Intraventricular gentamicin therapy in gram-negative bacillary meningitis of infancy. Report of the Second Neonatal Meningitis Cooperative Study Group.
In a multicentre controlled trial in the U.S.A. and Latin America 52 infants with meningitis and ventriculitis were randomly assigned to receive either systemic ampicillin and gentamicin or intraventricular gentamicin plus systemic antimicrobial agents. The aetiological agents most often encountered were Escherichia coli in the U.S. infants and Salmonella spp. in Latin American infants. Infants receiving systemic antibiotics plus intraventricular gentamicin had a significantly higher mortality rate (42.9%) than those who received systemic therapy only (12.5%). Duration of positive CSF cultures and morbidity rates were not significantly different in the two treatment groups. The concentrations of gentamicin in ventricular and lumbar CSF 1--6 h after an intraventricular dose of 2.5 mg gentamicin were 10--130 microgram/ml and 8--85 microgram/ml, respectively. The study was terminated early because of the higher mortality rate in the intraventricular-therapy group. Intraventricular gentamicin should not be used as routine treatment for neonatal meningitis caused by gram-negative enteric bacilli.
In one trial that enrolled infants with gram-negative meningitis and ventriculitis, the use of intraventricular antibiotics in addition to intravenous antibiotics resulted in a three-fold increased RR for mortality compared to standard treatment with intravenous antibiotics alone. Based on this result, intraventricular antibiotics as tested in this trial should be avoided. Further trials comparing these interventions are not justified in this population.