EXPERIMENTAL ESCHERICHIA COLI MENINGITIS IN NEWBORN SOS GUINEA PIGS

Abstract

Newborn albino guinea pigs (GP's) were used as an animal model for Gram negative neonatal meningitis (NM). Twenty-four GP's 4-5 days old were inoculated intranasally with 108-9 E. coli K1 organisms (MIC 0.1 ug/ml gentamicin) originally isolated from human NM. Bacteremia occurred in 50% of GP's within 48h, and meningitis (defined by positive CSF culture) was detected in 80% of bacteremic GP's within 5 days. Seven of 8 (88%) GP's with meningitis died within 7 days. All animals were sacrificed at 7 days post-inoculation and brains were examined histologically. There was 100% agreement between positive or negative CSF culture and presence or absence of inflammatory meningeal reaction. The majority (88%) of GP's with meningitis also had ventriculitis. Two further experiments revealed that the results (rate of bacteremia, positive CSF, mortality) were reproducible. A group of animals was also treated with gentamicin (2.5 mg/kg IM q12h) begun after diagnostic cisternal puncture at 16h post inoculation. Mean serum and CSF gentamicin levels were 3.6 and 0.16 ug/ml, respectively. Mortality in meningitic GP's was reduced by about 60% with gentamicin therapy. These results suggest that the newborn GP may be a useful model to study pathogenesis and efficacy of therapeutic agents in E. coli NM, since a) meningitis can be induced in a predictable and reproducible manner and b) the non-lethal sampling of CSF permits assessment of therapeutic responses and measurement of antibiotic levels.