Fisher, Leanne
(2011)
Development and evaluation of an antimicrobial urinary catheter.
PhD thesis, University of Nottingham.
Abstract
Over the past few years the healthcare setting has seen a vast increase in the use of medical devices and whilst this may have improved clinical outcomes for patients their increase in use has given rise to an increase in medical - device associated infections. It has been reported that urinary tract infections (UTIs) account for up to 40% of all healthcare associated infections and about 80% of those are associated with catheter use [1]. Urinary catheters are hollow, flexible, tubular devices designed to drain urine when inserted into a patient‟s bladder. They are widely used both on patients requiring short - term urinary catheterisation e.g. during and after some types of surgical procedures or long - term urinary catheterisation e.g. due to urinary incontinence. For patients undergoing long - term indwelling urinary catheterisation (LTC) it is almost inevitable that their catheter will become colonised with bacteria and a biofilm (an accumulation of microorganisms and their extracellular products that form a functional, structured community on a surface) [2] develop which can result in a symptomatic or asymptomatic catheter associated urinary tract infection (CAUTI). Infections associated with biofilms are difficult to treat due to the bacteria within the biofilm being insusceptible to antibiotic treatment. Often to resolve the infection, removal and replacement of the catheter is required and antibiotic treatment if necessary. Certain patients may require their catheter to be changed frequently, often causing considerable distress and morbidity and giving rise to increased medical costs. Biomaterials used to produce long - term urinary catheters that are able to completely resist bacterial colonisation for significant periods, remain elusive. The development of antimicrobial urinary catheters has, however, shown some success in clinical trials but only in the short-term.
This project proposes to modify a silicone urinary catheter used for LTC by impregnating it with a suitable combination and concentration of antimicrobial agents. The aim of the study is to develop an antimicrobial catheter that will provide protection from bacterial colonisation and subsequent biofilm development by the principle organisms involved in CAUTIs over a prolonged period (12 weeks).
Silicone material was processed using an impregnation method. A variety of agents were assessed using drug screening tests to establish their potential duration of antimicrobial activity and ability to prevent bacterial colonisation. The combination of agents showing the most potential were selected and impregnated into the catheter material. They were: rifampicin, sparfloxacin and triclosan. Further testing involved the development of an in - vitro model designed to test the ability of the antimicrobial catheter to resist colonisation following repeated bacterial challenges. The emergence of bacterial resistance was also monitored during this time. In addition, the total antimicrobial content, drug release profiles and uniformity of drug distribution were elucidated using high performance liquid chromatography (HPLC) and time of flight secondary ion mass spectroscopy (ToF-SIMS) respectively. The effect impregnating antimicrobial agents into the catheter had on its surface properties and the impact on mechanical performance of the catheter shaft and balloons were also examined.
Drug screening tests revealed a combination of rifampicin, sparfloxacin and triclosan had the potential to deliver a long duration of protective activity against principal uropathogens. In - vitro model results demonstrated the antimicrobial catheter was able to prevent colonisation by Escherichia coli and Meticillin Resistant Staphylococcus aureus for >12 weeks, Klebsiella pneumoniae and Proteus mirabilis for 8 weeks but only 8 days against Enterococcus faecalis. K.pneumoniae and P.mirabilis colonised catheters did, however, show an increase in the sparfloxacin and triclosan minimum inhibitory concentrations (MICs), highlighting that the development of bacterial resistance could be an issue. The catheter was found to contain (w/w) 0.006% rifampicin, 0.16% sparfloxacin and 0.17% triclosan of which 19.8% sparfloxacin and 29.9% triclosan were released by a diffusion process over the first 28 days. Rifampicin release was not detected possibly due to low concentrations. With the drug release trend suggesting a continued steady release of sparfloxacin and triclosan above the MIC and with 80.2% of sparfloxacin and 70.1% of triclosan remaining, this would suggest there should be sufficient drug to provide protection from bacterial colonisation over a 12 week duration. However, why the MICs increased as catheters became colonised with K.pneumoniae and P.mirabilis could be due to a number of factors.
ToF-SIMS revealed the drugs which could be traced (sparfloxacin and triclosan) were mostly uniformly distributed on the catheter surface, with some drug localization being seen which may have added to the initial burst effect and could be important in the prevention of bacterial colonisation during catheter insertion. Surface analysis techniques also showed the incorporation of antimicrobial agents lead to an increase in the surface hydrophilicity but following exposure to an aqueous environment no difference was seen compared to control catheters. As drugs eluted from the catheter the surface topography marginally deteriorated but the impact of this in terms of bacterial colonisation is not thought to be of a clinical significance. No adverse affect to the mechanical performance of the antimicrobial catheter shaft or balloon compared to the conventional silicone Foley urinary catheter was shown, indicating that it would be as mechanically stable as the catheter in clinical use and therefore suitable if applied to clinical practice.
Further work on the drug release concentrations and ratios are needed to help overcome the potential of bacterial resistance. The catheter could have a greater effect on reducing bacterial colonisation and potential for resistance development if drug concentrations were adjusted to release at higher concentrations and equal ratios and more data could be gathered if drug release studies were taken to the end point of 12 weeks rather than 28 days. In - vitro model challenges using urine as the perfusion medium and a larger array of microorganisms is required and investigations are also necessary to assess the antimicrobial catheters ability to prevent encrustation, a further complication of LTC.
This preliminary study has shown with further work there is potential that the antimicrobial catheter could have a substantial effect on reducing/delaying colonisation by several of the main organisms involved in CAUTIs over a prolonged course. This in turn would help reduce CAUTI rates, reduce the frequency at which catheters need to be replaced and improve the quality of life for patients on LTC.
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