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Pathophysiology of Citrobacter diversus neonatal meningitis: comparative studies in an infant mouse model
A L Soriano1, R G Russell, D Johnson
1Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201.
Abstract:
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 greater than 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.
Insights
Citrobacter diversus causes neonatal meningitis and brain abscesses. An infant mouse model showed age-related susceptibility and linked mortality to bacteremia, but strain-specific virulence factors remain unknown.
Area of Science:
- * Microbiology
- * Pathophysiology
- * Neonatal Infections
Background:
- * Citrobacter diversus is a significant cause of neonatal meningitis.
- * Infections are characterized by the formation of multiple brain abscesses.
- * Understanding the pathophysiology of these infections is crucial for developing effective treatments.
Purpose of the Study:
- * To develop and utilize an infant mouse intracranial inoculation model.
- * To evaluate the pathophysiology of Citrobacter diversus neonatal infections.
- * To identify factors correlating with mortality and disease severity.
Main Methods:
- * Intracranial inoculation of 2-day-old mice with Citrobacter diversus strains.
- * Assessment of mortality rates and correlation with strain characteristics and bacteremia.
- * Histopathological examination of brain lesions and evaluation of age-related susceptibility.
Main Results:
- * High mortality (>50%) observed in 2-day-old mice inoculated with 18 of 26 C. diversus strains.
- * Mortality significantly correlated with bacteremia, irrespective of the isolate's origin (CNS or non-CNS).
- * Characteristic brain lesions included suppurative ventriculitis and periventricular abscessation; younger mice (5-8 days old) showed reduced susceptibility.
Conclusions:
- * Citrobacter diversus demonstrates a propensity for causing brain abscesses in neonatal mice.
- * Bacteremia is a key factor associated with mortality in this model.
- * Age-related resistance to infection and CNS damage was observed, highlighting developmental factors in susceptibility.