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Role of Rifampin in Reducing Inflammation and Neuronal Damage in Childhood Bacterial Meningitis: A Pilot Randomized Controlled Trial

Uppal, Lipi MD*; Singhi, Sunit MD*; Singhi, Pratibha MD*; Aggarwal, Ritu MD

The Pediatric Infectious Disease Journal: June 2017 - Volume 36 - Issue 6 - p 556–559
doi: 10.1097/INF.0000000000001513
Original Studies

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.

From the *Department of Pediatrics, and Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Accepted for publication November 8, 2016.

This study was approved by Institute Ethics Committee.

The authors have no funding or conflicts of interest to disclose.

Address for correspondence: Sunit Singhi, MD, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India-160012. E-mail: sunit.singhi@gmail.com.

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