The antifungal pipeline: a reality check

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Abstract

Invasive fungal infections are a major medical concern, particularly in immunocompromised patients. In this Review, Perfect discusses the antifungal pipeline, including advances in the currently used drug classes, novel molecular targets, drugs that could be repurposed from other areas and the use of immune-directed therapies.

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Most cited references 131

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Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.

John R. Perfect, William E. Dismukes, Francoise Dromer … (2010)

Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.

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Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.

Peter Pappas, Carol A Kauffman, David Andes … (2016)

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

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Antifungal agents: mechanisms of action

Frank Odds, Alistair J.P. Brown, Neil Gow (2003)

Clinical needs for novel antifungal agents have altered steadily with the rise and fall of AIDS-related mycoses, and the change in spectrum of fatal disseminated fungal infections that has accompanied changes in therapeutic immunosuppressive therapies. The search for new molecular targets for antifungals has generated considerable research using modern genomic approaches, so far without generating new agents for clinical use. Meanwhile, six new antifungal agents have just reached, or are approaching, the clinic. Three are new triazoles, with extremely broad antifungal spectra, and three are echinocandins, which inhibit synthesis of fungal cell wall polysaccharides--a new mode of action. In addition, the sordarins represent a novel class of agents that inhibit fungal protein synthesis. This review describes the targets and mechanisms of action of all classes of antifungal agents in clinical use or with clinical potential.

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Author and article information

Journal

Title: Nature Reviews Drug Discovery

Abbreviated Title: Nat Rev Drug Discov

Publisher: Springer Nature

ISSN (Print): 1474-1776

ISSN (Electronic): 1474-1784

Publication date Created: May 12 2017

Publication date (Print): May 12 2017

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Article

DOI: 10.1038/nrd.2017.46

PubMed ID: 28496146

SO-VID: 4f09a872-368d-49c3-9276-8a7bde1e0d45

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The antifungal pipeline: a reality check

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Abstract

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HLA-G and immune tolerance in pregnancy

Most cited references 131

Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.

Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.

Antifungal agents: mechanisms of action

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