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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.

(1996). Bacterial biofilms and the encrustation of urethral catheters. Biofouling: Vol. 9, No. 4, pp. 293-305.

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. 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. 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. 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.

Urinary catheters are indwelling medical devices used in both the nosocomial and nursing home settings for relief of urinary retention and incontinence. Due to the frequent- and sometimes unnecessary-use of indwelling catheters in these settings (circa 21–50% of patients), many individuals are placed at risk from sequelae associated with catheter placement. The most notable complication associated with indwelling urinary catheters is the development of nosocomial urinary tract infections (UTIs) known as catheter-associated UTIs (CAUTIs). Over one million CAUTI cases per annum are recorded in the United States; this represents greater than 40% of all nosocomial infections. Both the presence of the catheter itself and the nosocomial setting predispose individuals to CAUTIs. CAUTIS may be caused by a number of etiological agents; the most common of these being Escherichia coli and Proteus mirabilis. Microorganisms isolated less commonly from CAUTIs include Staphylococcus aureus, Klebsiella spp., Pseudomonas spp. and Enterobacter spp. Regardless of the genus, pathogens wishing to survive within the environment of the catheterized urinary tract must possess essential virulence factors including, most importantly, those related to adherence to the catheter itself. This chapter seeks to set out in detail the nature of these virulence factors.

SUMMARY 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.

SUMMARYSixty-one isolates ofAeromonasspp. from the faeces of pigs, cows and a variety of associated environmental sources were examined for the characteristics that are reputed to have roles in pathogenicity. Most isolates ofAeromonas hydrophilawere cytotoxic (96·4%) and were capable of producing cell elongation factor (75%) and haemagglutinins (67·9%). In contrast few of theAeromonas caviaeisolates produced these three markers (13·6 %, 27·3% and 36·4% respectively). In general,Aeromonas sobriaoccupied an intermediate position (36·4%, 27·3% and 54·5%), but they did produce the highest mean invasion index for HEp-2 cells. Statistical analysis revealed significant associations between the carriage of these factors and it was clear that many isolates of aeromonads from water and animals possessed the full battery of putative virulence factors.

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.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.Control catheters blocked in mean times ranging from 18 to 27 h. The pH of the urine rose from 6.1 to8.6. 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.Inflating the retention balloons with triclosan could have practical applications in controlling encrustation on both latex and silicone-based catheters.

Bacteria resistant to both the agents deployed to prevent infections and those used to treat infections would be formidable nosocomial pathogens. The aim of this paper is to review the evidence that gram-negative bacteria resistant to antibiotics and biocides have emerged and been responsible for catheter-associated urinary tract infection. A study of patients undergoing intermittent bladder catheterization revealed that the frequent application of the antiseptic chlorhexidine to the perineal skin prior to the insertion of the catheter was effective against the normal gram-positive skin flora but not against the gram-negative organisms that subsequently colonized this site. Organisms such as Providencia stuartii, Pseudomonas aeruginosa and Proteus mirabilis were repeatedly isolated from the skin of these patients and inevitably went on to cause urinary infections. The minimum inhibitory concentration (MIC) of chlorhexidine for many of these strains proved to be 200-800 microg ml(-1) compared with the 10-50 microg ml(-1) recorded for reference strains of gram-negative species. A subsequent survey of over 800 gram-negative isolates from urinary tract infections in patients from both hospitals and the community revealed that chlorhexidine resistance was not a widespread phenomenon, but was restricted to these species and to units where the care of catheterized patients involved the extensive use of chlorhexidine. Analysis of the antibiotic resistance patterns revealed that the chlorhexidine-resistant strains were also multidrug resistant. Other clinical studies also reported catheter-associated infections with chlorhexidine- and multidrug-resistant strains of Pr. mirabilis when chlorhexidine was being used extensively. This species poses particular problems to the catheterized patient. Chlorhexidine thus proved counterproductive in the care of catheters and its use in this context has been largely abandoned. Suggestions of reintroducing this agent in the form of biocide-impregnated catheters should be resisted.

To examine the ability of organisms that infect the catheterized urinary tract to migrate over the surfaces of Foley catheters.In a simple laboratory model, organisms were challenged to migrate across sections of hydrogel-coated latex, hydrogel/silver-coated latex, silicone-coated latex and all-silicone catheters. The sections (1 cm long) were placed as bridges in channels between blocks of agar and the test organisms inoculated onto the agar adjacent to one side of each bridge. The plates were incubated at 37 degrees C for 24 h and examined for growth of the test organisms on the agar on the other side of the bridges. A collection of swarming, swimming and nonmotile species were tested in the model. The relative mobilities of the test organisms were expressed as migration indices, calculated as the percentage of tests in which bacterial migration was observed over each type of catheter bridge.The swarmer cells of Proteus mirabilis and P. vulgaris migrated successfully (migration indices of 73-100) over all four types of catheter. The migration index of Serratia marcescens swarmers was reduced to 33 over the silver-coated catheters, but these cells crossed over the other catheter surfaces with ease (indices of 100). Pseudomonas aeruginosa was the most mobile of the swimming, non-swarming organisms with indices of 70-22, but this group was less capable of migration than the swarmers. Indices were 0-33 for nonmotile organisms. The mean migration indices for the nine species for each type of catheter were 57 (hydrogel-coated latex), 49 (silver/hydrogel-coated latex), 41 (silicone-coated latex) and 35 (all-silicone). The swarmer cells of P. mirabilis moved through populations of Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis, and then migrated over sections of hydrogel-coated latex catheters with little or no reduction in migration index. They were also capable of transporting the nonmotile cells of K. pneumoniae and S. aureus over the catheters. The migration index of P. mirabilis swarmers was substantially reduced in the presence of Ps. aeruginosa and S. marcescens.Hydrogel coatings facilitate the migration of urinary tract pathogens over catheter surfaces. With the exception of S. marcescens, the incorporation of silver into the hydrogel did not inhibit migration. Swarmer cells were particularly effective at moving over catheters and P. mirabilis swarmers were also capable of transporting other species. This suggests that inhibitors of swarming could be useful in controlling catheter-associated infection and the complications resulting from the spread of bacterial biofilm over catheters.

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.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.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. (P0.001). 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 (P0.01) 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 for10 days.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.

An ultrasound-enhanced latex agglutination technique has been applied to the detection of bacteria in urine. The approach combines the use of ultrasound, the dilution of latex to allow agglutination with low levels of antigen, and microscopy. Using commercially available latex coated with antibody to Esch. coli O157 or K1, ultrasound enhanced the detection of Esch. coli strains carrying these antigens by x512 and x2048 respectively, compared with the standard test card procedure. The latex particles in the commercial kits were 0.4-1.0 micron in diameter. As larger particles are more effectively manipulated in a sound field, particles of 2.8 microns diameter were coated with antiserum against a urinary tract isolate of Esch. coli (SP3112). The application of ultrasound with these particles facilitated the detection of 6 x 10(3) cells/mL of Esch. coli SP3112 within 2 min, a10,000-fold increase in sensitivity compared with the normal agglutination procedure. The possible exploitation of this technique in the clinical laboratory for the rapid, sensitive detection of bacterial antigens in urine is discussed.

The activity of three antiseptic bladder washout solutions was examined in a physical model of the catheterized bladder. Tests were performed against cultures of four common urinary tract pathogens that had established themselves in the model and colonized the surfaces with biofilm. Double instillations of chlorhexidine (0.02% w/v) at 6-h intervals failed to eliminate Pseudomonas aeruginosa, Proteus mirabilis, and Providencia stuartii from the bladder model. Escherichia coli, however, was susceptible to a second instillation provided that it was performed within 12 h. Supplementing chlorhexidine with EDTA and TRIS potentiated its activity against E. coli. Mandelic acid (1.0% w/v) was the most effective of the agents, double instillations eliminating all but Pr. mirabilis infections.

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.

SUMMARYReplicate faecal samples from healthy individual pigs and cows were examined for the presence ofAeromonassp. over a 12-month period. Aeromonads were found to be minor components of the faecal flora, only 8·8 % of 520 samples from pigs and 4·6% of 481 samples from cows proving positive. Isolation rates in both groups of animals were seasonal.A. hydrophila(62% of the isolates) was the predominant species in cows, followed byA. caviae(32%) andA. sobria(15%). This pattern was also recorded in the natural waters that the animals drank from during the period when the faecal carriage rate was at its highest. In pigs,A. caviae(59%) was more common thanA. hydrophila(41%).A. sobriawas not found in any of the pig-associated samples. It seems that cattle acquire their faecal aeromonads from drinking water. The source of the organisms in pigs is less clear.

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.

A comparison has been made of the activity of three antiseptics that are used as bladder irrigants in the treatment of urinary tract infection in catheterised patients. At the concentrations and exposure times used for bladder irrigation, phenoxyethanol (2:4% v/v) proved to be highly bactericidal against urine-grown cells of all the common urinary pathogens tested. Chlorhexidine (200 microgram/ml) was active against Escherichia coli and produced significant reductions in the viability of Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa but failed to eradicate Providencia stuartii. Exposure to noxythiolin (2.5% v/v) for 20 min had little effect in any of the bacteria, even though all strains tested had been recorded as noxythiolin-sensitive by conventional plate sensitivity tests. Contact with noxythiolin for periods of at least 1-2 hrs was necessary before extensive bactericidal activity was detected. These results provide an explanation of the poor clinical performance of noxythiolin that we have observed.

The antibiotic policies that have been recommended in the literature for the prevention and treatment of urinary tract infections in patients with spinal cord injuries undergoing long-term intermittent catheterisation are reviewed. Current practices in spinal units in England and Wales are reported and the rational bases of these policies are considered.

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.

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.

The lipid composition of Providencia stuartii has been shown to resemble closely that of Proteus mirabilis. The ability of some Pv, stuartii strains to survive exposure to high concentrations of the antiseptic chlorhexidine could not be explained in terms of differences in lipid content between sensitive and resistant strains. In addition, resistance could not be attributed to either reduced adsorption of the antiseptic or to its gross enzymic degradation.

A selective differential medium has been used to search for Providencia stuartii in sewage, sewage contaminated natural waters and the faeces and skin of a small population of healthy non-hospitalized males. Colonization of 12 male patients with long-term indwelling bladder catheters and the general environment of the spinal injury unit was also examined. Providencia stuartii was not isolated from the non-hospital samples, but colonization of the urine (two patients) faeces (five patients) and skin (eight patients) was observed. Apart from equipment that had been in contact with patients urine or skin there was no general contamination of the ward environment suggesting that colonized patients were the main reservoir of this multiply antibiotic-resistant nosocomial pathogen.

The ability of urinary isolates of nine species of bacteria to bind to urinary catheters has been assessed using a bioluminescence technique. The experiments revealed the particularly adherent properties of Pseudomonas aeruginosa. This organism has also been shown to be most frequently isolated from the urines of the patients undergoing indwelling catheterization. It is suggested that P. aeruginosa commonly grows on the surface of catheters in situ, and that at this site it can survive antibiotic therapy and cause apparent recurrence of infection by reinoculation of the urine once therapy has been completed.