Adjunctive dexamethasone and 30-day all-cause death after hospital admission in paediatric pneumococcal meningitis: a propensity score analysis

Abstract

Background: Pneumococcal meningitis is a leading cause of bacterial meningitis and the most deadly pneumococcal disease in children worldwide. There is a paucity of evidence concerning the benefit of dexamethasone to prevent death in paediatric pneumococcal meningitis. We aimed to compare the effect of early adjunctive therapy with dexamethasone versus no dexamethasone on death in children with pneumococcal meningitis.

Methods: We did a non-randomised, comparative, multicentre, retrospective, quasi-experimental, propensity score-based study using data from a French national surveillance system of pneumococcal meningitis in children that collates data for 238 French paediatric wards working with 168 microbiology laboratories. We compared outcomes of adjunctive therapy with dexamethasone treatment (0·15 mg/kg every 6 h, for 4 days, per national guidelines) given within 12 h of antibiotic treatment versus no dexamethasone among all children aged 0-17 years with confirmed pneumococcal meningitis who had been hospitalised in one of the participating centres between Jan 1, 2005, and Nov 1, 2022. The primary outcome was 30-day all-cause death after hospital admission. The main propensity score analysis was based on inverse probability treatment weighting (IPTW), allowing adjustment for initial severity and baseline characteristics. Sensitivity analyses, such as propensity score matching, were done to assess the robustness of the results.

Findings: Between Jan 1, 2005, and Nov 1, 2022, 1765 cases of pneumococcal meningitis were reported to the National Surveillance System of Paediatric Bacterial Meningitis. 534 were excluded from the analysis and 1231 were included, with a median age of 1·1 years (IQR 0·5-5·0, range 0-17·9). 495 (40%) of 1231 patients were female, 716 (58%) were male, and 20 (1%) were missing data for sex. 650 (53%) of 1231 children received dexamethasone and 581 (47%) children did not receive dexamethasone. 108 (9%) of 1231 patients died. Within 30 days of hospitalisation, 105 (9%) patients died, 36 (6%) of 650 in the dexamethasone group and 69 (12%) of 581 in the no dexamethasone group. After IPTW, the adjusted 30-day death rate was 6% in the dexamethasone group and 12% in the no dexamethasone group (marginal odds ratio 0·39, 95% CI 0·23-0·65). All sensitivity analyses gave similar results.

Interpretation: Adjunctive dexamethasone within 12 h of starting antibiotic treatment was associated with a reduced 30-day risk of death in children hospitalised with pneumococcal meningitis. Our findings support the use of dexamethasone to reduce the risk of death in paediatric pneumococcal meningitis.

Funding: Pfizer, ACTIV, and National Institute of Health and Medical Research (Inserm) Centre.