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Open Access Highly Accessed Research article

Outcome of AIDS-associated cryptococcal meningitis initially treated with 200 mg/day or 400 mg/day of fluconazole

CF Schaars14, GA Meintjes1, C Morroni3, FA Post15 and G Maartens2*

Author Affiliations

1 Division of Infectious Diseases, University of Cape Town, Cape Town, South Africa

2 Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa

3 School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa

4 Canisius Wilhelmina Hospital, Nijmegen, The Netherlands

5 King's College London School of Medicine, London, UK

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BMC Infectious Diseases 2006, 6:118  doi:10.1186/1471-2334-6-118

Published: 18 July 2006

Abstract

Background

AIDS-associated cryptococcal meningitis has a high mortality. Fluconazole was the only systemic antifungal therapy available in our centre. From 1999–2001 we used low-dose fluconazole (200 mg daily initially), and did not offer therapy to patients perceived to have poor prognoses. In 2001 donated fluconazole became available, allowing us to use standard doses (400 mg daily initially). Antiretroviral therapy was not available during the study period.

Methods

Retrospective chart review of adult patients before and after the fluconazole donation.

Results

205 patients fulfilled the inclusion criteria, 77 before and 128 after the donation. Following the donation fewer patients received no antifungal treatment (5% vs 19%, p = 0.002), and more patients received standard-dose fluconazole (90% vs 6%, p < 0.001). In-hospital mortality was 25%. Impaired consciousness, no antifungal treatment received and cerebrospinal fluid antigen titre > 1,000 were independent predictors of in-hospital mortality. Concomitant rifampicin did not affect in-hospital survival. Thirteen patients were referred to the tertiary referral hospital and received initial treatment with amphotericin B for a mean of 6 days – their in-hospital survival was not different from patients who received only fluconazole (p = 0.9). Kaplan-Meier analysis showed no differences in length of survival by initial treatment with standard or low doses of fluconazole (p = 0.27 log rank test); median survival was 76 and 82 days respectively.

Conclusion

Outcome of AIDS-associated cryptococcal meningitis is similar with low or standard doses of fluconazole. The early mortality is high. Initial therapy with amphotericin B and other measures may be needed to improve outcome.