What I Have Learned About Infectious Diseases With My Sleeves Rolled Up

Karen L. Roos, MD


Semin Neurol. 2002;22(1) 

In This Article

Cryptococcal Meningitis

Cryptococcal meningitis occurs in both immunocompetent and immunosuppressed individuals and is the most common pathogen to cause fungal meningitis. The two major risk factors for cryptococcal meningitis are immunosuppression from human immunodeficiency virus (HIV) infection or organ transplantation and prednisone therapy. Prednisone doses of 20 mg/d or greater increase the risk for cryptococcal meningitis.[18] The most common symptoms of cryptococcal meningitis are headache, fever, and malaise but cryptococcal meningitis may also present with nausea and vomiting, meningeal signs, altered mental status, and cranial nerve palsies.

The treatment of cryptococcal meningitis in non-AIDS patients includes either a combination of intravenous amphotericin B (0.5 to 0.7 mg/kg/d) plus oral flucytosine (25 mg/kg four times daily) or Ambisome 5 mg/kg/d. A combination of amphotericin B plus flucytosine or Ambisome monotherapy is given for 2 weeks or until the CSF culture is sterile. Fluconazole 400 to 800 mg/d is begun and continued for 8 to 10 weeks. Corticosteroid therapy should not be used in the treatment of cryptococcal meningitis. A combination of amphotericin B 0.7 to 1.0 mg/kg/d with flucytosine 25 mg/kg four times daily is recommended for the treatment of cryptococcal meningitis in AIDS patients. This induction therapy is followed by fluconazole 400 mg/d for 8 weeks, and then the dose is decreased to 200 mg/d. In both non-AIDS and AIDS patients, the CSF should be examined at the end of the 2-week period of induction therapy and again at 8 to 10 weeks when consideration is being given to either discontinuing fluconazole in non-AIDS patients or reducing the daily dose of fluconazole in AIDS patients. At these two times, it is the CSF culture result that is important, not the CSF cryptococcal antigen titer. If the CSF culture is sterile, a change in therapy can be made. If the CSF culture is not sterile, amphotericin B or Ambisome should be continued. If they have been discontinued, therapy with one of these antifungal agents should be reinitiated.

The most common adverse reaction to amphotericin B is fever, chills, and hypotension 1 to 3 hours after initiation of intravenous infusion. Renal insufficiency and anemia are common adverse reactions during the course of therapy and may necessitate the interruption of therapy or reduction of dose. The most common adverse reaction to flucytosine is leukopenia. The most common adverse reactions to fluconazole are nausea, vomiting, and elevated serum transaminases. Not all patients can tolerate fluconazole for 8 to 10 weeks because of the adverse reaction of nausea and vomiting. For these patients, a second course of Ambisome 5 mg/kg/d for 2 weeks may be beneficial.

The management of increased intracranial pressure is critical to a successful outcome from cryptococcal meningitis. Intracranial pressure should be measured at the time of the initial lumbar puncture, at the completion of induction therapy, and any time during the course of the illness when the patient has a change in mental status or a change in the neurological examination (spastic gait, pathologically brisk reflexes, cranial nerve abnormalities, visual changes). The increased intracranial pressure is due to altered CSF hemodynamics and should be managed with either daily lumbar punctures (to decrease CSF pressure by 50% and maintain CSF pressure at <300 mm H2), a ventriculostomy, or a ventriculoperitoneal shunt.


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