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PLoS One. 2014 Nov 6;9(11):e110285. doi: 10.1371/journal.pone.0110285. eCollection 2014.

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

Author information

1
Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
2
Department of Medicine, University of Malawi, College of Medicine, Blantyre, Malawi; Queen Elizabeth Central Hospital, Ministry of Health, Blantyre, Malawi.
3
Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Department of Medicine, University of Malawi, College of Medicine, Blantyre, Malawi; Queen Elizabeth Central Hospital, Ministry of Health, Blantyre, Malawi.
4
Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
5
Infection and Immunity Research Centre, St. George's Medical School, University of London, London, United Kingdom.
6
Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.

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, pā€Š=ā€Š0.332)). 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, pā€Š=ā€Š0.055]).

CONCLUSION:

There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis.

PMID:
25375145
PMCID:
PMC4222805
DOI:
10.1371/journal.pone.0110285
[Indexed for MEDLINE]
Free PMC Article

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