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Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial

Ajdukiewicz, Katherine, Cartwright, Katharine, Scarborough, Matthew, Mwambene, James, Goodson, Patrick, Molyneux, Malcolm E, Zijlstra, Eduard, French, Neil, Whitty, Christopher and Lalloo, David ORCID: https://orcid.org/0000-0001-7680-2200 (2011) 'Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial'. Lancet Infectious Diseases, Vol 11, Issue 4, pp. 293-300.

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Abstract

Background
Southern Africa has a high incidence of bacterial meningitis in adults, often associated with HIV co-infection. Mortality exceeds 50%, even with appropriate antibiotic therapy, and is not improved with corticosteroids. Glycerol adjuvant therapy reduces long-term morbidity in bacterial meningitis in children, and its use is being promoted. We aimed to assess the effectiveness of glycerol as an adjuvant therapy for adults with bacterial meningitis in Africa.

Methods
The study was done in two phases. First, in an open-label dose-finding study, 45 adult patients with symptoms, signs, and cerebrospinal fluid findings consistent with bacterial meningitis received either 50 mL, 75 mL, or 100 mL of glycerol four times a day for 4 days. We then did a randomised, double-blind, placebo-controlled trial of oral glycerol in adults with bacterial meningitis. Patients with clinical and cerebrospinal fluid findings suggestive of bacterial meningitis were randomly assigned in blocks of 12 by use of a random number list produced by an independent statistician to receive either glycerol or an equivalent volume of sugar solution. Glycerol and placebo were indistinguishable by colour or taste. The primary outcome was mortality at 40 days, with secondary outcomes including disability and mortality restricted to pneumococcal disease. All patients were analysed for the primary outcome excluding those who were lost to follow-up. This trial is registered at controlled-trials.com, number ISRCTN70121840.

Findings
75 mL glycerol four times a day was the highest tolerated dose, and was used for the main study. 265 patients were assigned treatment: 137 glycerol and 128 placebo. The trial was stopped early on the advice of the data and safety monitoring board after a planned interim analysis. By day 40, 61 (49%) of 125 patients in the placebo group and 86 (63%) of 136 in the glycerol group had died (adjusted odds ratio 2·4, 95% CI 1·3–4·2, p=0·003). There was no benefit from glycerol for death and disability by day 40, and glycerol did not improve death and disability by day 40 or death at day 40 in patients with proven bacterial disease or pneumococcal disease. Two serious adverse events occurred that were possibly due to the study drug.

Interpretation
Oral glycerol therapy cannot be recommended as an adjuvant therapy in adults with bacterial meningitis in resource-poor settings with a high HIV prevalence.

Funding
Meningitis Research Foundation.

Item Type: Article
Subjects: 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
Digital Object Identifer (DOI): https://doi.org/10.1016/S1473-3099(10)70317-0
Depositing User: Users 379 not found.
Date Deposited: 11 Sep 2012 11:09
Last Modified: 18 May 2018 14:17
URI: https://archive.lstmed.ac.uk/id/eprint/3029

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