Otitis Media with Effusion (OME) is a common childhood condition leading to hearing loss, and its treatment with ventilation tubes (VTs) is one of the commonest surgical procedures. However, aetiology of OME is poorly understood, and its current treatment requires improvement as OME frequently recurs once VTs extrude. The first, clinical part of this thesis showed that 63.6% of children randomised to VT insertion in a clinical trial will require VTs again, and even with additional adenoidectomy the need for repeat surgery remains high. Although published national guidelines set out criteria for surgery, the multicentre study presented here showed that only 32.2% of children that had VTs met these criteria, and guidelines' publication had limited impact on clinical practice. The second, laboratory part of this thesis demonstrated the importance that bacteria and biofilms play in aetiology of OME, as live bacteria were demonstrated in 91.9% of middle ear effusions (using culture and confocal microscopy). Following from this, a Staphylococcus aureus biofilm model was developed, and used to show that biofilm eradication requires antibiotic (rifampicin and lindamycin) levels 1,000 times higher than those required to inhibit planktonic bacteria, over a period of 2-3 weeks. To achieve this in the middle ear, a local delivery strategy using biodegradable poly (Iactic-coglycolic acid) antibiotic pellets was proposed. Drug release from these pellets was investigated with High Performance Liquid Chromatography and Serial Plate Transfer Testing, which demonstrated that antibiotics can be released for up to 3 weeks. Importantly, the pellets were able to eradicate biofilms in the in vitro model. This thesis has shown that current OME treatment has significant deficiencies, but better understanding of OME pathogenesis raises the possibility of rational new therapeutic strategies. Biodegradable antibiotic pellets designed to eradicate OME biofilms may be a better future treatment that could improve the lives of countless children.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:594418 |
| Date | January 2013 |
| Creators | Daniel, Matija |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/28069/ |
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