Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1991 Apr;59(4):1352–1358. doi: 10.1128/iai.59.4.1352-1358.1991

Pathophysiology of Citrobacter diversus neonatal meningitis: comparative studies in an infant mouse model.

A L Soriano 1, R G Russell 1, D Johnson 1, R Lagos 1, I Sechter 1, J G Morris Jr 1
PMCID: PMC257850  PMID: 2004815

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.

Full text

PDF
1352

Images in this article

1355Image
on p.1355
1355Image
on p.1355
1355Image
on p.1355
1356Image
on p.1356
1356Image
on p.1356
1356Image
on p.1356

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altmann G., Sechter I., Braunstein I., Gerichter C. B. Citrobacter koseri isolated in Israel, 1972-83. Isr J Med Sci. 1984 Nov;20(11):1056–1060. [PubMed] [Google Scholar]
  2. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen Y., Nakane A., Minagawa T. Recombinant murine gamma interferon induces enhanced resistance to Listeria monocytogenes infection in neonatal mice. Infect Immun. 1989 Aug;57(8):2345–2349. doi: 10.1128/iai.57.8.2345-2349.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Christensen R. D., Rothstein G., Anstall H. B., Bybee B. Granulocyte transfusions in neonates with bacterial infection, neutropenia, and depletion of mature marrow neutrophils. Pediatrics. 1982 Jul;70(1):1–6. [PubMed] [Google Scholar]
  5. Curless R. G. Neonatal intracranial abscess: two cases caused by Citrobacter and a literature review. Ann Neurol. 1980 Sep;8(3):269–272. doi: 10.1002/ana.410080308. [DOI] [PubMed] [Google Scholar]
  6. Finne J. Occurrence of unique polysialosyl carbohydrate units in glycoproteins of developing brain. J Biol Chem. 1982 Oct 25;257(20):11966–11970. [PubMed] [Google Scholar]
  7. Foreman S. D., Smith E. E., Ryan N. J., Hogan G. R. Neonatal Citrobacter meningitis: pathogenesis of cerebral abscess formation. Ann Neurol. 1984 Dec;16(6):655–659. doi: 10.1002/ana.410160606. [DOI] [PubMed] [Google Scholar]
  8. Friede R. L. Cerebral infarcts complicating neonatal leptomeningitis. Acute and residual lesions. Acta Neuropathol. 1973 Feb 19;23(3):245–253. doi: 10.1007/BF00687879. [DOI] [PubMed] [Google Scholar]
  9. Glode M. P., Sutton A., Moxon E. R., Robbins J. B. Pathogenesis of neonatal Escherichia coli meningitis: induction of bacteremia and meningitis in infant rats fed E. coli K1. Infect Immun. 1977 Apr;16(1):75–80. doi: 10.1128/iai.16.1.75-80.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Graham D. R., Anderson R. L., Ariel F. E., Ehrenkranz N. J., Rowe B., Boer H. R., Dixon R. E. Epidemic nosocomial meningitis due to Citrobacter diversus in neonates. J Infect Dis. 1981 Sep;144(3):203–209. doi: 10.1093/infdis/144.3.203. [DOI] [PubMed] [Google Scholar]
  11. Graham D. R., Band J. D. Citrobacter diversus brain abscess and meningitis in neonates. JAMA. 1981 May 15;245(19):1923–1925. [PubMed] [Google Scholar]
  12. Gross R. J., Rowe B. Citrobacter koseri (syn. C. diversus): biotype, serogroup and drug resistance patterns of 517 strains. J Hyg (Lond) 1983 Apr;90(2):233–239. doi: 10.1017/s0022172400028904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gwynn C. M., George R. H. Neonatal citrobacter meningitis. Arch Dis Child. 1973 Jun;48(6):455–458. doi: 10.1136/adc.48.6.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hill H. R. Host defenses in the neonate: prospects for enhancement. Semin Perinatol. 1985 Jan;9(1):2–11. [PubMed] [Google Scholar]
  15. Kline M. W. Citrobacter meningitis and brain abscess in infancy: epidemiology, pathogenesis, and treatment. J Pediatr. 1988 Sep;113(3):430–434. doi: 10.1016/s0022-3476(88)80623-1. [DOI] [PubMed] [Google Scholar]
  16. Kline M. W., Kaplan S. L., Hawkins E. P., Mason E. O., Jr Pathogenesis of brain abscess formation in an infant rat model of Citrobacter diversus bacteremia and meningitis. J Infect Dis. 1988 Jan;157(1):106–112. doi: 10.1093/infdis/157.1.106. [DOI] [PubMed] [Google Scholar]
  17. Kline M. W., Mason E. O., Jr, Kaplan S. L. Characterization of Citrobacter diversus strains causing neonatal meningitis. J Infect Dis. 1988 Jan;157(1):101–105. doi: 10.1093/infdis/157.1.101. [DOI] [PubMed] [Google Scholar]
  18. Levy R. L., Saunders R. L. Citrobacter meningitis and cerebral abscess in early infancy: cure by moxalactam. Neurology. 1981 Dec;31(12):1575–1577. doi: 10.1212/wnl.31.12.1575. [DOI] [PubMed] [Google Scholar]
  19. Lin F. C., Devoe W. F., Morrison C., Libonati J., Powers P., Gross R. J., Rowe B., Israel E., Morris J. G., Jr Outbreak of neonatal Citrobacter diversus meningitis in a suburban hospital. Pediatr Infect Dis J. 1987 Jan;6(1):50–55. doi: 10.1097/00006454-198701000-00013. [DOI] [PubMed] [Google Scholar]
  20. McCracken G. H., Jr, Eichenwald H. F. Leukocyte function and the development of opsonic and complement activity in the neonate. Am J Dis Child. 1971 Feb;121(2):120–126. doi: 10.1001/archpedi.1971.02100130074008. [DOI] [PubMed] [Google Scholar]
  21. McDade R. L., Jr, Johnston K. H. Characterization of serologically dominant outer membrane proteins of Neisseria gonorrhoeae. J Bacteriol. 1980 Mar;141(3):1183–1191. doi: 10.1128/jb.141.3.1183-1191.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Morris J. G., Jr, Lin F. Y., Morrison C. B., Gross R. J., Khabbaz R., Maher K. O., Rowe B., Israel E., Libonati J. P. Molecular epidemiology of neonatal meningitis due to Citrobacter diversus: a study of isolates from hospitals in Maryland. J Infect Dis. 1986 Sep;154(3):409–414. doi: 10.1093/infdis/154.3.409. [DOI] [PubMed] [Google Scholar]
  23. Parkkinen J., Korhonen T. K., Pere A., Hacker J., Soinila S. Binding sites in the rat brain for Escherichia coli S fimbriae associated with neonatal meningitis. J Clin Invest. 1988 Mar;81(3):860–865. doi: 10.1172/JCI113395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ribeiro C. D., Davis P., Jones D. M. Citrobacter koseri meningitis in a special care baby unit. J Clin Pathol. 1976 Dec;29(12):1094–1096. doi: 10.1136/jcp.29.12.1094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Richard C., Brisou B., Lioult J. Etude taxonomique de "Levinea" nouveau genre de la famille des entérobactéries. Ann Inst Pasteur (Paris) 1972 Jun;122(6):1137–1146. [PubMed] [Google Scholar]
  26. Santos J. I., Shigeoka A. O., Rote N. S., Hill H. R. Protective efficacy of a modified immune serum globulin in experimental group B streptococcal infection. J Pediatr. 1981 Dec;99(6):873–879. doi: 10.1016/s0022-3476(81)80009-1. [DOI] [PubMed] [Google Scholar]
  27. Sears S. D., Richardson K., Young C., Parker C. D., Levine M. M. Evaluation of the human immune response to outer membrane proteins of Vibrio cholerae. Infect Immun. 1984 May;44(2):439–444. doi: 10.1128/iai.44.2.439-444.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Shortland-Webb W. R. Proteus and coliform meningoencephalitis in neonates. J Clin Pathol. 1968 Jul;21(4):422–431. doi: 10.1136/jcp.21.4.422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tacket C. O., Maneval D. R., Levine M. M. Purification, morphology, and genetics of a new fimbrial putative colonization factor of enterotoxigenic Escherichia coli O159:H4. Infect Immun. 1987 May;55(5):1063–1069. doi: 10.1128/iai.55.5.1063-1069.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vogel L. C., Ferguson L., Gotoff S. P. Citrobacter infections of the central nervous system in early infancy. J Pediatr. 1978 Jul;93(1):86–88. doi: 10.1016/s0022-3476(78)80611-8. [DOI] [PubMed] [Google Scholar]
  31. Williams W. W., Mariano J., Spurrier M., Donnell H. D., Jr, Breckenridge R. L., Jr, Anderson R. L., Wachsmuth I. K., Thornsberry C., Graham D. R., Thibeault D. W. Nosocomial meningitis due to Citrobacter diversus in neonates: new aspects of the epidemiology. J Infect Dis. 1984 Aug;150(2):229–235. doi: 10.1093/infdis/150.2.229. [DOI] [PubMed] [Google Scholar]
  32. Willis J., Robinson J. E. Enterobacter sakazakii meningitis in neonates. Pediatr Infect Dis J. 1988 Mar;7(3):196–199. doi: 10.1097/00006454-198803000-00012. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES