Pneumococcal Meningitis Threshold Model: A Potential Tool to Assess Infectious Risk of New or Existing Inner Ear Surgical Interventions

Hypothesis: A minimal threshold of Streptococcus pneumoniae is required to induce meningitis in healthy animals for intraperitoneal (hematogenous), middle ear, and inner ear inoculations, and this threshold may be altered via recent inner ear surgery. Background: There has been an increase in the number of reported cases of cochlear implant-related pneumococcal meningitis since 2002. The pathogenesis of pneumococcal meningitis is complex and not completely understood. The bacteria can reach the central nervous system (CNS) from the upper respiratory tract mucosa via either hematogenous route or via the inner ear. The establishment of a threshold model for all potential routes of infection to the CNS in animals without cochlear implantation is an important first step to help us understand the pathogenesis of the disease in animals with cochlear implantation. Methods: Fifty-four otologically normal adult Hooded Wistar rats (27 receiving cochleostomy and 27 controls) were inoculated with different amounts of bacterial counts via three different routes (intraperitoneal, middle ear, and inner ear). Rats were monitored during 5 days for signs of meningitis. Blood, cerebrospinal fluid, and middle ear swabs were taken for bacterial culture, and brains and cochleae were examined for signs of infection. Results: The threshold of bacterial counts required to induce meningitis is lowest in rats receiving direct inner ear inoculation compared with both intraperitoneal and middle ear inoculation. There is no change in threshold between the group of rats with cochleostomy and the control (Fisher's exact test, p < 0.05). Conclusion: A minimal threshold of bacteria is required to induce meningitis in healthy animals and is different for three different routes of infection (intraperitoneal, middle ear, and inner ear). Cochleostomy performed 4 weeks before the inoculation did not reduce the threshold of bacteria required for meningitis in all three infectious routes. This threshold model will also serve as a valuable tool, assisting clinicians to quantitatively analyze if the presence of a cochlear implant or other CNS prostheses alter the risk of meningitis.

[1]  R. Shepherd,et al.  Pneumococcal Meningitis: Development of a New Animal Model , 2006, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[2]  P. Roland,et al.  Bacterial Biofilm Formation on a Human Cochlear Implant , 2005, Otology and Neurotology.

[3]  Robert K. Shepherd,et al.  Cochlear implantation in rats: A new surgical approach , 2005, Hearing Research.

[4]  R. Burne,et al.  Bacterial Biofilms May Contribute to Persistent Cochlear Implant Infection , 2004, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[5]  J Thomas Roland,et al.  Meningitis in Cochlear Implant Recipients: The North American Experience , 2004, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[6]  C. Poje,et al.  Cochlear implantation and meningitis. , 2004, International journal of pediatric otorhinolaryngology.

[7]  G. Clark.  Cochlear implants in children: safety as well as speech and language. , 2003, International journal of pediatric otorhinolaryngology.

[8]  T. Balkany,et al.  Post-cochlear implant meningitis , 2003 .

[9]  R. Rosenfeld,et al.  Natural history of untreated otitis media , 2003, The Laryngoscope.

[10]  Owen Devine,et al.  Risk of bacterial meningitis in children with cochlear implants. , 2003, The New England journal of medicine.

[11]  F. Linthicum,et al.  Temporal bone fracture and latent meningitis: temporal bone histopathology study of the month. , 2003, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[12]  S. Leib,et al.  Current concepts in the pathogenesis of meningitis caused by Streptococcus pneumoniae , 2002, Current opinion in infectious diseases.

[13]  D. Briles,et al.  The Autolytic Enzyme LytA of Streptococcus pneumoniae Is Not Responsible for Releasing Pneumolysin , 2001, Journal of bacteriology.

[14]  T. Mitchell,et al.  Proinflammatory interactions of pneumolysin with human neutrophils. , 2001, The Journal of infectious diseases.

[15]  K. Kim,et al.  Pneumolysin Is the Main Inducer of Cytotoxicity to Brain Microvascular Endothelial Cells Caused by Streptococcus pneumoniae , 2001, Infection and Immunity.

[16]  M. Sande,et al.  Handbook of Animal Models of Infection: Experimental Models in Antimicrobial Chemotherapy , 1999 .

[17]  J. Bédos,et al.  Otogenic intracranial infections in adults , 1999, The Laryngoscope.

[18]  T. C. Thompson,et al.  Management of complications from 820 temporal bone fractures. , 1997, The American journal of otology.

[19]  J C Paton,et al.  The contribution of pneumolysin to the pathogenicity of Streptococcus pneumoniae. , 1996, Trends in microbiology.

[20]  M. Fylaktakis,et al.  Posttraumatic meningitis: bacteriology, hydrocephalus, and outcome. , 1994, Neurosurgery.

[21]  S. Kaplan,et al.  Hematogenous pneumococcal meningitis in the infant rat: description of a model. , 1991, The Journal of infectious diseases.

[22]  D. Brahams.  Hairline fracture and undiagnosed meningitis , 1991, The Lancet.

[23]  M. Kline.  Review of recurrent bacterial meningitis , 1989, The Pediatric infectious disease journal.

[24]  Y. Lau,et al.  Post-traumatic meningitis in children. , 1986, Injury.

[25]  G. O'Donoghue,et al.  Cochlear Implantation: Strategies to Protect the Implanted Cochlea from Middle Ear Infection , 1986, The Annals of otology, rhinology, and laryngology.

[26]  E. Moxon.  Experimental infections of animals in the study of Streptococcus pneumoniae. , 1981, Reviews of Infectious Diseases.

[27]  M. Finland.  Conference on the Pneumococcus: summary and comments. , 1981, Reviews of infectious diseases.

[28]  A. Smith,et al.  Haemophilus influenzae bacteremia and meningitis in infant primates. , 1980, The Journal of laboratory and clinical medicine.

[29]  E. Moxon,et al.  The infant rat as a model of bacterial meningitis. , 1977, The Journal of infectious diseases.

[30]  Moxon Er,et al.  Haemophilus influenzae meningitis in infant rats: role of bacteremia in pathogenesis of age-dependent inflammatory responses in cerebrospinal fluid. , 1977 .

[31]  E. Moxon,et al.  Haemophilus influenzae meningitis in infant rats after intranasal inoculation. , 1974, The Journal of infectious diseases.

[32]  H. Schuknecht,et al.  Pathology of the ear in pneumococcal meningitis , 2004, Archiv für klinische und experimentelle Ohren-, Nasen- und Kehlkopfheilkunde.

[33]  W. Scheld,et al.  Adult Rat Model of Meningitis , 1999 .

[34]  M. Frosch,et al.  Infant Rat Model of Acute Meningitis , 1999 .

[35]  J. Rubins,et al.  Invasive pneumococcal disease in the immunocompromised host. , 1997, Microbial drug resistance.

[36]  J. Paton,et al.  Molecular analysis of putative pneumococcal virulence proteins. , 1997, Microbial drug resistance.

[37]  P. Andrew,et al.  Relationship of structure to function in pneumolysin. , 1997, Microbial drug resistance.

[38]  P. Andrew,et al.  Biological properties of pneumolysin. , 1997, Microbial drug resistance.

[39]  V. V. Ivanova,et al.  A study of pathogenic factors of Streptococcus pneumoniae strains causing meningitis. , 1995, FEMS immunology and medical microbiology.

[40]  E. Moxon,et al.  Haemophilus influenzae meningitis in infant rats: role of bacteremia in pathogenesis of age-dependent inflammatory responses in cerebrospinal fluid. , 1977, The Journal of infectious diseases.