Research at BioMed

Understanding and combating catheter-related complications

Using light-emitting bacteria to investigate why and how bacteria grow on urinary catheters

Indwelling urinary catheters are used to manage bladder drainage in patients with voiding difficulties or incontinence. They are often considered a ‘last resort’ due to the complications that can arise.  One of these is blockage, which can happen without warning.  The BioMed and the University of the West of England, Bristol, are collaborating on a project to investigate why and how particular types of bacteria grow on urinary catheters causing catheter blockage and infection in the patient.   We are using light-emitting bacteria, known as bioluminescent reporters, to detect the way the bacteria stick to catheters and move along them. Monitoring light emission makes it easier for us to follow what the (tiny) bacterial cells are up to!

Our first challenge is to develop bioluminescent forms of the type of bacteria which commonly infect urinary catheters. Once this has been achieved we will simulate bacterial growth within urinary catheters in the laboratory and try to discover whether the bacteria grow in particular locations within the catheter and what conditions encourage them to grow and cause catheter blockage. Finally, we will study whether the bioluminescent reporters can enter into bladder cells, which we can grow in the laboratory. This may give us some clues as to how they can infect the human bladder and avoid treatment with some antibiotics.

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Investigation of whether novel disinfectants (electrochemically activated solutions), are effective against the bacteria present in urinary catheter bags

Patients who rely on an indwelling catheter for draining the bladder often use a drainage bag into which the urine collects.  Common practice dictates that the bag is replaced every 5-7 days while the catheter itself may be replaced between 28 and 90 days, depending on the type of catheter.  If a patient suffers from a Proteus mirabilis infection, the catheter may be replaced more frequently due to blockage caused by a mineral biofilm. 

Although the use of a closed drainage system is now standard practice, infection can still occur via the intraluminal route.  If the drainage tube is disconnected from the catheter bacteria have a chance to enter into the internal lumen and infect.  Contamination of the tap of the drainage bag can occur during regular opening to drain urine.  Damage of a drainage bag can allow bacteria to enter the closed system as well.  If we can maintain a sterile environment within the drainage bag, we can reduce the risk of infection.

 

Figure 1

Figure 1. Red arrow denotes intraluminal route of bacteria

This study set out to determine whether a novel disinfectant was active against a range of urinary tract pathogens and could therefore be used to maintain a sterile environment within the drainage bag.  ECAS (ElectroChemically-Activated Solution) is generated from low halide salt solutions via specially designed electrolytic cells.  The use of ECAS has been exploited widely outside of Europe. ECAS has been used for cooling tower disinfection, swimming pool sanitation, dermatological washing, cleaning and dressing of wounds, and disinfection of instruments.  The main active components are thought to be hypochlorous acid, free radicals and a variety of mixed oxidants.

Sets of in vitro bladder models were infected with a high bacterial population and ~80ml of ECAS was put into the drainage bag.  Over a period of 8 hours the ECAS was able to decontaminate the urine in the bag thus reducing the risk of infection via the intraluminal route.  ECAS was very active against Pr. mirabilis, Ps. aeruginosa, K. pneumoniae, Ent. faecalis and E. coli, with weak solutions (between 1-2%) killing all bacteria in lab tests.  It was found that the efficacy of ECAS was inhibited by organic load.  This was overcome by using more of the disinfectant to counter any inhibition.  The activity of ECAS also reduces over time.  This allows for disposal of excess solution without the risk of adverse environmental consequences. 

This study has demonstrated that ECAS is an effective disinfectant at low concentrations and could have beneficial patient outcomes especially in hospital or nursing home settings, preventing cross contamination of the drainage system.   We would like to see if this approach could reduce the rate of infections in a clinical setting.

This study was funded by North Bristol NHS Trust in collaboration with the University of the West of England.

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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.

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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 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

 

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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)

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Investigation of whether the use of urinary catheters causes inflammation of the bladder

The use of a long term urinary catheter, which can be inserted either through the urethra or through the abdomen (suprapubic), can cause complications. These include urinary tract infections (UTIs); tissue damage arising from trauma, pressure and/or inflammatory reactions; recurrent catheter blockage caused by minerals deposited from the urine; and frequent bladder spasm which may result in leakage and/or the catheter being expelled.

To empty the bladder, patients can either use a catheter bag or a valve. With a catheter bag, urine is allowed to drain continuously into the bag, rather than the bladder filling and emptying naturally. When a valve is attached to the end of the catheter, the bladder can fill when the valve is closed and be emptied when the valve is opened at a convenient time and place for the user. Continual drainage creates an abnormal state for the bladder due to the loss of the natural filling and emptying cycle, and the study will investigate whether there are any differences in the degree of inflammation between patients who use catheter bags and those who use catheter valves.

The BUI are collaborating with the Continence Technology and Skin Health Group at the University of Southampton , who are leading the project. The BUI commenced the study in May 2009 and are asking patients who have a catheter to participate in a single one hour visit. Recruitment will last for up to 6 months.

 

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