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A prospective study of mortality from cryptococcal meningitis following treatment induction with 1200 mg oral fluconazole in Blantyre, Malawi.

Gaskell, KM; Rothe, C; Gnanadurai, R; Goodson, P; Jassi, C; Heyderman, RS; Allain, TJ; Harrison, TS; Lalloo, DG; Sloan, DJ; et al. Gaskell, KM; Rothe, C; Gnanadurai, R; Goodson, P; Jassi, C; Heyderman, RS; Allain, TJ; Harrison, TS; Lalloo, DG; Sloan, DJ; Feasey, NA (2014) A prospective study of mortality from cryptococcal meningitis following treatment induction with 1200 mg oral fluconazole in Blantyre, Malawi. PLoS One, 9 (11). ISSN 1932-6203 https://doi.org/10.1371/journal.pone.0110285
SGUL Authors: Harrison, Thomas Stephen

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Abstract

OBJECTIVE: We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800 mg oral fluconazole (57% [33/58]). National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200 mg. We assessed whether this has improved outcomes. DESIGN: This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200 mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800 mg/day. RESULTS: 47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200 mg, ten-week mortality remained 55% (26/47). This was no better than our previous study (Hazard Ratio [HR] of death on 1200 mg vs. 800 mg fluconazole: 1.29 (95% CI: 0.77-2.16, p = 0.332)). There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07-1.03, p = 0.055]). CONCLUSION: There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis.

Item Type: Article
Additional Information: ©2014 Gaskell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: General Science & Technology, MD Multidisciplinary
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: PLoS One
Article Number: e110285
ISSN: 1932-6203
Language: eng
Dates:
DateEvent
6 November 2014Published
PubMed ID: 25375145
Web of Science ID: WOS:000344402600009
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107288
Publisher's version: https://doi.org/10.1371/journal.pone.0110285

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