Treatment of Cryptococcal Meningitis: How Have We Got Here and Where are We Going?

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.

MRI-Guided Stereotactic Craniotomy to Set the Diagnosis of CNS Cryptococcosis. Case Report and Review of the International Literature

“…The brain imaging testing in our case, including brain CT and MRI were consistent with the findings reported in the international literature including the low-density on T1-weighted and high-density lesions on T2-weighted MRI images of the cryptococcomas [12,13]. While the majority of the cases are being diagnosed by blood and CSF laboratory analysis, in our case that the initial results were within normal range, and there was a high indication of CNS infection from the brain MRI findings, the diagnosis was set by surgically removal of the lesion and subsequent histopathology [14,15].…”

Neutron Scattering Analysis ofCryptococcus neoformansPolysaccharide Reveals Solution Rigidity and Repeating Fractal-like Structural Patterns

“…Based solely on the water-free composition, the neutron scattering length density (SLD) of polysaccharides in H O is expected to range from 1×10 -6 Å -2 to 2×10 -6 Å -2 (the SLD of pure H O is -0.56×10 -6 Å -2 ) 33 . The flat scattering profiles observed in the exo-PS samples are consistent with their high hydration state and a significant contribution of incoherent scattering originating from the hydrogen atoms within the samples ( Figure S2 ).…”

Cerebral Cryptococcosis Associated with CD4+ T-lymphocytopenia in Non-HIV Patients after SARS-CoV-2 Infection: Case Series in a Specialized Institute in Lima, Peru

“…Cerebral cryptococcosis is an opportunistic infection that mainly affects patients with Human Immunodeficiency Virus (HIV) infection with CD4+ T-lymphocyte counts lower than 100 cells/µL, and also in transplant recipients, hematological malignancies, idiopathic CD4 lymphocytopenia, and users of prolonged corticosteroid therapy or other immunosuppressants [ 8 ]. Its presentation in immunocompetent hosts is infrequent.…”