Multi-drug-resistant cryptococcal meningitis in an AIDS patient

Recurrent infection with Cryplococcus neoformans in HIV-infected individuals is generally due to relapse rather than reinfection or antifungal drug resistance. We report a patient with AIDS and multiple clinical relapses of cryptococcal meningitis due to progressive antrrungal drug resistance. CASE: 41-year-old Korean-American man found HIV+ in 2/95 with initial CD4 count of 72 cells/mm³. 2/95 asymptomatic; serum cryptococcal antigen (CA) 1:40%; given 400mg/d fluconazole (fluco) × 12 wks. 9/95 symptomatic cryptococcal meningitis; enrolled in amphotericin B (AmB) vs. liposomal AmB study, followed by fluco 400mg/d maintenance. 4/96 sx's recurred; given 500mg AmB plus 5-flucytosine (5FC) 500mg qid, followed by fluco 600mg/d maintenance. 8/96 right hermparesis, given AmB, followed by fluco 800mg/d plus 5FC maintenance; hemiparesis resolved 1/97 merungismus; given 500mg AmB followed by AmB 50mg qMWF plus fluco 800mg/d and 5FC. 3/97 severe pain radiating from posterior head down spine, nausea & vomiting unrelieved by lumbar puncture; died 3/29/97 (no autopsy was performed). The same strain of Cryptococcus neoformans was repeatedly isolated as determined by rep-PCR. E-test MICs (72-hr reeling) for C. neoformns isolated from CSF (μt/ml): Date Ampho B fluconazole itraconazole 5-FC CSF CA 9/08/95 0.25 24 0.50 >32 1:16,384 4/16/96 0.38 >256 0.50 >32 1:2048 8/16/96 0.50 >256 0.50 >32 1:512 3/10/97 1.00 >256 1.50 >32 1:1024 CONCLUSION: Progressive AIDS-related cryptococcal disease unresponsive to conventional therapy can occur due to progressive antifungal drug resistance.