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.
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