Increased endotoxin and interleukin-1 beta concentrations in cerebrospinal fluid of infants with coliform meningitis and ventriculitis associated with intraventricular gentamicin therapy

Abstract

Intraventricular gentamicin therapy in infants with gram-negative enteric bacillary meningitis and ventriculitis is associated with increased mortality. Therefore, endotoxin, interleukin-1 beta, and cachectin (tumor necrosis factor) concentrations in ventricular cerebrospinal fluid from 21 infants (11 received intravenous antibiotics alone and 10 received intraventricular gentamicin also) were determined and correlated with outcome and other ventricular cerebrospinal fluid indexes of inflammation. Mean interleukin-1 beta concentrations in ventricular cerebrospinal fluid correlated significantly with adverse outcome and with mean concentrations of endotoxin, white blood cells, and protein and inversely with glucose concentrations. Mean and peak endotoxin and interleukin-1 beta concentrations were significantly higher in infants who received intraventricular gentamicin and intravenous antibiotics than in infants given intravenous antibiotics alone. Intraventricular gentamicin may have caused release of endotoxin from gram-negative bacilli in ventricular cerebrospinal fluid, resulting in increased interleukin-1 beta concentrations and inflammation, which could have contributed to the poor outcome in these patients.