Cerebrospinal Fluid Endotoxin Levels in Children with H. influenzae Meningitis before and after Administration of Intravenous Ceftriaxone

Abstract

Total, cell-free,and cell-bound endotoxin and bacterial density weremeasured in cerebrospinal fluid (CSF) of 22 children with Hemophilus influenzae meningitis. Also the effect of ceftriaxone on CSF endotoxin levels was investigated in eight patients by reexamining their CSF 2–6 h after the initial dose. Initial CSF bacterial density correlated with initial CSF endotoxin levels (P < .001). Ceftriaxone induced a marked increase of free endotoxin in CSF, from an initial (mean ± SE) 0.75 ± 0.21 to 1.29 ± 0.23log₁₀ ng/ml (P < .01). This increase correlated positively with the number of bacteria killed in the CSF (P < .01). The increase in free endotoxin was associated with an increase in mean CSF lactate levels from 8.5 to 9.7 units/l (P < .05) and mean lactate dehydrogenase levels from 102 to 180mmol/l (P < .02)and a decrease in mean CSF glucose from 1.17 to 0.46 mmol/l (P < .05). Initial CSF total endotoxin concentrations correlated both with the HersonTodd clinical severity score (P < .001) and with the number of febrile hospital days (P < .001). These findings suggest that highly bactericidal agents initially lead to release of free endotoxin from gram-negative organisms into CSF, with associated enhanced inflammatory response by the host.