July 2, 2015: Persistent Cryptococcal Meningitis

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July 2, 2015

Intraventricular neurocysticercosis

To begin, cryptococcal meningitis is a fungal infection affecting approximately 1 per 100,000 people in the United States annually, with a predilection for individuals with impaired cellular immunity. Prognosis and mortality rates are dependent on a number of factors, including the host’s immunological status, time to treatment, and intracranial pressure at time of diagnosis. Treatment with antifungals typically involves some variation of induction therapy with amphotericin B and flucytosine for two weeks, then consolidation therapy with fluconazole for eight weeks, followed by long-term maintenance or suppressive therapy with fluconazole. Despite significant evidence for the efficiency of this approach, persistent infections still occur. In antiretroviral-naïve patients with HIV who are treated with antifungal therapy, mortality is still as high as one third at ten weeks.

So how do we define chronic cryptococcal meningitis? Simply put, it is the persistence of positive cerebral spinal fluid cultures after four weeks of proven antifungal therapy. Complications such as refractory raised intracranial pressure can lead to severe chronic headaches as well as the life-threatening risk of herniation. A persistent infection should be distinguished from a relapse, as it is not attributable to inadequate induction therapy or poor compliance with maintenance therapy.


  1. C. neoformans Infection Statistics. In: Centers for Disease Control and Prevention [online]. Available at: Accessed February 13, 2014.
  2. Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clinical Infectious Diseases 2010; 50: 291-321.
  3. Jarvis JN, Bicanic T, Loyse A, et al. Determinants of Mortality in a Combined Cohort of 501 Patients With HIV-Associated Cryptococcal Meningitis: Implications for Improving Outcomes. Clinical Infectious Diseases 2014; 58: 736–745.

Submitted by Sarah Wesley MD, Mount Sinai Beth Israel Medical Center, Department of Neurology.

Disclosures: Dr. Wesley is a member of the Residents & Fellows Section of Neurology.

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