Biomaterial modulation for diagnostic and therapeutic benefit in catheter-associated urinary tract infection

Duggan, Katrina 2021. Biomaterial modulation for diagnostic and therapeutic benefit in catheter-associated urinary tract infection. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Catheter-associated urinary tract infections (CAUTIs) are associated with urinary catheters biofilms. The overarching aim of this research was to identify biocidal agents that when incorporated into silicone elastomers inhibited such biofilm formation. In solution and when incorporated into the silicone matrix, triclosan and triclosan acetate exhibited broad-spectrum activity against planktonic cultures. Both agents inhibited S. aureus, K. pneumoniae, P. stuartii and P. mirabilis, whilst triclosan also had inhibited Escherichia coli and Candida albicans. Serratia marcescens and Pseudomonas aeruginosa were resistant. Mechanical properties of silicone were not negatively affected by incorporation of these antimicrobials, and elongation strength was increased. This would be advantageous for a urinary catheter as significant forces may be applied during device removal or by an attached drainage bag. Additionally, triclosan and triclosan acetate were released from bulk-loaded silicone over 12 weeks, with the latter providing the highest sustained release rate. A 3D printable silicone elastomer containing 1% triclosan was developed with superior mechanical properties, compared to compression moulded silicone, and inhibited growth of P. mirabilis, E. coli and S. aureus. Dip-coating Foley catheters in a silicone formulation containing 0.2% triclosan or triclosan acetate prevented catheter blockage by P. mirabilis in an in-vitro bladder model of CAUTI. A 1% coating of the novel imidazolium compound 3-hexadecyl-1-isopropyl-1Himidazole-3-ium bromide ([HL2 ] Br) in silicone reduced growth of S. aureus and C. albicans. A panel of signalling molecules were evaluated to determine their activity and sensitivity against numerous CAUTI causing pathogens with the most promising compounds, namely bromothymol blue (BTB) and resazurin selected for incorporation into biomaterials. The aim was to develop biomaterial sensors to signal early CAUTI and thus, facilitate improved management. A silicone sensor incorporating (BTB) changed colour from yellow to dark blue in the presence of ammonium ions generated by urease positive bacteria. Increasing the surface area of this sensor reduced the signalling time of P. mirabilis infection in an in vitro bladder model by 3 h, compared with the original BTB sensor. To create a universal microbial sensor material, a range of chemicals were evaluated, and resazurin, commonly used to determine cell viability, provided the best signalling response to infection. Incorporation this agent into a biomaterial was unsuccessful, but its addition to the drainage bag in the in vitro bladder model signalled P. mirabilis infection with similar sensitivity to the BTB sensor. It is anticipated that resazurin could be used to detect multiple microbes and thus be a valuable diagnostic agent in CAUTI.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Dentistry
Subjects:	R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords:	microbial biofilms urinary tract infections catheter biomaterial
Funders:	KESS 2 - Knowledge Economy Skills Scholarships
Date of First Compliant Deposit:	12 January 2022
Last Modified:	18 Jan 2022 12:12
URI:	https://orca.cardiff.ac.uk/id/eprint/146520

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