title: Pneumococcal meningitis: development of a new animal model.
abstract: OBJECTIVE
  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 x 10 and 1 x 10 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 x 10 CFU i.p., 3 x 10 CFU middle ear, and 1 x 10 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Bionic Ear Institute, Department of Otolaryngology, University of Melbourne, Royal Victorian Eye & Ear Hospital, Melbourne, Victoria, Australia. bwei@bionicear.org
authors.forename: Benjamin P C
authors.initials: BP
authors.lastname: Wei
authors.forename: Robert K
authors.initials: RK
authors.lastname: Shepherd
authors.forename: Roy M
authors.initials: RM
authors.lastname: Robins-Browne
authors.forename: Graeme M
authors.initials: GM
authors.lastname: Clark
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Leary
mesh_terms: D000818:Animals; D002555:Cerebrospinal Fluid / Q000382:microbiology; D019929:Cochlear Implantation / Q000009:adverse effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D006319:Hearing Loss, Sensorineural / Q000382:microbiology; D008586:Meningitis, Pneumococcal / Q000209:etiology* / Q000382:microbiology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*