needed. New formulations of existing antifungals are being developed to address these issues.
Novel antifungal pathways and targets are being used to identify potential antifungal agents with new mechanisms of action, which could lead to the development of new drugs.
Alternative strategies to target drugs to infection sites, to repurpose agents for antifungal use and to use the immune system as adjunctive therapies are discussed in this Review.
Invasive fungal infections continue to appear in record numbers as the immunocompromised population of the world increases, owing partially to the increased number of individuals who are infected with HIV and partially to the successful treatment of serious underlying diseases. The effectiveness of current antifungal therapies — polyenes, flucytosine, azoles and echinocandins (as monotherapies or in combinations for prophylaxis, or as empiric, pre-emptive or specific therapies) — in the management of these infections has plateaued. Although these drugs are clinically useful, they have several limitations, such as off-target toxicity, and drug-resistant fungi are now emerging. New antifungals are therefore needed. In this Review, I discuss the robust and dynamic antifungal pipeline, including results from preclinical academic efforts through to pharmaceutical industry products, and describe the targets, strategies, compounds and potential outcomes.
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The author has research support from Public Health Service Grants (AI73896, AI04533, AI93257).
The author declares research grants, consulting arrangements, honorariums and advisory committees from the following companies: Merck & Co., Astellas, Pfizer Inc, F2G, Vical, Arno Therapeutics, Cidara, Scynexis, Viamet, Matinas BioPharma, Amplyx Pharmaceuticals and Teva Pharmaceutical Industries.
Chronic fungal infections of skin and soft tissue.
- T2 MRI
(Magnetic resonance imaging). A testing system from T2 Biosystems that uses advances in nanotechnology and molecular biology to detect microorganisms directly from body fluids.
- GAIN Act
The Generating Antibiotic Incentives Now (GAIN) Act by the US Federal Government is legislation that aims to stimulate antimicrobial discovery.
- Orphan Drug Act
The Orphan Drug Act enables the US Food and Drug Administration (FDA) to designate a treatment as being developed for a rare disease upon request from a sponsor.
- Fast Track
Fast Track is a US Food and Drug Administration (FDA) designation for expedited review of drugs to fill unmet medical needs, as requested by a drug company.
- Virulence composite
The genetic and phenotypic traits that encompass pathogenicity.
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Perfect, J. The antifungal pipeline: a reality check. Nat Rev Drug Discov 16, 603–616 (2017). https://doi.org/10.1038/nrd.2017.46
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