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

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Gaskell, Katherine M., Rothe, Camilla, Gnanadurai, Roshina, Goodson, Patrick, Jassi, Chikondi, Heyderman, Robert, Allain, Theresa J., Harrison, Thomas S., Lalloo, David ORCID: https://orcid.org/0000-0001-7680-2200, Sloan, Derek and Feasey, Nicholas ORCID: https://orcid.org/0000-0003-4041-1405 (2014) 'A Prospective Study of Mortality from Cryptococcal Meningitis following Treatment Induction with 1200mg Oral Fluconazole in Blantyre, Malawi'. PLoS ONE, Vol 9, Issue 11, e110285.

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Abstract

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.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 252 Antifungal agents. Antifungal antibiotics
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.5 Complications
WL Nervous System > WL 200 Meninges. Blood-brain barrier
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pone.0110285
Depositing User: Lynn Roberts-Maloney
Date Deposited: 18 Mar 2015 15:15
Last Modified: 06 Feb 2018 13:09
URI: http://archive.lstmed.ac.uk/id/eprint/5022

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