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Hemophilus influenzae Type b Meningitis in Infant Rabbits: Pathogenesis and Therapy

Hemophilus influenzae Type b Meningitis in Infant Rabbits: Pathogenesis and Therapy Abstract • A model of human Hemophilus influenzae type b meningitis was developed in infant rabbits infected intranasally. The pathogenesis and course resembled that in human beings; bacteremia was followed by meningitis with a high mortality. Pretreatment of the nasopharyngeal mucosa with 0.5% trypsin or normal saline significantly increased the rate of bacteremia. Death was age related. Intranasal challenge with type f and nontypeable H influenzae was associated with transient bacteremia. Our results suggest that factors on the respiratory tract epithelial cell surface influence colonization and infection with H influenzae type b and confirm the importance of other host and parasite factors. Intravenous aztreonam resulted in a peak CSF concentration that was 6% to 7% of the serum concentration in infected meninges but only 2% to 3% in normal meninges. Aztreonam reduced mortality in established H influenzae type b meningitis from 88% in untreated animals to 9%. (AJDC 1984;138:455-458) References 1. Prevention of secondary cases of Haemophilus influenzae type b disease . MMWR 1982; 31:672-680. 2. Sell SHW, Merrill RE, Doyne EO, et al: Long-term sequelae of Haemophilus influenzae meningitis . Pediatrics 1972;49:206-211. 3. San Joaquin VH, Altshuler GP, Robinson W, et al: Haemophilus influenzae b bacteremia and meningitis in infant rabbits following intranasal inoculation . J Lab Clin Med 1983;102:939-946. 4. Marks MI, Ziegler EJ, Douglas H, et al: Lethal Haemophilus influenzae type b infection in mice . Infection 1982;10:261-266.Crossref 5. Swabb EA, Leitz MA, Piekiewicz FG, et al: Pharmacokinetics of the monobactam SQ26776 after single intravenous doses in healthy subjects . J Antimicrob Chemother 1981;8:131-140.Crossref 6. Ostrow PT, Moxon ER, Vernon N, et al: Pathogenesis of bacterial meningitis: Studies of the route of meningeal invasion following Haemophilus influenzae inoculation of infant rats . Lab Invest 1979;40:678-685. 7. Moxon ER, Smith AL, Averill DR, et al: Haemophilus influenzae meningitis in infant rats after intranasal inoculation . J Infect Dis 1974;129:154-162.Crossref 8. Bacterial meningitis and meningococcemia—United States 1978 . MMWR 1979;28: 277-279. 9. Schneerson R, Robbins JB: Age-related susceptibility to Haemophilus influenzae type b disease in rabbits . Infect Immun 1971;4:397-401. 10. Greene GR: Meningitis due to Haemophilus influenzae other than type b: Case report and review . Pediatrics 1978;62:1021-1025. 11. Weller PF, Smith AL, Anderson P, et al: The role of encapsulation and host age in the clearance of Haemophilus influenzae bacteremia . J Infect Dis 1977;135:34-41.Crossref 12. Moxon ER, Vaughn KA: The type b capsular polysaccharide as a virulence determinant of Haemophilus influenzae: Studies using clinical isolates and laboratory transformants . J Infect Dis 1981;143:517-524.Crossref 13. Loeb MR, Smith DH: Outer membrane protein composition in disease isolates of Haemophilus influenzae: Pathogenic and epidemiological implications . Infect Immun 1980;30: 709-717. 14. Barenkamp SJ, Munson RS Jr, Granoff DM: Subtyping isolates of Haemophilus influenzae type b by outer-membrane protein profiles . J Infect Dis 1981;143:668-676.Crossref 15. Beachey EH: Bacterial adherence: Adhesin-receptor interactions mediating the attachment of bacteria to mucosal surfaces . J Infect Dis 1981;143:325-345.Crossref 16. Johanson WG Jr, Woods DE, Chaudhuri T: Association of respiratory tract colonization with adherence of gram-negative bacilli to epithelial cells . J Infect Dis 1979;139:667-673.Crossref 17. Williams RC, Gibbons RJ: Inhibition of streptococcal attachment to receptors on human buccal epithelium by antigenically similar salivary glycoproteins . Infect Immun 1975;11: 711-718. 18. Sakata Y, Boccazzi A, McCracken GH Jr: Pharmacokinetics and bacteriological effect of ceftazidime in experimental Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli meningitis . Antimicrob Agents Chemother 1983;23:213-217.Crossref 19. Scheld WM, Brodeur JP: Comparative activity of aztreonam in experimental meningitis, abstract 135. Program and abstracts of the 22nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Miami Beach, Oct 4-6, 1982. 20. Kobasa WD, Kaye D: Aztreonam, cefoperazone, and gentamicin in the treatment of experimental Enterobacter aerogenes endocarditis in rabbits . Antimicrob Agents Chemother 1983;24:321-324.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Diseases of Children American Medical Association

Hemophilus influenzae Type b Meningitis in Infant Rabbits: Pathogenesis and Therapy

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References (20)

Publisher
American Medical Association
Copyright
Copyright © 1984 American Medical Association. All Rights Reserved.
ISSN
0002-922X
DOI
10.1001/archpedi.1984.02140430033009
Publisher site
See Article on Publisher Site

Abstract

Abstract • A model of human Hemophilus influenzae type b meningitis was developed in infant rabbits infected intranasally. The pathogenesis and course resembled that in human beings; bacteremia was followed by meningitis with a high mortality. Pretreatment of the nasopharyngeal mucosa with 0.5% trypsin or normal saline significantly increased the rate of bacteremia. Death was age related. Intranasal challenge with type f and nontypeable H influenzae was associated with transient bacteremia. Our results suggest that factors on the respiratory tract epithelial cell surface influence colonization and infection with H influenzae type b and confirm the importance of other host and parasite factors. Intravenous aztreonam resulted in a peak CSF concentration that was 6% to 7% of the serum concentration in infected meninges but only 2% to 3% in normal meninges. Aztreonam reduced mortality in established H influenzae type b meningitis from 88% in untreated animals to 9%. (AJDC 1984;138:455-458) References 1. Prevention of secondary cases of Haemophilus influenzae type b disease . MMWR 1982; 31:672-680. 2. Sell SHW, Merrill RE, Doyne EO, et al: Long-term sequelae of Haemophilus influenzae meningitis . Pediatrics 1972;49:206-211. 3. San Joaquin VH, Altshuler GP, Robinson W, et al: Haemophilus influenzae b bacteremia and meningitis in infant rabbits following intranasal inoculation . J Lab Clin Med 1983;102:939-946. 4. Marks MI, Ziegler EJ, Douglas H, et al: Lethal Haemophilus influenzae type b infection in mice . Infection 1982;10:261-266.Crossref 5. Swabb EA, Leitz MA, Piekiewicz FG, et al: Pharmacokinetics of the monobactam SQ26776 after single intravenous doses in healthy subjects . J Antimicrob Chemother 1981;8:131-140.Crossref 6. Ostrow PT, Moxon ER, Vernon N, et al: Pathogenesis of bacterial meningitis: Studies of the route of meningeal invasion following Haemophilus influenzae inoculation of infant rats . Lab Invest 1979;40:678-685. 7. Moxon ER, Smith AL, Averill DR, et al: Haemophilus influenzae meningitis in infant rats after intranasal inoculation . J Infect Dis 1974;129:154-162.Crossref 8. Bacterial meningitis and meningococcemia—United States 1978 . MMWR 1979;28: 277-279. 9. Schneerson R, Robbins JB: Age-related susceptibility to Haemophilus influenzae type b disease in rabbits . Infect Immun 1971;4:397-401. 10. Greene GR: Meningitis due to Haemophilus influenzae other than type b: Case report and review . Pediatrics 1978;62:1021-1025. 11. Weller PF, Smith AL, Anderson P, et al: The role of encapsulation and host age in the clearance of Haemophilus influenzae bacteremia . J Infect Dis 1977;135:34-41.Crossref 12. Moxon ER, Vaughn KA: The type b capsular polysaccharide as a virulence determinant of Haemophilus influenzae: Studies using clinical isolates and laboratory transformants . J Infect Dis 1981;143:517-524.Crossref 13. Loeb MR, Smith DH: Outer membrane protein composition in disease isolates of Haemophilus influenzae: Pathogenic and epidemiological implications . Infect Immun 1980;30: 709-717. 14. Barenkamp SJ, Munson RS Jr, Granoff DM: Subtyping isolates of Haemophilus influenzae type b by outer-membrane protein profiles . J Infect Dis 1981;143:668-676.Crossref 15. Beachey EH: Bacterial adherence: Adhesin-receptor interactions mediating the attachment of bacteria to mucosal surfaces . J Infect Dis 1981;143:325-345.Crossref 16. Johanson WG Jr, Woods DE, Chaudhuri T: Association of respiratory tract colonization with adherence of gram-negative bacilli to epithelial cells . J Infect Dis 1979;139:667-673.Crossref 17. Williams RC, Gibbons RJ: Inhibition of streptococcal attachment to receptors on human buccal epithelium by antigenically similar salivary glycoproteins . Infect Immun 1975;11: 711-718. 18. Sakata Y, Boccazzi A, McCracken GH Jr: Pharmacokinetics and bacteriological effect of ceftazidime in experimental Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli meningitis . Antimicrob Agents Chemother 1983;23:213-217.Crossref 19. Scheld WM, Brodeur JP: Comparative activity of aztreonam in experimental meningitis, abstract 135. Program and abstracts of the 22nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Miami Beach, Oct 4-6, 1982. 20. Kobasa WD, Kaye D: Aztreonam, cefoperazone, and gentamicin in the treatment of experimental Enterobacter aerogenes endocarditis in rabbits . Antimicrob Agents Chemother 1983;24:321-324.Crossref

Journal

American Journal of Diseases of ChildrenAmerican Medical Association

Published: May 1, 1984

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