PATHOPHYSIOLOGY OF CITROBACTER-DIVERSUS NEONATAL MENINGITIS - COMPARATIVE-STUDIES IN AN INFANT MOUSE MODEL

Citrobacter diversus is a cause of devastating neonatal meningitis, with illness characterized by formation of multiple brain abscesses. We developed an infant mouse intracranial inoculation model to evaluate the pathophysiology of C. diversus neonatal infections. Eighteen of 26 strains inoculated intracranially at a dose of ca. 3.3 x 10(3) CFU caused > 50% mortality in 2-day-old mice. No correlation was seen between the epidemiologic characteristics of a strain and its rate of mortality. When seven C. diversus isolates (four isolates from patients with meningitis, three from non-central nervous system [CNS] sites) were further evaluated, mortality was significantly correlated with bacteremia. The initial lesion in the CNS was a suppurative ventriculitis beginning 1 to 2 days postinoculation. Subsequent ventriculomegaly was associated with ventriculitis and periventricular abscessation. Brain lesions were seen with all strains, although strains of low virulence (as measured by having no bacteremia and low mortality) caused less-severe damage. An age-related susceptibility to C. diversus brain lesions was demonstrated, with 5-day-old mice showing a significant reduction in, and 8-day-old mice being apparently resistant to, infection and CNS damage. Our data indicate that C. diversus has a propensity to cause abscess formation in the neonatal mouse brain, with characteristic pathologic findings; however, the factors that determine whether a strain will cause meningitis in a human infant remain to be identified.