A clinical assessment of the performance of a sensor to detect crystalline biofilm formation on indwelling bladder catheters

OBJECTIVES: To test the ability of a sensor developed to signal infection by the organisms that generate the crystalline biofilms that encrust catheters, to give an early warning that encrustation was occurring on patients' catheters, as the care of many patients undergoing long-term bladder catheterization is complicated by the encrustation and blockage of their catheters. PATIENTS AND METHODS: Twenty patients were followed prospectively for the lifetime of one of their catheters. Sensors based on cellulose acetate/bromothymol blue were placed in the urine-collection bags, which were changed as usual at weekly intervals. The bacteriology was assessed and pH determined weekly on urine samples. Photographic records were made of the sensors twice weekly. On removal, each catheter was examined for encrustation and blockage. RESULTS: Proteus mirabilis was not isolated from five patients and in these cases the sensor colour remained golden-yellow to brown. The catheters drained for the scheduled period and showed no signs of encrustation. By contrast, the sensors turned dark blue/black in the urine of all 15 patients infected with P. mirabilis. All these patients' catheters were encrusted and in 12 the catheters blocked. The mean interval between the sensor signalling and the catheter blocking was 12 days. CONCLUSION: The cellulose acetate/bromothymol blue sensors placed in the urine collection bags are capable of signalling infection by P. mirabilis. They also signal the early stages of catheter encrustation and allow catheter replacement in ample time to avoid the clinical crises and emergency referrals caused by catheter blockage.     

Does the valve regulated release of urine from the bladder decrease encrustation and blockage of indwelling catheters by crystalline proteus mirabilis biofilms?

PURPOSE: We tested whether valve regulated, intermittent flow of urine from catheterized bladders decreases catheter encrustation. MATERIALS AND METHODS: Laboratory models of the catheterized bladder were infected with Proteus mirabilis. Urine was allowed to drain continuously through the catheters or regulated by valves to drain intermittently at predetermined intervals. The time that catheters required to become blocked was recorded and encrustation was visualized by scanning electron microscopy. RESULTS: When a manual valve was used to drain urine from the bladder at 2-hour intervals 4 times during the day, catheters required significantly longer to become blocked than those on continuous drainage (mean 62.6 vs 35.9 hours, p = 0.039). A similar 1.7-fold increase occurred when urine was drained at 4-hour intervals 3 times daily. Experiments with an automatic valve in which urine was released at 2 or 4-hour intervals through the day and night also showed a significant increase in mean time to blockage compared with continuous drainage (p = 0.001). Scanning electron microscopy confirmed that crystalline biofilm was less extensive on valve regulated catheters. CONCLUSIONS: Valve regulated, intermittent flow of urine through catheters increases the time that catheters require to become blocked with crystalline biofilm. The most beneficial effect was recorded when urine was released from the bladder at 4-hour intervals throughout the day and night by an automatic valve.     

A strategy for the control of catheter blockage by crystalline Proteus mirabilis biofilm using the antibacterial agent triclosan

OBJECTIVES: Catheter blockage by crystalline Proteus mirabilis biofilm is a common complication in patients undergoing long-term indwelling bladder catheterisation. Previously we have shown that inflating the retention balloons of all-silicone catheters with triclosan solutions prevents the encrustation process. The aim of the present work was to examine whether this strategy is effective in latex-based catheters. METHODS: Laboratory bladder models were fitted with catheters and the retention balloons inflated with water or various concentrations of triclosan. The urine was inoculated with Pr. mirabilis and the times catheters took to block recorded. RESULTS: Control catheters blocked in mean times ranging from 18 to 27 h. The pH of the urine rose from 6.1 to >8.6. In models with latex-based catheters inflated with 1-10 mg/ml triclosan, the urinary pH was controlled, the numbers of organisms in the urine was reduced and the catheters drained freely for the 7 day experimental period. Electron microscopy confirmed that crystalline biofilm was blocking control catheters. Little sign of encrustation was visible on the test catheters. CONCLUSION: Inflating the retention balloons with triclosan could have practical applications in controlling encrustation on both latex and silicone-based catheters.     

Genotyping demonstrates that the strains of Proteus mirabilis from bladder stones and catheter encrustations of patients undergoing long-term bladder catheterization are identical

PURPOSE: We established the incidence of bladder stones in patients who experienced recurrent encrustation and blockage of indwelling bladder catheters and examined the relationship between isolates of Proteus mirabilis from the stones and from the crystalline biofilms on the catheters. MATERIALS AND METHODS: The first 100 patients attending a clinic for patients experiencing problems with the management of long-term bladder catheters were studied. Flexible cystoscopy was used to detect bladder stones. Catheter encrustation was assessed visually and by electron microscopy. Bacteriological analysis was performed on the stones and catheter biofilms. P. mirabilis isolates were genotyped by pulsed field gel electrophoresis of restriction enzyme digests of bacterial DNA. RESULTS: Most patients (85%) had been referred because of catheter blockage and in 61 (72%) the catheters were encrusted. P. mirabilis was recovered from 37 of 47 encrusted catheters (79%) that were examined but not from any nonencrusted catheters. Of the 61 patients with encrusted catheters 38 (62%) had bladder stones. Pairs of isolates of P. mirabilis from the stones and the catheter biofilms from 6 patients were genotyped. The DNA profiles of each pair of isolates were identical. CONCLUSIONS: The majority of patients (62%) with recurrent catheter encrustation had bladder stones. The stones harbored the strains of P. mirabilis that rapidly colonize replacement catheters with crystalline biofilm. Flexible cystoscopy to detect and remove stones might help resolve the problem of recurrent catheter encrustation.     

Does drinking cranberry juice produce urine inhibitory to the development of crystalline, catheter-blocking Proteus mirabilis biofilms?

OBJECTIVE: To test the recommendation that to avoid the complications of long-term indwelling bladder catheterization (e.g. encrustation and blockage by crystalline Proteus mirabilis biofilms) patients should drink cranberry juice. MATERIALS AND METHODS: Urine was collected from groups of volunteers who had drunk up to 2 x 500 mL of cranberry juice or water within an 8-h period. Laboratory models of the catheterized bladder were supplied with urine from these groups and inoculated with P. mirabilis. After incubation for 24 or 48 h, the extent of catheter encrustation was determined by chemical analysis for calcium and magnesium. Encrustation was also visualized by scanning electron microscopy. RESULTS: The amounts of calcium and magnesium recovered from catheters incubated in urine pooled from individuals who had drunk 500 mL of cranberry juice was not significantly different from that on catheters incubated in pooled urine from control subjects who had drunk 500 mL of water. However, there was significantly less encrustation (P = 0.007) on catheters from models receiving urine from volunteers who had drunk 2 x 500 mL of water than on catheters incubated in models supplied with urine from volunteers who had drunk 2 x 500 mL of cranberry juice. The amounts of encrustation on these two groups of catheters were also significantly less than that on catheters incubated in models supplied with urine from volunteers who had not supplemented their normal fluid intake. (P < 0.001). Experiments in the models using artificial urine showed that increasing the low fluid intake (720 mL/24 h) characteristic of many patients undergoing long-term catheterization by factors of three and six, significantly (P < 0.01) reduced the amounts of calcium and magnesium that formed on catheters. At a simulated fluid intake of 720 mL/24 h, catheters blocked with encrustation after a mean of 42.5 h, while those supplied with urine produced from an intake of 4320 mL/24 h, drained freely for > 10 days. CONCLUSION: In this in vitro study, drinking cranberry juice did not produce urine that was inhibitory to the development of crystalline catheter-blocking P. mirabilis biofilms. The important factor in preventing catheter encrustation is a high fluid intake.     

Prospective study of individuals with long-term urinary catheters colonized with Proteus species

OBJECTIVES: To characterize the variability in the times catheters take to block with encrustation in patients who have Proteus in their urinary flora, and to identify factors responsible for modulating the rate of catheter encrustation and blockage. PATIENTS AND METHODS: Twenty patients were followed prospectively for > or = 12 weeks, with a bacteriological analysis on weekly urine samples. The pH of the voided urine samples and the pH at which crystals formed in them (the nucleation pH) were determined. Catheters were collected and examined for bacterial biofilm and crystal deposition. RESULTS: The time that catheters took to block was 2-98 days. The mean pH of the urine voided by patients designated as slow encrusters (6.9) was not significantly different (P = 0.237) from that of rapid encrusters (7.2). However, patients whose catheters took longer to block had a significantly higher mean nucleation pH (8.1 vs 7.3, P = 0.002) and significantly higher mean safety margin between their nucleation pH and voided pH (1.17 pH units vs 0.13, P = 0.003). CONCLUSION: The variation in the rate of catheter encrustation between individuals infected with Proteus is a function of the difference between the voided pH and the nucleation pH of their urine. The value of nucleation pH of an individual's urine varies widely, suggesting it should be possible to devise strategies to increase this value and thus reduce the rate of encrustation in those with urinary tract colonization by urease-positive bacteria.     

The effect of urease inhibitors on the encrustation of urethral catheters

Encrustation and blockage of indwelling urethral catheters is primarily brought about by infection of the urinary tract by Proteus mirabilis or other urease-producing species. The bacteria colonise the catheter forming a biofilm community within a polysaccharide matrix. The activity of the urease drives up the urinary pH and causes the crystallisation of calcium and magnesium phosphates in the biofilm. We have used a simple physical model of the catheterised bladder to investigate the ability of urease inhibitors to control encrustation. It was observed that acetohydroxamic acid (1.0 mg/ml) and fluorofamide (1.0 μg/ml) restricted the increase in pH of P. mirabilis-infected urine from 9.1 to 7.6. Significant reductions in the deposition of calcium and magnesium salts were also recorded on the silicone catheters. Electron microscopy confirmed that encrustation and occlusion of the catheter lumen was minimal in the presence of the urease inhibitors. The data from this in vitro study suggests that urease inhibitors, particularly fluorofamide, could have clinical applications in the prevention of catheter encrustation and blockage. Received: 22 September 1997 / Accepted: 2 January 1998     

Some observations on the diffusion of antimicrobial agents through the retention balloons of foley catheters

PURPOSE: We examined the ability of antimicrobial agents to diffuse through the retention balloons of urinary catheters and inhibit their encrustation by Proteus mirabilis. MATERIALS AND METHODS: An agar diffusion screening test was developed to detect agents capable of diffusing through catheter balloons and inhibiting the growth of P. mirabilis. The effect of inflating the balloons with antibacterials on the ability of P. mirabilis to encrust catheters was tested in laboratory models of the catheterized bladder. RESULTS: Of 18 antimicrobial agents active on P. mirabilis only mandelic acid, phenoxyethanol, nalidixic acid and triclosan diffused through all-silicone catheter balloons to produce zones of inhibition against P. mirabilis. Polyurethane balloons were permeable to gentamicin and fluoroquinolones. Experiments with silicone catheters showed that inflating balloons with mandelic acid (100 gm/l) or ciprofloxacin (10 gm/l) failed to extended the time at which catheters became blocked in models inoculated with P. mirabilis. However, nalidixic acid (50 gm/l) significantly extended the lifespan of catheters (p <0.05). Triclosan (10 gm/l) prevented the increase in urinary pH that induces crystal formation and inhibited the formation of crystalline biofilm, enabling the catheters to drain freely for the full 7-day experimental period. CONCLUSIONS: Inflation of silicone catheter retention balloons with solutions of nalidixic acid or triclosan rather than water should be considered as strategies to control catheter encrustation. Polyurethane balloons are more permeable than silicone balloons to gentamicin and the fluoroquinolones, and they should be investigated as an alternative to silicone or latex in catheter manufacture.     

The effect of EDTA instillations on the rate of development of encrustation and biofilms in Foley catheters

The aim of this research was to examine whether a daily instillation of tetra sodium ethylenediaminetetraacetic acid (EDTA) solution could reduce the rate at which encrustation by crystalline Proteus mirabilis biofilms blocks urinary catheters. Sets of three bladder models were fitted with size 14 all-silicone catheters. Tetra sodium EDTA solution was instilled into the catheter following biofilm development. Catheters were examined by digital photography and scanning electron microscopy for evidence of encrustation. The results showed that the mean time to blockage of the control catheters was 45 h for saline, 57 h for water and 67 h for those exposed to daily instillations of the EDTA solution. Statistical analysis confirmed that the mean encrustation rate on the EDTA-treated catheters was significantly lower than on the control-treated devices (P = 0.047). This in vitro study indicates that EDTA may have beneficial effects in reducing the complication of catheter encrustation and blockage by crystalline biofilms.     

A study of the structure of the crystalline bacterial biofilms that can encrust and block silver Foley catheters

The aim of this study was to examine the structure of the crystalline bacterial biofilms that encrust and block silver/hydrogel-coated latex catheters. Scanning electron microscopy was used to examine the crystalline deposits that were found encrusting catheters obtained from six patients undergoing long-term catheterization in a community setting. Large populations of bacilli and cocci were seen on all catheters developing on a basal foundation layer of crystalline material. These observations show that in patients prone to catheter encrustation, crystalline material formed in the urine can cover the surfaces of silver catheters. Extensive bacterial biofilms then develop on the crystals, shielded from the underlying silver. It is suggested that if antimicrobials are to be incorporated into catheters to prevent encrustation, they must diffuse out from the catheter surface and reduce the viable cell populations of the urease producing bacteria that elevate the urinary pH and trigger crystal formation.     

Why are Foley catheters so vulnerable to encrustation and blockage by crystalline bacterial biofilm?

Many patients undergoing long-term bladder catheterisation experience blockage and encrustation of their catheters. The problem stems from infection by urease producing bacteria, particularly Proteus mirabilis. Bacterial biofilms colonise the catheters, the activity of urease raises the pH and induces the deposition of calcium and magnesium phosphate crystals. In this study, a laboratory model of the catheterised bladder has been used to examine the early stages in the formation of the crystalline biofilms. The results show that initial cell adhesion is to the irregular surfaces surrounding the catheter eye-holes. Microcolonies form in depressions in these surfaces and spread to cover the entire surface of the rims around the eye-holes. Crystals then form around the bacterial populations and the biofilm starts to move down the lumenal surfaces of the catheters. The encrustation develops most extensively and generally blocks the catheter at or just below the eye-hole. There is a need to improve catheter design and manufacturing procedures for the eye-holes if the problems associated with the current devices are to be reduced.     

Relationship between urease-producing bacteria, urinary pH and encrustation on indwelling urinary catheters

In 11 patients with long-term indwelling catheters the amount of catheter encrustation and urinary pH were measured and the urine regularly cultured over a prolonged period of time (median of 7 periods of 3 weeks). The mean urinary pH was related to the persistent presence of urease-producing micro-organisms (P. mirabilis) and urinary pH governed the precipitation of catheter encrustation. The critical pH appeared to be around 6.8. In patients with a mean urinary pH below this level the encrustation was minute (less than or equal to 2.9 mg phosphate). In patients with a mean urinary pH above 6.8 it was considerable but with a marked interindividual variation (35.5-138.7 mg phosphate). The composition of the encrustation was also strongly pH-related, with a much higher proportion present as magnesium ammonium phosphate in patients with a mean urinary pH above 6.8. The persistent presence of urease producers was not associated with a high pH or a more pronounced precipitation of phosphate in all patients. The amount of encrustation thus appears to depend not only on the presence of urease-producing micro-organisms but also on individual factors such as urinary composition.     

Accuracy of predicting bladder stones based on catheter encrustation in individuals with spinal cord injury

BACKGROUND: Bladder calculi are the second most common urological complication in those with spinal cord injury (SCI). Detection and removal of bladder stones are important to prevent possible complications. OBJECTIVE: To determine the accuracy of bladder stone detection based on catheter encrustation in asymptomatic individuals with SCI. DESIGN: Prospective cohort study. METHODS: Cystoscopy findings in persons with SCI who were noted to have catheter encrustation at the time of catheter removal for their scheduled cystoscopy were used in this prospective study. Indwelling catheters were examined for encrustation at the time of removal as they were being prepared for cystoscopy. Cystoscopy was performed, and the presence or absence of bladder stones was noted. MAIN OUTCOME MEASURES: Presence or absence of bladder stones detected with cystoscopy in those with precystoscopy catheter encrustation. RESULTS: Forty-nine individuals with indwelling catheters were evaluated. Overall, 17/49 (35%) individuals in this study had bladder stones. Catheter encrustation was noted in 13 patients. Of these 13 patients, 11 also had bladder stones. In other words, a positive result for catheter encrustation had a positive result for bladder stones 85% of the time. Thirty-six individuals had no catheter encrustation. Of these, 6 (16%) were found to have bladder stones. CONCLUSIONS: Encrustation of a catheter is highly predictive of the presence of bladder stones. This suggests that cystoscopy should be scheduled in a person undergoing a catheter change if catheter encrustation is noted.     

Factors affecting crystal precipitation from urine in individuals with long-term urinary catheters colonized with urease-positive bacterial species

Weekly urinalysis was conducted for 12 weeks on a group of 21 long-term catheter users with confirmed catheter encrustation and urinary tract colonization with urease-positive bacteria, in order to explore the cause of considerable variation in the severity of encrustation between sufferers. The rapidity of catheter blockage correlated significantly with the pH above which crystals precipitated from urine (the nucleation pH) but not the pH of the voided urine itself. Linear regression showed the nucleation pH to be significantly predicted by a combination of urinary calcium and magnesium concentrations, with calcium being the more influential variable. Reducing the rate of catheter encrustation could be achieved by lowering the urinary concentration of calcium and magnesium, which may only require catheter users to increase their fluid intake.     

The management of indwelling catheters.

Eighteen geriatric patients with indwelling catheters were observed for a total of 393 weekly urine specimens. The effects of a 1 week course of antibiotics/chemotherapeutic agent followed by urinary antiseptics for 6 weeks, and also of regular bladder washouts, were noted. All urine specimens were infected except 24% during antibiotic treatment and 9% during antiseptics and 6% after washouts. Only washouts reduced the extent of catheter blockage. There was little difference in the time in situ between silastic and latex Foley catheters--only 31% of silastic remaining for longer than 4 weeks. Bard-Roberts catheters were the least satisfactory. Catheter leakage was not affected by urinary pH. Further development in long-term catheter management are needed.     

The electrified catheter

Summary A catheter was designed to decrease the incidence of catheter-induced urinary infections. A randomized, controlled study was performed to assess its safety and efficacy. The study comprised 24 patients subjected to hemorrhoidectomy. The criteria for entry were a preoperative urinary pathogen count below 10⁵ colony-forming units/ml urine as well as postoperative urinary retention that did not respond to conservative measures. The 24 patients were randomly assigned to treatment using a Nelaton catheter in 12 patients and an electrified catheter in the remaining 12. The catheters were left in place for 3 days, during which cephalosporin was given parenterally. The electrified catheter (EC) carried two silver-silver chloride electrodes. During the 3 days of catheterization and for 4 days thereafter, daily urine samples were cultured. The criterion for catheter-induced urinary infection was a pathogen count above 10⁵ colony-forming units/ml urine. No complication was encountered from catheterization. Electrodes were not broken. A bacterial count above 10⁵ colony-forming units was found in 7 of 12 patients in the Nelaton catheter group, and a count below 10⁵ units was determined in the 12 patients in the EC group. The study demonstrated that the EC can decrease the incidence of catheter-induced urinary infections. The EC is safe, cost-effective, and without complications.     

A method to minimize indwelling catheter calcification and bladder stones in individuals with spinal cord injury

Indwelling catheters are a common tool of bladder management in persons with high-level spinal cord injury who are unable to intermittently catheterize their bladders. Indwelling catheters are used to prevent bladder overdistension, which can trigger autonomic dysreflexia in those with injuries at or above T6. Unfortunately, indwelling catheters are prone to encrustation and can lead to the formation of bladder stones that can block the catheter and cause autonomic dysreflexia. We found that weekly catheter changes dramatically reduced catheter encrustation and stones in 2 individuals who had a history of recurrent stones despite various accepted interventions. We describe the clinical course and impact of this method in each case.     

Assessment of the use of bladder washouts/instillations in patients with long-term indwelling catheters.

A randomised cross-over study of 3 bladder washout treatments--saline, Suby G and Solution R--was conducted on 25 elderly females with long-term catheters in order to examine crystal formation and catheter encrustation. With 2 exceptions, all patients produced crystals; only 14 completed the study. While a significant reduction in struvite crystals was found in the returned acidic washout fluid, there was no significant reduction of crystals in the neutral (saline) washout following any of the 3-week periods of treatment. Uric acid crystals appeared with Suby G and Solution R and these solutions were associated with higher red cell deposits in the urine. There was no significant difference in catheter encrustation between the various washouts.     

Swarming of Proteus mirabilis over ureteral stents: a comparative assessment

BACKGROUND AND PURPOSE: Encrustation on indwelling ureteral stents is commonly related to the presence of urease-producing bacteria that elevate the pH of the urine through the hydrolysis of urea, resulting in the precipitation of calcium and magnesium salts. Using a model previously shown to measure accurately the ability of Proteus mirabilis to swarm over catheter surfaces (Eur J Clin Microbiol Infect Dis 1999;18:206), we investigated the ability of this organism to swarm over three ureteral stents with potential encrustation-resistance properties. MATERIALS AND METHODS: Three commercially available ureteral stents were selected for evaluation: a low surface-energy stent, a hydrogel-coated stent, and a silicone stent. Ten-microliter aliquots of a 4-hour culture of P. mirabilis 296 in Trypticase soya (TSA) broth was inoculated 5 mm from a 1-cm channel cut out from TSA plates. Ten-millimeter stent sections were placed as bridges across the central channel adjacent to the inocula. Time to pathogen crossing was measured. RESULTS: The mean time (+/- SD) to pathogen migration across the three test materials was 15.9 +/- 6.1, 19.8 +/- 9.5, and 29.7 +/- 14.3 hours for the low surface-energy, hydrogel-coated, and silicone stents, respectively. Statistical analysis revealed significant differences between the crossing times of the low surface-energy (P = 0.001) and hydrogel-coated (P = 0.034) stents compared with silicone but not between the low surface-energy and hydrogel-coated stents (P = 0.387). CONCLUSION: Migration of P. mirabilis 296 across silicone stents was significantly reduced compared with low surface-energy and hydrogel-coated stents. These findings suggest that P. mirabilis may have a lower affinity for silicone stents, which may translate into a reduced risk of infection with P. mirabilis and associated stent encrustation.     

Bacterial biofilms in patients with indwelling urinary catheters

Bacteria have a basic survival strategy: to colonize surfaces and grow as biofilm communities embedded in a gel-like polysaccharide matrix. The catheterized urinary tract provides ideal conditions for the development of enormous biofilm populations. Many bacterial species colonize indwelling catheters as biofilms, inducing complications in patients' care. The most troublesome complications are the crystalline biofilms that can occlude the catheter lumen and trigger episodes of pyelonephritis and septicemia. The crystalline biofilms result from infection by urease-producing bacteria, particularly Proteus mirabilis. Urease raises the urinary pH and drives the formation of calcium phosphate and magnesium phosphate crystals in the biofilm. All types of catheter are vulnerable to encrustation by these biofilms, and clinical prevention strategies are clearly needed, as bacteria growing in the biofilm mode are resistant to antibiotics. Evidence indicates that treatment of symptomatic, catheter-associated urinary tract infection is more effective if biofilm-laden catheters are changed before antibiotic treatment is initiated. Infection with P. mirabilis exposes the many faults of currently available catheters, and plenty of scope exists for improvement in both their design and production; manufacturers should take up the challenge to improve patient outcomes.