Rifampin reduces early mortality in experimental Streptococcus pneumoniae meningitis

Compared with beta-lactam antibiotics,rifampin releases smaller quantities of proinflammatory cell wall products from Streptococcus pneumoniae in vitr o. Mice infected intracerebrally with S. pneumoniae were treated subcutaneo usly with 2-mg doses of rifampin or ceftriaxone (n = 43 each) every 12 h fo r 3 days and then observed for another 3 days. Rifampin reduced overall mor tality from 49% to 26% (P = .04). Kaplan-Meyer analysis revealed a substant ial reduction of mortality during the first 24 h in mice receiving rifampin (difference in survival time: P = .007). Eight h after receiving a single 2-mg dose of rifampin or ceftriaxone, rifampin-treated mice had lower serum and cerebrospinal fluid concentrations of lipoteichoic and teichoic acids than did ceftriaxone-treated mice (median serum level: <0.5 vs, 27.0 ng/mL, P = .02; median cerebrospinal fluid level of pooled specimens: 97.5 vs. 20 6.0 ng/mL), Thus, the use of rifampin appears promising for reducing the re lease of proinflammatory bacterial components and decreasing early mortalit y in bacterial meningitis.