Slow-Release Antibiotic Middle Ear Implant for Glue Ear Treatment

Lead Research Organisation: University of Nottingham
Department Name: School of Medicine

Abstract

Glue ear is a common cause of deafness in childhood, affecting up to 75% of children. It is caused by persistent bacterial infection (biofilm) that is impossible to cure with traditional antibiotic treatment, but can be resolved with a prolonged course of high dose antibiotics given directly to the affected area. The current treatment of severe persistent glue ear consists of grommet (ventilation tube) insertion, but although this is the commonest surgical procedure in children, it only removes the glue fluid and does not address the underlying problem of bacterial biofilm infection. Therefore, a quarter of children require further grommet insertion within 2 years of initial surgery, and management of glue ear and its long-term complications presents a significant problem and workload to the clinician.
We plan to investigate a novel alternative strategy for glue ear treatment, by developing a slow-release antibiotic implant that can be inserted into the middle ear to release antibiotics at a high dose over a prolonged period of time to eradicate infection. This project in a laboratory setting will develop the slow-release antibiotic implant and test its effectiveness against bacterial biofilm infection.

Technical Summary

BACKGROUND: Otitis media with effusion (OME, glue ear) is a common cause of hearing loss in childhood, affecting up to 75% of children, and treatment with grommets (ventilation tube) insertion is the commonest indication for surgery in children. OME is thought to be caused by bacterial infection, with bacteria persisting in the middle ear as biofilms (adherent three-dimensional structured communities of bacteria growing in a self-produced extracellular matrix). Such bacteria are recalcitrant (resistant) to conventional antibiotic treatments, accounting for the failure of oral antibiotics to confer a lasting benefit in children with OME. However, whilst grommet insertion removes glue (a product of increased mucous production by the middle ear mucosa irritated by bacterial presence), it does not address the underlying problem of bacterial infection. Therefore, a quarter of children require further grommet insertion within 2 years of initial surgery.
AIM: We plan to investigate a novel alternative strategy for glue ear treatment, by developing a slow-release antibiotic implant that can be inserted into the middle ear to release antibiotics at a high dose over a prolonged period of time to eradicate infection.
METHODS: This laboratory project will optimise the formulation for surgical handling. Antibiotic release will be assessed using serial dilution and High Performance Liquid Chromatography. Microbiological effectiveness will be assessed using minimum inhibitory concentration agar plate assay, and biofilms cultured on silicone tubing will be used to assess effectiveness of the antibiotic implant against established biofilms in a novel in vitro model
POTENTIAL APPLICATION: If successful, we would expect patients to benefit from this research within less than 5 years. The antibiotic implant may reduce recurrence of OME and associated long-term complications including hearing loss, and may replace the need for grommet insertion with a simpler procedure involving just the placement of the antibiotic implant. As the project uses existing antibiotics and slow-release techniques for a new application, better treatment of glue ear could be developed at very little cost. Following laboratory research, a clinical trial would be planned in association with the National Biomedical Unit in Hearing.

Publications

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Daniel M (2012) Bacterial involvement in otitis media with effusion. in International journal of pediatric otorhinolaryngology

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Hoskison E (2013) Drug delivery to the ear. in Therapeutic delivery

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Qureishi A (2014) Update on otitis media - prevention and treatment. in Infection and drug resistance

 
Description Research Grant / MIO
Amount £3,000 (GBP)
Organisation The Midland Institute of Otology 
Sector Academic/University
Country United Kingdom
Start 11/2010 
End 11/2015
 
Description Research Grant / Mason Medical
Amount £9,314 (GBP)
Organisation Mason Medical Research Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2011 
End 08/2011
 
Description Research Grant / Sir Samuel Scott of Yews
Amount £1,500 (GBP)
Organisation Sir Samuel Scott of Yews Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2011 
End 05/2012
 
Title Biofilm model 
Description In vitro biofilm model to study biofilms implicated in glue ear 
Type Of Material Model of mechanisms or symptoms - in vitro 
Provided To Others? No  
Impact The model allowed our group to study biofilms in vitro without need for animal studies 
 
Description Antibiotic pellets 
Organisation Nottingham University Hospitals NHS Trust
Department Nottingham University Hospitals Charity
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Carried out the actual work, led the project
Collaborator Contribution Access to facilities. Intellectual contributionAccess to facilities. Intellectual contributionIntellectual input
Impact Output from research project as a whole is the result of collaboration. The work has led to numerous national and international presentations. The project is multidisciplinary, involving departments of Otolaryngology (University and NHS), Othopaedic and Accident Surgey / Biomaterials-Related Infection Group, School of Pharmacy, and the National Biomedical Research Unit in Hearing.
Start Year 2009
 
Description Antibiotic pellets 
Organisation University of Nottingham
Department School of Biomedical Sciences Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution Carried out the actual work, led the project
Collaborator Contribution Access to facilities. Intellectual contributionAccess to facilities. Intellectual contributionIntellectual input
Impact Output from research project as a whole is the result of collaboration. The work has led to numerous national and international presentations. The project is multidisciplinary, involving departments of Otolaryngology (University and NHS), Othopaedic and Accident Surgey / Biomaterials-Related Infection Group, School of Pharmacy, and the National Biomedical Research Unit in Hearing.
Start Year 2009
 
Description Antibiotic pellets 
Organisation University of Nottingham
Department School of Molecular Medical Sciences Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution Carried out the actual work, led the project
Collaborator Contribution Access to facilities. Intellectual contributionAccess to facilities. Intellectual contributionIntellectual input
Impact Output from research project as a whole is the result of collaboration. The work has led to numerous national and international presentations. The project is multidisciplinary, involving departments of Otolaryngology (University and NHS), Othopaedic and Accident Surgey / Biomaterials-Related Infection Group, School of Pharmacy, and the National Biomedical Research Unit in Hearing.
Start Year 2009
 
Description Antibiotic pellets 
Organisation University of Nottingham
Department School of Pharmacy
Country United Kingdom 
Sector Academic/University 
PI Contribution Carried out the actual work, led the project
Collaborator Contribution Access to facilities. Intellectual contributionAccess to facilities. Intellectual contributionIntellectual input
Impact Output from research project as a whole is the result of collaboration. The work has led to numerous national and international presentations. The project is multidisciplinary, involving departments of Otolaryngology (University and NHS), Othopaedic and Accident Surgey / Biomaterials-Related Infection Group, School of Pharmacy, and the National Biomedical Research Unit in Hearing.
Start Year 2009
 
Description Pellet toxicity 
Organisation University of Leicester
Department College of Medicine, Biological Sciences and Psychology
Country United Kingdom 
Sector Academic/University 
PI Contribution Biofilm and drug delivery expertise
Collaborator Contribution Middle and inner ear toxicity expertise
Impact none to date
Start Year 2012
 
Title Antibiotic pellet 
Description Antibiotic pellet tested in vitro against biofilms (with ultimate clinical aim of treating glue ear). The product as it stands needs refinement and is not suitable for clinical trials at this stage. Principally funded by MRC 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2011
Development Status On hold
Impact At present stage the product needs further refinement. 
 
Description News 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Primary Audience Media (as a channel to the public)
Results and Impact Report on local news, press release

Publicity to local public, press release on line
Year(s) Of Engagement Activity 2011