Cryptococcosis : Diagnosis, Pathophysiology And Treatmet
Cryptococcosis is a noncontagious, systemic mycotic infection caused by the ubiquitous encapsulated soil yeast Cryptococcus neoformans.
- Primary cryptococcosis in humans almost always occurs in the lungs. Symptomatic infections are usually manifested by cough, rales, and shortness of breath that generally resolve spontaneously.
- Disease may remain localized in the lungs or disseminate to other tissues, particularly the CNS, although the skin can also be affected.
- 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.
- Antigens to C. neoformans can be detected by latex agglutination.
- C. neoformans can be detected in approximately 60% of patients by india ink smear of CSF and cultured in more than 96% of patients.
- For asymptomatic, immunocompetent persons with isolated pulmonary disease and no evidence of CNS disease, careful observation may be warranted. With symptomatic infection, fluconazole or amphotericin B is warranted.
- 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.
- 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 2 or 3 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.
- Relapse of C. neoformans meningitis occurs in approximately 50% of AIDS patients after completion of primary therapy. Fluconazole (200 mg daily) is currently recommended for chronic suppressive therapy of cryptococcal meningitis in AIDS patients.