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Title: Crystalline bacterial biofilm formation on urinary catheters by urease producing urinary tract pathogens
Author: Broomfield, Robert James
ISNI:       0000 0004 2750 2318
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2007
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The aim of this study was to compare the abilities of various urease-positive species to encrust and block catheters with crystalline biofllm. Experiments were performed in laboratory models of the catheterised bladder infected with a range of urease- producing species. The results of these experiments allowed the classification of the bacteria into three groups: rapid encrusters, slow encrusters and non-encrusters. Rapid encrusters (Pr. mirabilis, Proteus vulgaris and Providencia rettgeri) were able to raise the urinary pH to 8 - 9 and cause catheter blockage within 37 h. Slow encrusters (Morganella morganii, Staphylococcus aureus and Staphylococcus saprophytics) were able to raise the urinary pH moderately (from 6.1 to 6.89 - 7.39 over 96 h) and cause the formation of some encrustation on the catheters. Non- encrusters {Providencia stuartii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Enterobacter cloacae, Citrobacter freundii and Citrobacter koseri) were not able to raise the mean urinary pH above mean levels of 6.45 and did not form crystalline biofilm. Pr. mirabilis, Pr. vulgaris and Pv. rettgeri were also capable of rapidly encrusting silver-hydrogel coated latex catheters (Bard I.C. catheter) and nitrofurazone impregnated silicone catheters (Rochester NF catheter). There were no significant differences between the times these organisms took to block these catheters compared to all-silicone control catheters. The antimicrobial catheters also had no effect on the urinary pH generated by these organisms. The insensitivity of the three encrusting species to nitrofurazone (MICs 32- 128 ug/ml) is clearly a major factor in the failure of these catheters to prevent encrustation. The results of experiments in which the balloons of all-silicone catheters were inflated with solutions of triclosan (3 mg/ml in 0.1 M sodium carbonate) confirmed previous observations that catheter encrustation by Pr. mirabilis was prevented by this strategy. It also proved effective against Pr. vulgaris. In both cases, in contrast to the controls, the numbers of viable cells recovered from the residual urine fell steeply within 24 h, the pH of the urine dropped below its nucleation pH (pH 6.5) and the catheters drained freely for the seven day experimental period. The effect of triclosan on encrustation by Pv. rettgeri was minimal however, with no significant difference between blockage times or urinary pHs in the test and control models. While the Proteus sp. had MICs of triclosan of < 0.2 ug/ml, the value for Pv. rettgeri was 64 ug/ml. Inflating catheter balloons with a solution which generated nitric oxide proved ineffective as a means of controlling catheter encrustation. Previous studies have shown that a simple cellulose acetate / bromothymol blue sensor is capable of signalling infection by Pr. mirabilis and the early stages of catheter encrustation. Placed in the drainage bag it can give early warnings to patients, carers and nurses that catheters need to be replaced. While the use of the sensor in this way could avoid the clinical crises induced by catheter blockage, it would be of more value if an effective strategy to inhibit encrustation could be deployed when the problem is signalled. In the present study it was demonstrated that strips of the sensor polymer placed in the drainage bags changed from yellow to blue signalling the rise in urinary pH induced by infection with Pr. mirabilis, Pr. vulgaris or Pv. rettgeri . Electron microscopy confirmed that encrustation had started on the catheters at the times the sensors turned blue. Triclosan (3 mg/ml) introduced into the catheter balloons when the signal was observed was found to halt the development of the Proteus crystalline biofilms. It was concluded that an integrated sensor / modulator strategy was feasible for the control of encrustation by these species. (Abstract shortened by UMI.).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available