Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.632134
Title: Glycerol adjuvant therapy in adult bacterial meningitis in Malawi
Author: Ajdukiewicz, Katherine M. B.
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2012
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Abstract:
Background: Southern Africa has a high incidence of bacterial meningitis in adults, often associated with HN 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 In addition, we aimed to measure the effect of glycerol on reducing intracranial pressure and deafness. 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 50, 75, 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; reduction in cerebrospinal fluid opening pressure and optic nerve sheath diameter measurement at Day 2 and hearing loss at Day 40. 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 ISRClN70121840. 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 wa.s 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. Optic nerve sheath diameter and CSF opening pressure were not reduced by glycerol. There was a trend towards less hearing loss at Day 40 in the glycerol arm five (5.6%) compared with placebo 16 (21.3%) (p=0.026). 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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.632134  DOI: Not available
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