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

• Published in: PloS one Vol. 9; no. 11; p. e110285
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science (PLoS) 2014
• Subjects: Adult; AIDS-Related Opportunistic Infections - drug therapy; AIDS-Related Opportunistic Infections - mortality; Antifungal Agents - therapeutic use; Female; Fluconazole - therapeutic use; HIV-1; Humans; Malawi - epidemiology; Male; Meningitis, Cryptococcal - drug therapy; Meningitis, Cryptococcal - mortality; Prospective Studies; Treatment Outcome; Malawi
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0110285

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