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      The war on cryptococcosis: A Review of the antifungal arsenal

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          Abstract

          Cryptococcal meningitis is the most common central nervous system infection in the world today. It occurs primarily, but not exclusively, in immunocompromised individuals and despite substantial improvement in management of clinical events like AIDS, the numbers of cases of cryptococcosis remain very high. Unfortunately, despite several antifungal agents available for treatment, morbidity and mortality rates remain high with this fungal infection. In this Review, we will describe the treatments and strategies for success, identify the failures, and provide insights into the future developments / improvements for management. This sugar-coated yeast can play havoc within the human brain. Our goals must be to either prevent or diagnose disease early and treat aggressively with all our clinical tools when disease is detected.

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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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            The antifungal pipeline: a reality check

            John Perfect (2017)
            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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              Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy

              Peter R. Williamson, Joseph Jarvis, Anil Panackal … (2016)
              HIV-associated cryptococcal meningitis is by far the most common cause of adult meningitis in many areas of the world that have high HIV seroprevalence. In most areas in Sub-Saharan Africa, the incidence of cryptococcal meningitis is not decreasing despite availability of antiretroviral therapy, because of
              Article 0 comments Cited 166 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Mem Inst Oswaldo Cruz
                Journal ID (iso-abbrev): Mem. Inst. Oswaldo Cruz
                Journal ID (publisher-id): mioc
                Title: Memórias do Instituto Oswaldo Cruz
                Publisher: Instituto Oswaldo Cruz, Ministério da Saúde
                ISSN (Print): 0074-0276
                ISSN (Electronic): 1678-8060
                Publication date (Electronic): 19 February 2018
                Publication date Collection: 2018
                Volume: 113
                Issue: 7
                Electronic Location Identifier: e170391
                Affiliations
                [1]Duke University Medical Center, Department of Medicine, Division of Infectious Diseases, Durham, NC, USA
                Author notes
                [+ ] Corresponding author: john.perfect@ 123456duke.edu

                AUTHORS’ CONTRIBUTION

                Dr Mourad and Dr Perfect contributed to the article by conducting the appropriate literature review, drafting the article and revising important content; Dr Perfect gave final approval of the version to be submitted.

                Article
                Other ID: 00202
                DOI: 10.1590/0074-02760170391
                PMC ID: 5851043
                PubMed ID: 29513785
                SO-VID: b715d481-522d-4f93-9698-4bd06454e01f
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 25 September 2017
                Date accepted : 23 November 2017
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 82, Pages: 1
                Categories
                Subject: Review

                Keywords: cryptococcosis,cryptococcus,cryptococcal meningitis,antifungal drugs
                Data availability:
                Keywords: cryptococcosis, cryptococcus, cryptococcal meningitis, antifungal drugs

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