A Prospective Study of Mortality from Cryptococcal Meningitis following Treatment Induction with 1200mg Oral Fluconazole in Blantyre, Malawi

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

来源：PLos One, 2014, 9(11): e110285.

DOI：10.1371/journal.pone.0110285

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.

• 出版日期2014-11-6