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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, Feasey NA - PLoS ONE (2014)

Bottom Line: We assessed whether this has improved outcomes.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. 47 participants received fluconazole monotherapy.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)).

View Article: PubMed Central - PubMed

Affiliation: Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Liverpool School of Tropical Medicine, 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, 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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Related in: MedlinePlus

Kaplan-Meier Survival plot of patients on fluconazole.A: 800mg induction dose. B: Kaplan-Meier Survival plot of patients on fluconazole 1200mg induction dose.
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pone-0110285-g001: Kaplan-Meier Survival plot of patients on fluconazole.A: 800mg induction dose. B: Kaplan-Meier Survival plot of patients on fluconazole 1200mg induction dose.

Mentions: Mortality at 10 weeks was 55% (26/47). The median time to death was 16 days (IQR: 7–49 days). In the previous cohort, mortality at 10 weeks amongst patients who received fluconazole 800mg/day was 57% (33/58) and median time to death was 19 days (IQR: 6–61 days). Figure 1 shows Kaplan-Meier survival plots for patients initiated on fluconazole 800mg (1A) and fluconazole 1200mg (1B); there is no difference in survival between the two induction doses. The HR for death on 1200mg vs. 800mg was 1.29 (95% CI: 0.77–2.16, p = 0.332).


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, Feasey NA - PLoS ONE (2014)

Kaplan-Meier Survival plot of patients on fluconazole.A: 800mg induction dose. B: Kaplan-Meier Survival plot of patients on fluconazole 1200mg induction dose.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222805&req=5

pone-0110285-g001: Kaplan-Meier Survival plot of patients on fluconazole.A: 800mg induction dose. B: Kaplan-Meier Survival plot of patients on fluconazole 1200mg induction dose.
Mentions: Mortality at 10 weeks was 55% (26/47). The median time to death was 16 days (IQR: 7–49 days). In the previous cohort, mortality at 10 weeks amongst patients who received fluconazole 800mg/day was 57% (33/58) and median time to death was 19 days (IQR: 6–61 days). Figure 1 shows Kaplan-Meier survival plots for patients initiated on fluconazole 800mg (1A) and fluconazole 1200mg (1B); there is no difference in survival between the two induction doses. The HR for death on 1200mg vs. 800mg was 1.29 (95% CI: 0.77–2.16, p = 0.332).

Bottom Line: We assessed whether this has improved outcomes.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. 47 participants received fluconazole monotherapy.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)).

View Article: PubMed Central - PubMed

Affiliation: Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Liverpool School of Tropical Medicine, 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, 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.

Show MeSH
Related in: MedlinePlus