Rifampin Reduces Production of Reactive Oxygen Species of Cerebrospinal Fluid Phagocytes and Hippocampal Neuronal Apoptosis in ExperimentalStreptococcus pneumoniaeMeningitis

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Abstract
Bacterial compounds induce the production of reactive oxygen species (ROS) in meningitis. Rifampin releases smaller quantities of proinflammatory compounds from Streptococcus pneumoniae than do β-lactam antibiotics. Therefore, rabbits infected intracisternally with S. pneumoniae were treated intravenously either with rifampin 5 mg/kg/h or ceftriaxone 10 mg/kg/h (n = 9 each). Before initiation of antibiotic treatment, a strong positive correlation between ROS production of cerebrospinal fluid (CSF) phagocyte populations and bacterial CSF titers was observed (granulocytes: rs = .90, P < .0001; monocytes: rs = .81, P < .0001). CSF leukocytes from rifampin-treated rabbits produced less ROS (monocytes at 2 h after initiation of treatment: P = .045; at 5h: P = .014; granulocytes at 5h: P = .036) than did leukocytes from animals receiving ceftriaxone. The CSF malondialdehyde concentrations and the density of apoptotic neurons in the dentate gyrus were lower in rifampin- than in ceftriaxone-treated animals (P = .002 and .005). The use of rifampin to reduce the release of ROS and to decrease secondary brain injury appears promising.

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