Role of Rifampin in Reducing Inflammation and Neuronal Damage in Childhood Bacterial Meningitis

Abstract

BACKGROUND: Treatment of acute bacterial meningitis in children with bactericidal antibiotics causes cell wall lysis and a surge in inflammatory cascade, which in turn contributes to neuronal damage and morbidity. Pretreatment with a nonbacteriolytic antibiotic, such as rifampin, has been shown to attenuate the inflammatory response in experimental models of bacterial meningitis. In a pilot study, in children with bacterial meningitis, we have studied markers of inflammatory response and neuronal damage in 2 groups of children with bacterial meningitis; one group received rifampin pretreatment with ceftriaxone and the other group received ceftriaxone alone. PATIENTS AND METHODS: Forty children with bacterial meningitis, who were 3 months to 12 years of age, were randomly assigned to receive either a single dose rifampin (20 mg/kg) 30 minutes before ceftriaxone or ceftriaxone alone was given. The primary outcome variables were cerebrospinal fluid (CSF) concentrations of tumor necrosis factor alpha (TNFα), S100B and neuron-specific enolase on day 1 and day 5, and secondary outcome variables were the values of TNFα and interleukin 6 in serum on day 1 and day 5; hearing and neurologic sequelae at 3 months after recovery from the illness. RESULTS: Children in rifampin pretreatment group had significantly lower CSF TNFα concentrations [median (interquartile range [IQR]): 15.5 (7.2-22.0) vs. 53.0 (9.0-87.5) pg/mL, P = 0.019] and S100B [median (IQR): 145.0 (54.7-450.0) vs. 447.5 (221.0-804.6) pg/mL, P = 0.033] on day 1 and S100B [median (IQR): 109.7 (64.0-287.0) vs. 322 (106.7-578.0) pg/mL, P = 0.048] and neuron-specific enolase [median (IQR): 8.6 (5-14.75) vs. 18.2 (7.0-28.75) ng/mL, P = 0.035] on day 5 when compared with ceftriaxone alone group. The rifampin-treated group also had reduced morbidity and neurologic sequelae; however, these were not statistically significant. CONCLUSIONS: Pretreatment with single dose rifampin 30 minutes before ceftriaxone administration reduced the CSF concentrations of markers of inflammation and neuronal damage in children with bacterial meningitis.