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- Title
Treatment of Cryptococcal Meningitis: How Have We Got Here and Where are We Going?
- Authors
Ngan, Nguyen Thi Thuy; Flower, Barnaby; Day, Jeremy N.
- Abstract
Cryptococcal meningitis is a devastating brain infection cause by encapsulated yeasts of the Cryptococcus genus. Exposure, through inhalation, is likely universal by adulthood, but symptomatic infection only occurs in a minority, in most cases, months or years after exposure. Disease has been described in almost all tissues, but it is the organism's tropism for the central nervous system that results in the most devastating illness. While invasive disease can occur in the immunocompetent, the greatest burden by far is in immunocompromised individuals, particularly people living with human immunodeficiency virus (HIV), organ transplant recipients and those on glucocorticoid therapy or other immunosuppressive drugs. Clinical presentation is variable, but diagnosis is usually straightforward, with cerebrospinal fluid microscopy, culture, and antigen testing proving significantly more sensitive than diagnostic tests for other brain infections. Although disease incidence has reduced since the advent of effective HIV therapy, mortality when disease occurs remains extremely high, and has changed little in recent decades. This Therapy in Practice review is an update of a talk first given by JND at the European Congress on Clinical Microbiology and Infectious Diseases in 2019 in the Netherlands. The review contextualizes the most recently published World Health Organization (WHO) guidelines for the treatment of HIV-associated cryptococcal meningitis in terms of the data from large, randomized, controlled trials published between 1997 and 2022. We discuss the rationale for induction and maintenance therapy and the efficacy and undesirable effects of the current therapeutic armamentarium of amphotericin, flucytosine and fluconazole. We address recent research into repurposed drugs such as sertraline and tamoxifen, and potential future treatment options, including the novel antifungals fosmanogepix, efungumab and oteseconazole, and non-pharmaceutical solutions such as neurapheresis cerebrospinal fluid filtration.
- Subjects
HIV infection complications; THERAPEUTIC use of glucocorticoids; WORLD Health Organization; HIV-positive persons; IMMUNOCOMPROMISED patients; MICROSCOPY; PATIENTS; MEDICAL protocols; CRYPTOCOCCUS neoformans; MENINGITIS; IMMUNOSUPPRESSIVE agents; CEREBROSPINAL fluid; TRANSPLANTATION of organs, tissues, etc.; DISEASE risk factors
- Publication
Drugs, 2022, Vol 82, Issue 12, p1237
- ISSN
0012-6667
- Publication type
Article
- DOI
10.1007/s40265-022-01757-5