Cryptococcosis in an AIDS patient: itraconazole efficacy after other therapeutic failures.

Sir, Cryptococcus neoformans, an ubiquitous soil yeast, causes neurological and /or disseminated mycotic invasion and is the fourth most common infection in AIDS patients. ~ Conventional treatment of cryptococcosis [amphotericin B (AMB) with flucytosine] is not completely satisfactory in such patients because of persistent immune defects and frequent toxicity of these antifungal drugs. For these reasons fluconazole (FCZ) is often prescribed as initial therapy but it is effective in only about 40 % cases. 2 Itraconazole ( ITZ) , a recently introduced triazole, has been successfully administered after failure of the other drugs. We report the case of a 3o-year-old HIV-posi t ive man, who was hospitalised because of sudden coma and developed a left VI nerve paralysis a few days later. Cryptococcal meningitis was diagnosed when C. neoformans was isolated from the CSF and cryptococcal soluble antigen found in high titre in CSF and serum. Oral FCZ (400 rag/day) was prescribed with transient improvement of consciousness and the left VI nerve paralysis. However he then relapsed and developed bradypsychia and obnubilation. At the same time two low density cerebral lesions appeared on CT scan. On day 38 of treatment IV AMB (I mg/kg) was added and the FCZ raised to 800 mg/day. On day 55, neurological problems had increased and a further therapeutic change was implemented. Oral I T Z was prescribed in association with AMB for 7 days and then continued alone. In less than a week neurological improvement had started and the patient eventually achieved an approximately normal life style. After 9 months of I T Z administration, the patient was tolerating the drug satisfactorily apart from some disturbance of liver function tests (raised transaminase and alkaline phosphatase values) which required reduction of the dose to 200 mg/day. The response of our patient to I T Z following the therapeutic failure of FCZ and AMB in high dosage for 55 days, confirms its efficacy. There are however very few publications concerning I T Z therapy in AIDS cryptococcosisfl -~ Our case showed apparent clinical synergy between AMB and ITZ. In a previous study, I T Z alone had a 40 % complete response rate which rose to 83 % if up to I week of AMB was given before the ITZ . From a mycological point of view, CSF cultures were negative after 50 days of treatment, but after 7 months, direct examination confirmed the presence of cryptococcus and soluble antigen in the CSF. These findings did not reflect the clinical situation and justified continued I T Z therapy.