A 35-year-old man (body weight = 63 kg) with AIDS complaining fever and headache after having commenced anti-retroviral therapy (ART) for a week was admitted to our hospital. Five lumbar punctures performed during 38 days could not confirm a cryptococcal meningitis (CM) based on staining or culture methods for cerebrospinal fluid (CSF). The disease quickly progressed with serious hearing/vision impairment and frequent onset of seizure and coma after being treated with corticosteroids for five days, and then CM was confirmed. Subsequent lumbar puncture showed elevated intracranial pressure as high as 870 mm H2O, even though treated with standard antifungal regimens for CM. His disease was finally controlled by a new triple therapy with amphotericin B (0.7 mg•kg-1•day-1, intravenously), flucytosine (100 mg/kg perday, orally in four divided doses), and voriconazole (200 mg every 12 hours) and ART containing lamivudine (300 mg/day), stavuding (30 mg, twice a day) and efavirenz (300 mg, orally every night). Although it is rare, negative CSF stain or culture for cryptococci in AIDS patients with CM can persist for a long time. Corticosteroids should be used cautiously when an effective anti-fungal therapy is not administered. Triple therapy with amphotericin B, flucytosine and voriconazole may be selectively applied in severe CM. Voriconazole can be co-administered with efavirenz with modified dosing
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