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

Katherine M. Gaskell*, Camilla Rothe, Roshina Gnanadurai, Patrick Goodson, Chikondi Jassi, Robert S. Heyderman, Theresa J. Allain, Thomas S. Harrison, David G. Lalloo, Derek J. Sloan, Nicholas A. Feasey

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Objective: We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800mg oral fluconazole (57% [33/58]). National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200mg. 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 1200mg/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 800mg/day.

Results: 47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200mg, ten-week mortality remained 55% (26/47). This was no better than our previous study (Hazard Ratio [HR] of death on 1200mg vs. 800mg 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.

Original languageEnglish
Article numbere110285
Number of pages4
JournalPLoS One
Volume9
Issue number11
DOIs
Publication statusPublished - 6 Nov 2014

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