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


METHODS
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]).


CONCLUSIONS
There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis.
Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Katherine M
KM
Gaskell
Department of Medicine, University of Malawi, College of Medicine, Blantyre, Malawi; Queen Elizabeth Central Hospital, Ministry of Health, Blantyre, Malawi.
Camilla
C
Rothe
Department of Medicine, University of Malawi, College of Medicine, Blantyre, Malawi; Queen Elizabeth Central Hospital, Ministry of Health, Blantyre, Malawi.
Roshina
R
Gnanadurai
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.
Patrick
P
Goodson
Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
Chikondi
C
Jassi
Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Robert S
RS
Heyderman
Department of Medicine, University of Malawi, College of Medicine, Blantyre, Malawi; Queen Elizabeth Central Hospital, Ministry of Health, Blantyre, Malawi.
Theresa J
TJ
Allain
Infection and Immunity Research Centre, St. George's Medical School, University of London, London, United Kingdom.
Thomas S
TS
Harrison
Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
David G
DG
Lalloo
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.
Derek J
DJ
Sloan
Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Nicholas A
NA
Feasey
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000401:mortality*; D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008295:Malawi / Q000453:epidemiology; D008297:Male; D016919:Meningitis, Cryptococcal / Q000188:drug therapy* / Q000401:mortality*; D011446:Prospective Studies; D016896:Treatment Outcome
D000935:Antifungal Agents; D015725:Fluconazole