Graeme Clark Collection

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    Can we prevent cochlear implant recipients from developing pneumococcal meningitis?
    Wei, BPC ; Robins-Browne, RM ; Shepherd, RK ; Clark, GM ; O'Leary, SJ (Oxford University Press (OUP), 2008-01-01)
    The restoration of hearing to persons with severely or profoundly impaired hearing by means of a cochlear implant is one of the great achievements of bionics applied to medicine. However, pneumococcal meningitis in implant recipients has received high profile public attention as a result of the US Food and Drug Administration's public health notification and recent media attention. Worldwide, 118 of the 60,000 people who received cochlear implants over the past 20 years have acquired meningitis, causing deep concern in the international medical community. This review provides answers to pediatricians, internists, and infectious diseases doctors who have patients with cochlear implants and who have questions about the safety of the cochlear implant from both the clinical and scientific research perspectives. Both clinical and laboratory research support the notion that pneumococcal meningitis is more likely in patients who receive cochlear implantation, and that the surgical insertion technique and the cochlear implant design should be nontraumatic, and that all cochlear implant recipients should be offered vaccination against Streptococcus pneumoniae.
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    Pneumococcal meningitis post-cochlear implantation: preventative measures.
    Wei, BPC ; Shepherd, RK ; Robins-Browne, RM ; Clark, GM ; O'Leary, SJ (Wiley, 2010-11)
    OBJECTIVE: Both clinical data and laboratory studies demonstrated the risk of pneumococcal meningitis post-cochlear implantation. This review examines strategies to prevent post-implant meningitis. DATA SOURCES: Medline/PubMed database; English articles after 1980. Search terms: cochlear implants, pneumococcus meningitis, streptococcus pneumonia, immunization, prevention. REVIEW METHODS: Narrative review. All articles relating to post-implant meningitis without any restriction in study designs were assessed and information extracted. RESULTS: The presence of inner ear trauma as a result of surgical technique or cochlear implant electrode array design was associated with a higher risk of post-implant meningitis. Laboratory data demonstrated the effectiveness of pneumococcal vaccination in preventing meningitis induced via the hematogenous route of infection. Fibrous sealing around the electrode array at the cochleostomy site, and the use of antibiotic-coated electrode array reduced the risk of meningitis induced via an otogenic route. CONCLUSION: The recent scientific data support the U.S. Food and Drug Administration recommendation of pneumococcal vaccination for the prevention of meningitis in implant recipients. Nontraumatic cochlear implant design, surgical technique, and an adequate fibrous seal around the cochleostomy site further reduce the risk of meningitis.
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    Pneumococcal meningitis post-cochlear implantation: potential routes of infection and pathophysiology.
    Wei, BPC ; Shepherd, RK ; Robins-Browne, RM ; Clark, GM ; O'Leary, SJ (Wiley, 2010-11)
    OBJECTIVE: This review describes the current concept of pneumococcal meningitis in cochlear implant recipients based on recent laboratory studies. It examines possible routes of Streptococcus pneumoniae infection to the meninges in cochlear implant recipients. It also provides insights into fundamental questions concerning the pathophysiology of pneumococcal meningitis in implant recipients. DATA SOURCES: Medline/PubMed database; English articles after 1960. Search terms: cochlear implants, meningitis, pneumococcus, streptococcus pneumonia. REVIEW METHODS: Narrative review. All articles relating to post-implant meningitis without any restriction in study designs were assessed and information extracted. RESULTS: The incidence of pneumococcal meningitis in cochlear implant recipients is greater than that of an age-matched cohort in the general population. Based on the current clinical literature, it is difficult to determine whether cochlear implantation per se increases the risk of meningitis in subjects with no existing risk factors for acquiring the disease. As this question cannot be answered in humans, the study of implant-related infection must involve the use of laboratory animals in order for the research findings to be applicable to a clinical situation. The laboratory research demonstrated the routes of infection and the effects of the cochlear implant in lowering the threshold for pneumococcal meningitis. CONCLUSION: The laboratory data complement the existing clinical data on the risk of pneumococcal meningitis post-cochlear implantation.
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    Meningitis after cochlear implantation: the risk is low, and preventive measures can reduce this further
    Wei, Benjamin P. C. ; Clark, Graeme M. ; O'Leary, Stephen J. ; Shepherd, Robert K. ; Robins-Browne, Roy M. ( 2007)
    Since the 1980s, more than 80 000 people have received cochlear implants worldwide. These implants are designed to enable people who are severely or profoundly deaf to experience sound and speech. Since 1990, implantation has become standard treatment for people who cannot communicate effectively despite well fitted hearing aids. Children who are deaf when they are born can perceive sound and learn to speak if they receive cochlear implants at a young age (ideally under 18 months). The use of cochlear implants has been thought to be safe. But since 2002 the number of patients with meningitis related to cochlear implantation has increased worldwide. Mortality and neurological complications after meningitis are high. We need to investigate the reasons for this and look at measures to reduce them.
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    Threshold shift: effects of cochlear implantation on the risk of pneumococcal meningitis
    Wei, Benjamin P. C. ; Shepherd, Robert K. ; Robins-Browne, Roy M. ; Clark, Graeme M. ; O'Leary, Stephen J. ( 2007)
    Unavailable due to copyright.
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    Effects of inner ear trauma on the risk of pneumococcal meningitis
    Wei, Benjamin P. C. ; Shepherd, Robert K. ; Robins-Browne, Roy M. ; Clark, Graeme M. ; O'LEARY, STEPHEN ( 2007)
    Objective: To examine the risk of pneumococcal meningitis in healthy rats that received a severe surgical trauma to the modiolus and osseous spiral lamina or the standard insertion technique for acute cochlear implantation. Design: Interventional animal studies. Subjects: Fifty-four otologically normal adult Hooded- Wistar rats. Interventions: Fifty-four rats (18 of which received a cochleostomy alone; 18, a cochleostomy and acute cochlear implantation using standard surgical techniques; and 18, a cochleostomy followed by severe inner ear trauma) were infected 4 weeks after surgery with Streptococcus pneumoniae via 3 different routes (hematogenous, middle ear, and inner ear) to represent all potential routes of bacterial infection from the upper respiratory tract to the meninges in cochlear implant recipients with meningitis. Results: Severe trauma to the osseous spiral lamina and modiolus increased the risk of pneumococcal meningitis when the bacteria were given via the middle or inner ear (Fisher exact test, P<.05). However, the risk of meningitis did not change when the bacteria were given via the hematogenous route. Acute electrode insertion did not alter the risk of subsequent pneumococcal meningitis for any route of infection. Conclusions: Severe inner ear surgical trauma to the osseous spiral lamina and modiolus can increase the risk of pneumococcal meningitis. Therefore, every effort should be made to ensure that cochlear implant design and insertion technique cause minimal trauma to the bony structures of the inner ear to reduce the risk of pneumococcalmeningitis.
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    Assessment of the protective effect of pneumococcal vaccination in preventing meningitis after cochlear implantation
    Wei, Benjamin P. C. ; Robins-Browne, Roy M. ; Shepherd, Robert K. ; AZZOPARDI, KRISTY ; Clark, Graeme M. ; O'Leary, Stephen J. ( 2007)
    Objectives: To examine if a 23-valent pneumococcal capsular polysaccharide vaccine (PPV23) reduces the risk of meningitis in healthy rats after cochlear implantation. Design: Interventional animal study. Interventions: Thirty-six rats (18 immunized and 18 unimmunized) received cochlear implantations and were then infected with Streptococcus pneumoniae via 3 different routes (hematogenous, middle ear, and inner ear) in numbers sufficient to induce meningitis. Results: The rats with implants that received PPV23 were protected from meningitis when the bacteria were delivered via the hematogenous and middle-ear routes (Fisher exact test P<.05). However, the protective effect of the vaccine in the rats with implants was only moderate when the bacteria were inoculated directly into the inner ear. Conclusions: Our animal model clearly demonstrates that immunization can protect healthy rats with a cochlear implant from meningitis caused by a vaccine-covered serotype. This finding supports the notion that all current and future implant recipients should be vaccinated against S pneumoniae.
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    Protective effects of local administration of ciprofloxacin on the risk of pneumococccal meningitis after cochlear implantation
    Wei, Benjamin P. C. ; Robins-Browne, Roy M. ; Shepherd, Robert K. ; AZZOPARDI, KRISTY ; Clark, Graeme M. ; O'Leary, Stephen J. ( 2006)
    Objectives: To determine whether ciprofloxacin retains its antimicrobial activity after storage with Healon at ambient temperature and at 37°C over 5 weeks and then to establish whether the application of ciprofloxacin/Healon onto scala tympani electrode arrays reduces the risk of meningitis in implanted rats inoculated with S. pneumoniae. Study Design: In vitro laboratory and in vivo animal studies Methods: The antibacterial activity of three concentrations of ciprofloxacin/Healon (7.5, 75, and 750 µg/mL) was examined over 5 weeks at both ambient temperature (23°C) and body temperature (37°C). Thirty-six rats (18 implanted with ciprofloxacin [750 mg/mL]/Healon-coated electrode array and 18 without the coating) were infected with S. pneumoniae 4 weeks after implantation by way of three different routes of infection (hematogenous, middle ear, and inner ear) and observed for the development of meningitis. Results: The antibacterial activity of ciprofloxacin/Healon was maintained over 5 weeks at both 23°C and 37°C. The implanted rats with the ciprofloxacin/Healon-coated electrode array were protected from meningitis when the bacteria were given by way of the hematogenous route (Fisher’s exact test, P = .008) but not when the bacteria were inoculated directly into the middle or inner ear. However, the time to develop meningitis was significantly longer in rats implanted with a coated array, irrespective of the route of inoculation (P < .05, log rank test). Conclusion: Our animal model demonstrated that a ciprofloxacin-coated electrode array can protect healthy implanted rats from meningitis when the route of infection is hematogenous and can delay the onset of meningitis when bacteria are inoculated directly into the middle or inner ear.
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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 ( 2006)
    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 x 10[to the power of 6] and 1 x 10[to the power of 8] 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[to the power of 10] CFU i.p., 3 x 10[to the power of 8] CFU middle ear, and I x 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.
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    Pneumococcal meningitis threshold model: a potential tool to assess infectious risk of new or existing inner ear surgical interventions
    Wei, Benjamin P. C. ; Shepherd, Robert K. ; Robins-Browne, Roy M. ; Clark, Graeme M. ; O'LEARY, STEPHEN ( 2006)
    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 implantor other CNS prostheses alter the risk of meningitis.