Clinical Pearls & Morning Reports
Published September 30, 2020
Cryptococcus neoformans is an opportunistic organism that is inhaled as an aerosolized particle from bird droppings, soil, and decaying wood. Immunosuppression confers a predisposition to both acute cryptococcal infection and reactivation of latent infection. Read the NEJM Clinical Problem-Solving Article here.
Who is particularly at risk for C. neoformans infection?
A: C. neoformans is an encapsulated yeast. There are multiple subspecies of cryptococcus, but C. neoformans accounts for 95% of all cryptococcal infections. The incidence of cryptococcal infections increased in the 1980s with the emergence of human immunodeficiency virus infection and acquired immunodeficiency syndrome. Antiretroviral therapy has since reduced the incidence of cryptococcal infections in this population. Patients at particularly high risk for C. neoformans infection include those who have undergone stem-cell or solid-organ transplantation or who are receiving targeted immunotherapy.
Q: How is cryptococcal meningitis diagnosed?
A: The diagnosis of cryptococcal meningitis is made by culturing the cerebrospinal fluid (CSF), but it takes an average of 7 days for cultures to grow. The serum and CSF tests for cryptococcal antigen are useful adjunctive tests that can be performed quickly and have a high sensitivity for the detection of C. neoformans.
A: Cryptococcus can involve nearly any organ system, but it most commonly involves the lungs, central nervous system (CNS), skin, and bones. CNS involvement by C. neoformans can cause headaches, lethargy, fever, meningismus, vision defects, sensory deficits, and cranial nerve palsies. Symptoms may manifest indolently or with a more rapid onset in cases of severe immunosuppression. As yeast in the CSF aggregates, it can obstruct the outflow of CSF, resulting in increased intracranial pressure (>25 cm of water). The increased intracranial pressure can worsen after treatment is initiated, since the destruction of yeast further compounds CSF outflow obstruction. In two case series involving patients with proven cryptococcal meningitis (confirmed histologically and by culture), follow-up imaging of the head revealed rates of lacunar infarction of 13% and 26%. It is thought that cryptococcal meningitis causes a small-vessel vasculitis that results in endothelial injury and ischemia.
A: Guideline-based treatment for cryptococcal meningitis consists of three phases: induction, consolidation, and maintenance therapy. Standard induction treatment includes a combination of intravenous liposomal amphotericin B and flucytosine for 2 to 4 weeks. This treatment is followed by consolidation therapy with fluconazole for 8 weeks. Combination induction therapy has been shown to result in significantly fewer deaths than amphotericin monotherapy. After completion of induction and consolidation therapy, maintenance suppressive therapy with lower-dose fluconazole is continued for up to 1 year to prevent recurrence of disease.