Biomaterial modification of urinary catheters with antimicrobials to give long-term broadspectrum antibiofilm activity

Catheter-associated urinary tract infection (CAUTI) is the commonest hospital-acquired infection, accounting for over 100,000 hospital admissions within the USA annually. Biomaterials and processes intended to reduce the risk of bacterial colonization of the catheters for long-term users have not been successful, mainly because of the need for long duration of activity in flow conditions. Here we report the results of impregnation of urinary catheters with a combination of rifampicin, sparfloxacin and triclosan. In flow experiments, the antimicrobial catheters were able to prevent colonization by common uropathogens Proteus mirabilis, Staphylococcus aureus and Escherichia coli for 7 to 12 weeks in vitro compared with 1–3 days for other, commercially available antimicrobial catheters currently used clinically. Resistance development was minimized by careful choice of antimicrobial combinations. Drug release profiles and distribution in the polymer, and surface analysis were also carried out and the process had no deleterious effect on the mechanical performance of the catheter or its balloon. The antimicrobial catheter therefore offers for the first time a means of reducing infection and its complications in long-term urinary catheter users

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

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

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

Observations on the adherence of Proteus mirabilis onto polymer surfaces.

Aims:  Infection of the catheterized urinary tract with Proteus mirabilis causes blockage of the catheter by crystalline bacterial biofilms. The aim of this work is to identify a surface-coating for catheters that is not vulnerable to colonization by Pr. mirabilis. Methods and Results:  A parallel-plate flow-cell and phase contrast microscopy were used to follow bacterial adhesion onto polymer films. Experiments with a urease-negative mutant of Pr. mirabilis suspended in buffer or urine, identified agarose as a polymer on which biofilm did not form. In tests with wild-type urease-producing cells in urine, no adhesion of cells onto agarose was observed for 3 h but then as the pH rose above 8·2, the surface rapidly became colonized by crystalline biofilm. Conclusions:  In urine at pH below 8·0, Pr. mirabilis does not adhere to agarose-coated surfaces. When the pH rises above 8·2, however, aggregates of crystals and bacteria form in the urine and are deposited on such surfaces. Significance and Impact of the Study:  Strategies to prevent the formation of crystalline biofilms on urinary catheters will need to consider both the properties of the surface-coatings and the requirement to prevent the alkaline conditions that induce crystal formation in urine