Studies on slow release antibiotic middle ear pellets

Hoskison, Emma (2019) Studies on slow release antibiotic middle ear pellets. PhD thesis, University of Nottingham.

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Otitis Media with Effusion (OME) is the commonest cause of paediatric hearing impairment globally. Antibiotic laden pellets placed in the middle ear (ME) present a potential novel treatment strategy for OME disrupting the middle ear biofilm and avoiding systemic side effects. In vitro studies of Staphylococcus Aureus biofilm eradication with pellets laden with rifampicin and clindamycin demonstrate a future potential OME treatment and this study aims to establish the safety of these pellets in vivo.

Rifampicin (1.8mM) and clindamycin (35.3mM) loaded pellets made of poly lactic-co-glycolic acid and pluronic were surgically placed in guinea pig middle ears.

Auditory Brainstem Responses (ABRs) thresholds between 8-30 kHz were tested over 16 weeks alongside controls to assess for ototoxicity; amplitudes and latencies studied to assess for neurotoxicity. At one week post insertion of antibiotic laden pellets, marked ABR threshold elevation (15-40 dB) was observed and persisted (25-40 dB) at week 16 without accompanying changes in ABR wave amplitudes and latencies. This pattern therefore does not support a neurotoxic mechanism.

Representative cytocochleograms and immunofluorescence of the cochleas did not exhibit any appreciable frank outer or inner hair cell loss from the guinea pigs loaded with rifampicin and clindamycin pellets. This suggests that the pellets are not causing threshold elevation via an ototoxic mechanism.

ME histology revealed pellet remnants causing a moderate inflammatory response persisting at 16 weeks. With evidence of chronic inflammation in the middle ear, an associated ME effusion which has been undetected experimentally may underlie the ABR threshold elevation seen with rifampicin and clindamycin laden pellets. Confined to the middle ear, this may also explain the lack of IHC and OHC damage.

As a delivery vehicle to the ME, PLGA and Pluronic pellets have potential, but further studies are required on their antibiotic carriage to the middle ear before in vivo use.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Baguley, David
Hartley, Doug
Keywords: Antibiotic loaded pellets
Subjects: W Medicine and related subjects (NLM Classification) > WV Otolaryngology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 56413
Depositing User: Hoskison, Emma
Date Deposited: 23 Aug 2019 13:28
Last Modified: 07 May 2020 10:15

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