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Pneumococcal Meningitis: Development of a New Animal Model

Wei, Benjamin P. C.*†; Shepherd, Robert K.*†; Robins-Browne, Roy M.; Clark, Graeme M.*; O'Leary, Stephen J.*†

doi: 10.1097/01.mao.0000231603.25961.f1
Cochlear Implants

Hypothesis: The rat is a suitable animal to establish a model for the study of pneumococcal meningitis postcochlear implantation.

Background: There has been an increase in the number of cases of cochlear implant-related meningitis. The most common organism identified was Streptococcus pneumoniae. Whether cochlear implantation increases the risk of pneumococcal meningitis in healthy subjects without other risk factors remains to be determined. Previous animal studies do not focus on the pathogenesis and risk of pneumococcal meningitis postimplantation and are based on relatively small animal numbers, making it difficult to assess the cause-and-effect relationship. There is, therefore, a need to develop a new animal model allowing direct examination of the pathogenesis of meningitis in the presence of a cochlear implant.

Methods: Eighteen nonimplanted rats were infected with 1 × 106 and 1 × 108 colony-forming units (CFU) of a clinical isolate of S. pneumoniae via three different inoculation routes (middle ear, inner ear, and i.p.) to examine for evidence of meningitis during 24 hours. Six implanted rats were infected with the highest amount of bacteria possible for each route of inoculation (4 × 1010 CFU i.p., 3 × 108 CFU middle ear, and 1 × 106 CFU inner ear) to examine for evidence of meningitis with the presence of an implant. The histological pattern of cochlear infections for each of the three different inoculating routes were examined.

Results: Pneumococcal meningitis was evident in all 6 implanted animals for each of the three different routes of inoculation. Once in the inner ear, bacteria were found to enter the central nervous system via either the cochlear aqueduct or canaliculi perforantes of the osseous spiral lamina, reaching the perineural and perivascular space then the internal acoustic meatus. The rate, extent, and pattern of infection within the cochleae depended on the route of inoculation. Finally, there was no evidence of pneumococcal meningitis observed in 18 nonimplanted rats inoculated at a lower concentration of S. pneumoniae when observed for 24 hours postinoculation.

Conclusion: Meningitis in implanted rats after inoculation with a clinical isolate of S. pneumoniae is possible via all three potential routes of infection via the upper respiratory tract. The lack of meningitis observed in the 18 nonimplanted rats suggests that longer postinoculation monitoring periods are required to ensure whether or not meningitis will develop. Based on this work, we have developed a new animal model that will allow quantitative risk assessment of meningitis postcochlear implantation, and the assessment of the efficacy of potential interventional strategies in future studies.

*Bionic Ear Institute; and Departments of †Otolaryngology, and ‡Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia

Address correspondence and reprint requests to Dr. Benjamin P. C. Wei, The Bionic Ear Institute and Department of Otolaryngology, University of Melbourne, Royal Victorian Eye & Ear Hospital, 32 Gisborne Street, East Melbourne, 3002, Australia; E-mail:

This study was supported by The Garnett Passe and Rodney Williams Memorial Foundation Scholarship in Otolaryngology Head and Neck Surgery; The Wagstaff Fellowship, Royal Victorian Eye & Ear Hospital; National Institutes of Health-NIDCD-N01-DC-3-1005; and the Bionic Ear Institute.

© 2006 Otology & Neurotology, Inc.