Cryptococcal meningitis

Glucose >50% of the serum values Acute bacterial meningitis Tuberculosis meningitis Cryptococcal meningitis Listeria meningitis Neurosarcoidosis ... 

Intra-abdominal infection Meningitis (cryptococcal, fungal)... 

Fungal meningitis CSF culture, CSF and serum cryptococcal antigen titers, microscopic examination of CSF specimens... 

C. neoformans is strongly neurotropic and readily disseminates from the lung to the CNS, specifically the lep-tomeninges, and occasionally the parenchyma of the brain. The clinical characteristics of cryptococcal meningitis differ somewhat, however, between patients with and without underlying AIDS. In patients without AIDS, disease presentation is more insidious and symptoms such as dizziness,... 

Cryptococcal meningitis is fatal if left untreated. Because pneumonia frequently precedes dissemination of disease and subsequent meningitis, all patients with culture-, histopathology-, or serology-proven disease should receive antifungal therapy. In patients with isolated pulmonary cryptococcosis, fluconazole is generally considered to be the therapy of choice (see Table 81-2).37 Alternatively, itraconazole or combination therapy (fluconazole plus flucytosine) has also been used with some success in patients. 

A 26-year-old female with acquired immunodeficiency syndrome (AIDS) develops cryptococcal meningitis. She refuses all intravenous medication. Which antifungal agent can be given orally to treat the meningeal infection ... 

In the United States, cryptococcal meningitis is the most common form of fungal meningitis and is a major cause of morbidity and mortality in immunosuppressed patients. 

Fever and a history of headaches are the most common symptoms of cryptococcal meningitis, although altered mentation and evidence of focal neurologic deficits may be present. Diagnosis is based on the presence of a positive CSF, blood, sputum, or urine culture for Cryptococcus neoformans. 

Due to the high relapse rate following acute therapy for C. neoformans, AIDS patients require lifelong maintenance or suppressive therapy. The standard of care for AIDS-associated cryptococcal meningitis is primary therapy, generally using amphotericin B with or without flucytosine followed by maintenance therapy with fluconazole for the fife of the patient. 

In the non-AIDS patient, the symptoms of cryptococcal meningitis are nonspecific. Headache, fever, nausea, vomiting, mental status changes, and neck stiffness are generally observed. In AIDS patients, fever and headache are common, but meningismus and photophobia are much less common than in non-AIDS patients. 

Examination of cerebrospinal fluid (CSF) in patients with cryptococcal meningitis generally reveals an elevated opening pressure, CSF pleocytosis (usually lymphocytes), leukocytosis, a decreased CSF glucose, an elevated CSF protein, and a positive cryptococcal antigen. 

The combination of amphotericin B with flucytosine for 6 weeks is often used for treatment of cryptococcal meningitis. An alternative is amphotericin B for 2 weeks followed by fluconazole for an additional 8 to 10 weeks. Suppressive therapy with fluconazole 200 mg/day for 6 to 12 months is optional. 

The use of intrathecal amphotericin B is not recommended for the treatment of cryptococcal meningitis except in very ill patients or in those with recurrent or progressive disease despite aggressive IV amphotericin B therapy. The dosage of amphotericin B employed is usually 0.5 mg administered via the lumbar, cisternal, or intraventricular (via an Ommaya reservoir) route two or three times weekly. 

Amphotericin B with flucytosine is the initial treatment of choice for acute therapy of cryptococcal meningitis in AIDS patients. Many clinicians will initiate therapy with amphotericin B, 0.7 mg/kg/day IV (with flucytosine, 100 mg/kg/day). After 2 weeks, consolidation therapy with either itraconazole 400 mg/day orally or fluconazole 400 mg/day orally can be administered for 8 weeks or until CSF cultures are negative. Lifelong therapy with fluconazole is then recommended. 

Cryptococcal meningitis in HIV Treatment of cryptococcal meningitis in HIV-infected patients AmBisome only). 

Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent relapse... 

Cryptococcal meningitis 400 mg on the first day, followed by 200 mg once daily. A dosage of 400 mg once daily may be used, based on the patient s response to therapy. The duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. The dosage of fluconazole for suppression of relapse of cryptococcal meningitis in patients with AIDS is 200 mg once daily. 

Flucytosine is an oral antifungal pro-drug. It has to be enzymatically deaminated by the fungi to the active metabolite, fluorouracil. Fluorouracil inhibits thymidylate synthetase and DNA synthesis. Its indications are treatment of cryptococcal meningitis and serious systemic candidiasis. Resistance develops rapidly, due to altered drug-permeability. For this reason Amphotericin B and flucytosine are often given in combination as they have synergistic effects. 

Cryptococcal meningitis Lumbar puncture Serum Cryptococcal antigen (sCRAG) India-ink preparation Crypto Ag titer... 

Intravenous amphotericin plus intravenous or oral flucytosine is the traditional treatment. There is an increasing role for fluconazole, particularly in maintenance therapy in acquired immunodeficiency syndrome (AIDS). The treatment for Cryptococcal meningitis is discussed in Table 15. 

A significant decrease in mortality from deep-seated mycoses was noted among bone marrow transplant recipients treated prophylactically with fluconazole, but similar benefits have not been seen in leukemia patients receiving prophylactic fluconazole. Fluconazole taken prophylactically by end-stage AIDS patients can reduce the incidence of cryptococcal meningitis, esophageal candidiasis, and superficial fungal infections. 

Despite negligible cerebrospinal fluid concentrations, itraconazole shows promise in the treatment of cryptococcal and coccidioidal meningitis. Additional uses for itraconazole include treatment of vaginal candidiasis, tinea versicolor, dermatophyte infections, and onychomycosis. Fungal naU infections account for most use of this drug in the outpatient setting. 

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