Sensor and Modulation as a Strategy for Catheter Management

A major complication experienced by up to 50% of patients undergoing long-term catheterization is encrustation and blockage. Problems arise chiefly as a consequence of infection of the catheterised urinary tract by bacteria that produce the enzyme urease, particularly Proteus mirabilis. This enzyme is able to convert the urea in urine to ammonia which results in a rapid rise in the urinary pH and precipitation of calcium and magnesium crystals which are deposited around the eye hole of the catheter and along the luminal surface. The crystalline material is hard and abrasive and can rapidly block the flow of urine through the catheter. Typically the issue is dealt with by “crisis management”. The community nurse or general practitioner will be called at any time of the day or night to attend to patients in acute discomfort with urinary retention or incontinence from urine bypassing the catheter. Work carried out with the BioMed Centre has investigated the cause and ways of combating this problem.

Catheter Encrustation | Early Warning Sensor | Citrate |
Effect of Valves | Construction of Bioluminescence

Causes of catheter encrustation; the effects of pH

This prospective study looked at a group of long-term catheter users infected with Proteus bacteria, the most common causer of catheter encrustation. It investigated how much the rate of catheter blockage varies between patients, what the reasons for this might be, and if it might be possible to have Proteus infection but not catheter blockage. Proteus organisms colonise the catheter surfaces, forming biofilm communities embedded in an adhesive polysaccharide matrix. The enzyme urease produced by the bacteria hydrolyses urea, an end-product present in urine, to form ammonia which raises the pH of the urine. Normally the voiding pH of urine (pH v) is below its nucleation pH (pH n), the pH at which calcium and magnesium salts precipitate out of solution. A clear margin between the two values is usually present. However when Proteus mirabilis infects the urinary tract, its urease activity can elevate the voiding pH above the nucleation pH so that crystals of magnesium ammonium phosphate (struvite) and calcium phosphate (hydroxyapatite)form inside the catheter and become trapped in the biofilm. The continued development of these encrustations eventually blocks the catheter lumen. All types of catheter currently available are vulnerable to blockage by crystalline P. mirabilis biofilms.

It is known that catheter blockers tend to have a higher pH than non-blockers. We found that people whose catheters took longer to block tended to have a higher nucleation pH than the rapid blockers, but there was no difference in voided urine pH. It appears that nucleation pH is not fixed for an individual and so could possibly be manipulated with treatment to slow down the encrustation process.

S Mathur et al. Prospective study of individuals with long-term urinary catheters colonized with Proteus species. BJU Int 2006; 97: 121-8

An early warning catheter encrustation sensor

Catheter blockage is unpredictable. A pH sensor to detect the rise in urinary pH following infection with P. mirabilis has been developed by Dr David Stickler and Professor Mark Waters . The sensors are strips of polymer placed in the urinary drainage bag and which change from yellow to dark blue when the crystalline biofilm begins to form on catheter surfaces. In laboratory bladder models, the sensors signalled positive on average 42 hours prior to blockage. Electron microscopy also confirmed that at this point, encrustation had started to form. A clinical study on a group of 20 catheterised patients has also shown promising results. This sort of early warning of encrustation gives patients and healthcare professionals time to take action to avoid the crisis of catheter blockage.

Stickler DJ et al. A sensor to detect the early stages in the development of crystalline Proteus mirabilis biofilm on indwelling bladder catheters. J Clin microbial 2006 Apr; 44(4):1540-2

The pH sensor is currently undergoing some modifications and further laboratory and clinical studies are to be undertaken.

Modulation of catheter encrustation by increasing fluid intake with citrate-containing drinks

The pH at which calcium and magnesium crystals precipitate from urine is known as the nucleation pH (pH n). Normally the voided urinary pH (pH v)is below its pH n. When P. mirabilis infects the urinary tract however, its urease activity can elevate the pH v above the pH n, crystals form and the catheter encrusts. Many long-term catheterised patients drink very little and consequently their urine samples have a very low pH n values. Research work has shown that it is possible to manipulate pH n of urine simply by increasing fluid intake and supplementing the diet with citrate containing drinks such as orange or lemon juice. In this way the pH n can be raised above the urinary pH which normally results from P. mirabilis infection. A small clinical study has demonstrated that citrated drinks are effective at raising the pH n within patients undergoing long term catheterisation and funding is being sought to do a larger clinical study.

Suller MT, Anthony VJ, Mathur S, Feneley RC, Greenman J, Stickler DJ. Factors modulating the pH at which calcium and magnesium phosphates precipitate from human urine. Urol Res 2005 Aug;33(4):254-60

Stickler DJ, Morgan SD. Modulation of crystalline Proteus mirabilis biofilm development on urinary catheters. J Med Microbiol 2006 May; 55 (Pt 5): 489-94

The effect of valves on catheter encrustation

It has been suggested that catheter valves improve the care of long-term catheterised patients. This study examined the effect they may have on catheter encrustation. Laboratory models of the catheterised bladder were infected with Proteus and urine either allowed to drain continuously or regulated by valves to drain intermittently. The time taken for catheters to block under the different regimes was recorded. When a manual valve was used to drain urine the time to blockage of catheters was significantly longer than catheters on continuous drainage. Electron microscopy confirmed that encrustation was less extensive on the valve regulated catheters. Valves may also help to maintain bladder tone and capacity and prevent the need to have a urine drainage bag

Sabbuba NA et al. Does the valve regulated release of urine from the bladder decrease encrustation and blockage of indwelling catheters by crystalline Proteusmirabilis biofilms? The Journal of Urology 2005; 173 (262-266)

Construction of Bioluminescent Pr. mirabilis strains to investigate the pathogenesis of urinary catheters.

Debbie Lewis a post – doctoral research fellow is working in collaboration with UWE (University of the West of England) and the BioMed Centre using bioluminescence as a molecular tool for the study of catheter encrustation and blockage. Using molecular techniques a bioluminescent gene has been inserted into Pr. mirabilis which enables the growth of the organism to be monitored by the detection of light emitted from the growing organism. This technique wil enable colonisation by Pr. mirabilis to be followed in real time, non-destructively, allowing in situ determination of the circumstances under which this microorganism initiates biofilm formation within the catheter lumen.