Amphotericin B is the treatment of choice for cryptococcal infection. 5-flucytosine may be added to amphotericin B for the first phase of treatment. Fluconazole has been used to treat meningitis in other patient populations but is not well studied in transplant recipients.

The total duration of treatment for cryptococcosis is a minimum of eight to ten weeks. Meningitis is initially treated with amphotericin B for the first two weeks followed by fluconazole for the remainder of therapy. Important adjunctive measures include repeated lumbar punctures to relieve elevated intracranial pressure, repeat analysis of CSF to monitor response to therapy, and periodic monitoring of the serum cryptococcal antigen to detect relapses.

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