Clinical complications of urinary catheters caused by crystalline biofilms: something needs to be done.

This review is largely based on a previous paper published in the journal Spinal Cord. The care of many patients undergoing long-term bladder catheterization is complicated by encrustation and blockage of their Foley catheters. This problem stems from infection by urease-producing bacteria, particularly Proteus mirabilis. These organisms colonize the catheter forming an extensive biofilm; they also generate ammonia from urea, thus elevating the pH of urine. As the pH rises, crystals of calcium and magnesium phosphates precipitate in the urine and in the catheter biofilm. The continued development of this crystalline biofilm blocks the flow of urine through the catheter. Urine then either leaks along the outside of the catheter and the patient becomes incontinent or is retained causing painful distension of the bladder and reflux of urine to the kidneys. The process of crystal deposition can also initiate stone formation. Most patients suffering from recurrent catheter encrustation develop bladder stones. P. mirabilis establishes stable residence in these stones and is extremely difficult to eliminate from the catheterized urinary tract by antibiotic therapy. If blocked catheters are not identified and changed, serious symptomatic episodes of pyelonephritis, septicaemia and endotoxic shock can result. All types of Foley catheters including silver- or nitrofurazone-coated devices are vulnerable to this problem. In this review, the ways in which biofilm formation on Foley catheters is initiated by P. mirabilis will be described. The implications of understanding these mechanisms for the development of an encrustation-resistant catheter will be discussed. Finally, the way forward for the prevention and control of this problem will be considered.

Imaging the in-plane magnetization in a Co microstructure by Fourier transform holography.

We report on experiments using Fourier transform holography to image the in-plane magnetization of a magnetic microstructure. Magnetic sensitivity is achieved via the x-ray magnetic circular dichroism effect by recording holograms in transmission at off-normal incidence. The reference beam is defined by a narrow hole milled at an inclined angle into the opaque mask. We present magnetic domain images of an in-plane magnetized cobalt element with a size of 2 µm × 2 µm× 20 nm. The domain pattern shows a multi-vortex state that deviates from the simple Landau ground state.

The encrustation and blockage of long-term indwelling bladder catheters: a way forward in prevention and control.

OBJECTIVES: To review the literature showing that understanding how Foley catheters become encrusted and blocked by crystalline bacterial biofilms has led to strategies for the control of this complication in the care of patients undergoing long-term indwelling bladder catheterization. METHODS: A comprehensive PubMed search of the literature published between 1980 and December 2009 was made for relevant articles using the Medical Subject Heading terms 'biofilms', 'urinary catheterization', 'catheter-associated urinary tract infection' and 'urolithiasis'. Papers on catheter-associated urinary tract infections and bacterial biofilms collected during 40 years of working in the field were also reviewed. RESULTS: There is strong experimental and epidemiological evidence that infection by Proteus mirabilis is the main cause of the crystalline biofilms that encrust and block Foley catheters. The ability of P. mirabilis to generate alkaline urine and to colonize all available types of indwelling catheters allows it to take up stable residence in the catheterized tract in bladder stones and cause recurrent catheter blockage. CONCLUSION: The elimination of P. mirabilis by antibiotic therapy as soon as it appears in the catheterized urinary tract could improve the quality of life for many patients and reduce the current expenditure of resources when managing the complications of catheter encrustation and blockage. For patients who are already chronic blockers and stone formers, antibiotic treatment is unlikely to be effective owing to the resistance of cells in the crystalline biofilms. Strategies such as increasing fluid intake with citrated drinks could control the problem until bladder stone removal can be organized.

Complicated catheter-associated urinary tract infections due to Escherichia coli and Proteus mirabilis.

Catheter-associated urinary tract infections (CAUTIs) represent the most common type of nosocomial infection and are a major health concern due to the complications and frequent recurrence. These infections are often caused by Escherichia coli and Proteus mirabilis. Gram-negative bacterial species that cause CAUTIs express a number of virulence factors associated with adhesion, motility, biofilm formation, immunoavoidance, and nutrient acquisition as well as factors that cause damage to the host. These infections can be reduced by limiting catheter usage and ensuring that health care professionals correctly use closed-system Foley catheters. A number of novel approaches such as condom and suprapubic catheters, intermittent catheterization, new surfaces, catheters with antimicrobial agents, and probiotics have thus far met with limited success. While the diagnosis of symptomatic versus asymptomatic CAUTIs may be a contentious issue, it is generally agreed that once a catheterized patient is believed to have a symptomatic urinary tract infection, the catheter is removed if possible due to the high rate of relapse. Research focusing on the pathogenesis of CAUTIs will lead to a better understanding of the disease process and will subsequently lead to the development of new diagnosis, prevention, and treatment options.

Magnetic ground state of single and coupled permalloy rectangles.

We have studied the magnetic domain structure in Permalloy rectangles that reveal flux-closure domain configurations. Arrays with varying spacing between the rectangles are investigated by scanning electron microscopy with polarization analysis as well as by micromagnetic simulation. In contrast to general expectation, rectangles in the flux-closure Landau state show significant coupling and form a magnetic pattern of common chirality. The coupling is due to the stray field that originates from small changes of the magnetization alignment, which is sensitive to the exact shape and the separation of the rectangles.

Observations on the development of the crystalline bacterial biofilms that encrust and block Foley catheters.

The care of many patients undergoing long-term bladder catheterisation is complicated when the flow of urine through the catheter is blocked by encrustation. The problem results from infection by urease-producing bacteria, especially Proteus mirabilis, and the subsequent formation of crystalline biofilms on the catheter. The aim of this study was to discover how P. mirabilis initiates the development of these crystalline biofilms. The early stages in the formation of the biofilms were observed on a range of Foley catheters in a laboratory model of the catheterised bladder. Scanning electron micrographs revealed that when all-silicone, silicone-coated latex, hydrogel-coated latex, hydrogel/silver-coated latex and nitrofurazone silicone catheters were inserted into bladder models containing P. mirabilis and alkaline urine, their surfaces were rapidly coated with a microcrystalline foundation layer. X-ray microanalysis showed that this material was composed of calcium phosphate. Bacterial colonisation of the foundation layer followed and by 18h the catheters were encrusted by densely populated crystalline P. mirabilis biofilms. These observations have important implications for the development of encrustation-resistant catheters. In the case of silver catheters for example, bacterial cells can attach to the crystalline foundation layer and continue to grow, protected from contact with the underlying silver. If antimicrobials are to be incorporated into catheters to prevent encrustation, it is important that they diffuse into the urine and prevent the rise in pH that triggers crystal formation.

Biofilms.

Outside of the laboratory, most microbes grow as organised biofilm communities on surfaces. The past year has seen important advances in our understanding of how cells initiate biofilm formation. We have also begun to appreciate how cells can co-ordinate their activities and build the complex structures of mature biofilms that afford protection for their inhabitants.

Role of swarming in the formation of crystalline Proteus mirabilis biofilms on urinary catheters.

The care of many patients undergoing long-term bladder catheterization is frequently complicated by infection with Proteus mirabilis. These organisms colonize the catheter, forming surface biofilm communities, and their urease activity generates alkaline conditions under which crystals of magnesium ammonium phosphate and calcium phosphate are formed and become trapped in the biofilm. As the biofilm develops it obstructs the flow of urine through the catheter, causing either incontinence due to leakage of urine around the catheter or retention of urine in the bladder. The aim of this study was to investigate the role of the surface-associated swarming motility of P. mirabilis in the initiation and development of these crystalline catheter biofilms. A set of stable transposon mutants with a range of swimming and swarming abilities were tested for their ability to colonize silicone surfaces in a parallel-plate flow cell. A laboratory model of the catheterized bladder was then used to examine their ability to form crystalline, catheter-blocking biofilms. The results showed that neither swarming nor swimming motility was required for the attachment of P. mirabilis to silicone. Mutants deficient in swarming and swimming were also capable of forming crystalline biofilms and blocking catheters more rapidly than the wild-type strain.

MuSK-antibody positive myasthenia gravis: clinical and electrodiagnostic patterns.

OBJECTIVE: To examine the clinical manifestations and patterns of electromyographic abnormalities in MuSK-Ab positive myasthenia gravis. METHODS: The clinical evaluations and electrodiagnostic testing results of 20 MuSK-Ab positive myasthenia gravis patients were retrospectively reviewed and compared with matched AChR-Ab positive (N = 72) and MuSK-Ab negative/AChR-Ab negative (N = 24) patients. RESULTS: MuSK-Ab positive patients were younger and more frequently female and African-American, and compared to the AChR-Ab positive patients, were more likely to present with respiratory symptoms or neck extension weakness. MuSK-Ab positive patients were less likely to have abnormal jitter in a limb muscle: only 59% had abnormal jitter in the extensor digitorum communis muscle, compared to 80% of the AChR-Ab negative/MuSK-negative patients and 91% of the AChR-Ab positive patients. CONCLUSIONS: Our MuSK-Ab positive patients not only differ demographically from our MuSK-Ab negative cohort, but they also appear to have a more limited distribution of SFEMG abnormalities. SIGNIFICANCE: The possibility that electrophysiologic abnormalities may not be widely distributed should be considered during electrodiagnostic evaluation of suspected MuSK-Ab positive MG and in selecting muscles for molecular, morphologic, or microphysiologic studies in this condition.

Reduced adherence of Candida to silane-treated silicone rubber.

Silicone rubber is widely used in the construction of medical devices that can provide an essential role in the treatment of human illness. However, subsequent microbial colonization of silicone rubber can result in clinical infection or device failure. The objective of this study was to determine the effectiveness of a novel silane-treated silicone rubber in inhibiting microbial adherence and material penetration. Test material was prepared by a combination of argon plasma discharge treatment and fluorinated silane coupling. Chemicophysical changes were then confirmed by X-ray photoelectron spectroscopy, contact-angle measurement, and atomic force microscopy. Two separate adherence assays and a material penetration assay assessed the performance of the new material against four strains of Candida species. Results showed a significant reduction (p < 0.01) of Candida albicans GDH 2346 adherence to silane-treated silicone compared with untreated controls. This reduction was still evident after the incorporation of saliva into the assay. Adherence inhibition also occurred with Candida tropicalis MMU and Candida krusei NCYC, although this was assay dependent. Reduced penetration of silane-treated silicone by Candida was evident when compared to untreated controls, plaster-processed silicone, and acrylic-processed silicone. To summarize, a novel silicone rubber material is described that inhibits both candidal adherence and material penetration. The clinical benefit and performance of this material remains to be determined.

Bladder management and urinary tract infections in Danish hospitals, nursing homes, and home care: a national prevalence study.

OBJECTIVE: To establish the prevalence of urinary tract infection in patients undergoing various forms of bladder management. DESIGN: A nationwide descriptive point-prevalence survey with logistic regression analysis of the data relating infection to bladder management. SETTING: Fifteen hospitals, 21 nursing homes, and 13 home care districts throughout Denmark. PATIENTS: Information was collected on 3,665 patients. On the day of the study, 349 patients had indwelling catheters and 1,150 were using external urine drainage systems (condoms or diapers) for bladder management. RESULTS: The prevalence of urinary tract infections in catheterized patients and those using external drainage systems was 13.2% and 8.1%, respectively. The prevalence of hospital-acquired urinary tract infection (4.2%) had not changed from that reported in 1978. The proportion of these infections related to the indwelling catheter, however, had reduced from 66% to 30%. Logistic regression analysis confirmed that, when corrected for the patient-related confounders (female gender, age > 60 years, incontinence, immobility, and stay in hospital for longer than 15 days), condoms (odds ratio [OR], 5.94; 95% confidence interval [CI95], 2.8 to 12.5), indwelling catheters (OR, 3.3; CI95, 2.3 to 4.8), and diapers (OR, 1.5; CI95, 1.1 to 2.1) were significantly (P < .001, P < .001, and P = .008, respectively) related to infection. CONCLUSIONS: Prevalence surveys have revealed that over the period 1978 to 1991, during which efforts have been made to restrict the use of indwelling catheters and to encourage the care of catheterized patients according to guidelines recommended by the Danish National Centre for Hospital Hygiene, the percentage of hospital-acquired urinary tract infections associated with indwelling catheters has been halved. External urine drainage systems, however, have emerged as significant risk factors for urinary tract infection.

Racial differences in optic nerve head parameters.

Results of previous studies have strongly indicated that the prevalence of elevated intraocular pressure is greater in blacks than in whites and that blacks are more susceptible than whites to glaucomatous damage at any given level of pressure. It has also been suggested that a larger disc area might predispose an eye to glaucomatous damage. We investigated the possibility that clinically quantifiable differences might exist in optic disc parameters between normotensive white and black patients. Disc area, cup-to-disc ratio, and cup volume measured with a video-ophthalmograph (Rodenstock Optic Disc Analyzer) were significantly larger in blacks than in whites, while there was no difference in the disc rim area between the two groups. We derived a mathematical model of the optic disc that relates posterior displacement of the lamina cribrosa to the disc area, distensibility of the disc, and intraocular pressure.

Chlorhexidine resistance in Proteus mirabilis.

A total of 104 clinical isolates of Pr. mirabilis from three hospitals were screened for their sensitivity to chlorhexidine. The minimum inhibitory concentrations of the antiseptic for these strains ranged from 10 to 800 mug/ml. Two strains sensitive to 20 mug of chlorhexidine/ml were adapted to resistance by growth in subinhibitory concentrations of the antiseptic, their MIC values increasing to 200 and 800 mug/ml. These derived strains exhibited slightly reduced sensitivity to cetrimide and benzalkonium chloride. The chlorhexidine-resistant clinical isolates also exhibited this partially decreased sensitivity to the quaternary ammonium compounds. Both the chlorhexidine-sensitive and -resistant strains were uniformly sensitive to chloroxylenol (Dettol), glutaraldehyde, and 2-phenoxyethanol.

Sensitivity of Providence to antiseptics and disinfectants.

Seventy isolates of Providence were obtained from urinary tract infections in patients from five hospitals. They were all identified as Providence B (Providencia stuartii). A typing system was devised for these organisms based on their production of and sensitivity to bacteriophage and bacteriocins. Using this system, 27 distinct strains were recognized, and it was clear that many patients had been infected with the same strain. The minimum inhibitory concentrations of six antiseptics and disinfectants for these strains were determined. Many of the strains were up to 300-fold more resistant to the cationic antiseptics chlorhexidine, cetrimide, and Resiguard than the control strain Escherichia coli NCTC 10418. The sensitivities of the Providence strains to Hycolin, glutaraldehyde, and phenyl mercuric nitrate, however, were similar to those of the control organism. There were significant correlations between the sensitivities of the strains to the three cationic antiseptics. The loss of chlorhexidine resistance from a Providence strain after exposure of the cells to N-methyl-N' nitro N nitrosoguanidine resulted in a concomitant loss of resistance to cetrimide and Resiguard, but there was no significant increase in the sensitivity of the mutants to the other three antibacterials.

Antiseptic and antibiotic resistance in Gram-negative bacteria causing urinary tract infection.

A collection of 802 isolates of Gram-negative bacteria causing urinary tract infections was made from general practice, antenatal clinics, and local hospitals. The organisms were tested for their sensitivity to chlorhexidine, cetrimide, glutaraldehyde, phenyl mercuric nitrate, a phenolic formulation, and a proprietary antiseptic containing a mixture of picloxydine, octyl phenoxy polyethoxyethanol, and benzalkonium chloride. Escherichia coli, the major species isolated, proved to be uniformly sensitive to these agents. Approximately 10% of the total number of isolates, however, exhibited a degree of resistance to the cationic agents. These resistant organisms were members of the genera Proteus, Providencia, and Pseudomonas; they were also generally resistant to five, six, or seven antibiotics. It is proposed therefore that an antiseptic policy which involves the intensive use of cationic antiseptics might lead to the selection of a flora of notoriously drug-resistant species.

Sensitivity of urine-grown cells of Providencia stuartii to antiseptics.

Urine-grown cultures of 23 clinical isolates of Gram-negative bacteria having a range of minimum inhibitory concentration values for chorhexidine were challenged with various concentrations of this antiseptic. The results suggest that cells of Providencia stuartii, in particular, exhibit a considerable degree of resistance to chlorhexidine under these conditions, concentrations of up to 10 000--20 000 microgram/ml of urine being necessary to produce complete loss of viability of such cultures. Of the other two antiseptics tested, phenoxyethanol proved to be the more effective, the recommended use concentration of 2% v/v producing reductions in viable counts of greater than six logarithms in all the strains examined. It is suggested that phenoxyethanol may be a suitable alternative to the cationic agents for use in antiseptic policies for bladder management of urinary tract infections with Providencia stuartii.

Evidence of autoinducer activity in naturally occurring biofilms.

N-Acyl homoserine lactone (AHL) molecules have been shown to act as mediators of population density-dependent (quorum-sensing) gene expression in numerous Gram-negative bacteria. Functions associated with AHL include light production in Vibrio fischeri, expression of virulence factors in Pseudomonas aeruginosa, and conjugation in Agrobacterium tumefaciens. In nature, bacteria often grow as surface-adherent biofilm communities. As biofilms typically contain high concentrations of cells, AHL activity and quorum-sensing gene expression have been proposed as essential components of biofilm physiology. However, proof of AHL production within biofilms has heretofore been lacking. In this study we have employed a cross-feeding assay, using A, tumefaciens A136 (traI::lacZ) as an AHL-responsive reporter strain, to show the presence of naturally occurring AHL production in aquatic biofilms growing on submerged stones. AHL was detected in living biofilms and biofilm extracts, but was not present in rocks lacking a biofilm. This represents the first report of AHL activity in naturally occurring biofilms.

Strategies for the control of catheter encrustation.

Two general strategies have been adopted to develop catheter materials that resist encrustaion by bacterial biofilms: (a) the incorporation of antimicrobial agents into the polymers and (b) the production of materials with surface properties which prevent the adherence of bacterial cells. Our experience to develop non-adherent surfaces which abstracts design from nature is reported. Compounds based on 2-methacryloloxyethylphosphorylcholine co-polymerised with long-chain alkyl methacrylates have been produced which have structural and surface properties similar to those of the outer membranes of erythrocytes. These PC-coatings have been applied onto catheter base materials where they produce polar surfaces that are extremely hydrophilic. In experiments using a laboratory model of the catheterised bladder we found that the PC-coatings did not reduce colonisation of latex or silicone catheters by crystalline Proteus mirabilis biofilm. There were no significant difference between the amounts of calcium and magnesium salts deposited on coated and non-coated catheters. In a further set of experiments the PC-coatings did not significantly increase the mean times for which catheters drained freely. In a parallel clinical study, the performance of PC-coated ureteral stents was investigated. Scanning electron microscopy and bacteriological analysis on 44 PC-coated stents that had been implanted in patients for 12-week periods and 28 control stents suggested that the PC-coated devices were less vulnerable to encrustation and colonisation by bacterial biofilm than normal stents. It was of interest that in contrast to encrusted catheters, urease producing species such as P. mirabilis were rarely isolated from the stents. The main organisms colonising the stents were enterococci and coagulase-negative staphylococci. These results suggest that the mechanisms of catheter and stent encrustation may be different and require different strategies for control.

An assessment of antiseptic bladder washout solutions using a physical model of the catheterized bladder.

The antibacterial activity of six antiseptic solutions formulated for use in bladder washout procedures has been examined in a simple model of the catheterized bladder. The experiments were carried out under conditions which examined the efficacy of the formulations against organisms that had recently contaminated the bladder urine. At cell densities of 10(4) cfu ml-1 all the solutions tested proved effective in eliminating bacteria from the bladder urine. Under conditions simulating heavy contamination (10(7)-10(8) cfu ml-1) however, only mandelic acid (1% w/v) eliminated the range of bacterial species commonly responsible for catheter-associated urinary tract infection.

Encrustation of indwelling urethral catheters by Proteus mirabilis biofilms growing in human urine.

The encrustation and blockage of four types of urinary catheters was studied in a simple laboratory model of the catheterized bladder. Pooled human urine was supplied to the bladder chamber at 0.5 mL/min. The bladder urine was inoculated with a clinical strain of Proteus mirabilis that had been isolated from an encrusted catheter. The models were operated until the catheters blocked and atomic absorption spectrometry was used to assess the amounts of calcium and magnesium deposited on the catheters. Scanning electron microscopy was also used to locate and assess the degree of encrustation. All catheters blocked rapidly, the mean times to blockage ranging from 17.7 h (silver-coated latex), 34 h (hydrogel-coated latex), 38 h (silicone-coated latex) to 47 h (all silicone). The internal diameters of the latex catheters were only 1.5 mm compared to the 2.5 mm of the all-silicone catheters. The calcium and magnesium salts were deposited on the lumenal surfaces along the full length of catheters but occurred most extensively just below the eye-holes. There is clearly a need to develop catheter surfaces which resist encrustation by crystalline biofilms of P. mirabilis.