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Eighty percent of urinary tract infections (UTIs) are associated with the presence of a urinary catheter. Alarmingly, patients with a UTI are also three times more likely to die; the fatality rate from urinary tract related bacteraemia is around 13%.^1–6 Infection is due to encrustation of the urinary catheter.⁷ It has been suggested that urinary catheters with smoother drainage apertures are less prone to struvite formation and subsequent catheter encrustation.⁸ It is, therefore, advisable that catheters are manufactured with perfectly smooth surfaces and apertures to reduce the potential for infection. An ultrasonic cutting technology is described here that produces smooth apertures and eliminates problems associated with debris.

The clinical problem

Figure 1: Each row shows images of the mechanical cut apertures. Row (a) shows the control (before incubation). Row (b) shows incubation after 24 hours. Row (c) shows incubation after 48 hours. Row (d) shows incubation 72 hours. Row (e) shows incubation after 96 hours. Row (f) shows incubation 120 hours. Row (g) shows incubation after 144 hours.

A urinary catheter is a hollow polymeric tube with a perforated tip designed to drain the bladder of urine or allow the instillation of fluids into the bladder. More than 12% of hospital patients are catheterised^1–3 and studies have shown that urinary tract infections account for 23% of all hospital-acquired infections. Studies also show that 44% of hospitalised patients with indwelling catheters have developed significant bacteriuria within 72 hours of catheterisation.¹ Thus, patients often may experience a UTI infection after approximately four weeks, which can extend a hospital stay by three days. Patients with a UTI are also three times more likely to die; the fatality rate from urinary tract related bacteraemia is around 13%.⁵

The problem stems from an infection by urease-producing bacteria such as Proteus mirabilis. These bacteria tend to adhere and colonise catheter surfaces producing a biofilm or coating. This biofilm secretes urease, which releases ammonia and increases the microenvironmental pH around the luminal surface of the catheter.⁷ An elevated pH induces the precipitation of magnesium and calcium phosphate crystals from urine to form struvite, which is an abrasive material capable of damaging urinary tract tissue and also blocking the urinary catheter leading to infection. In clinical practice, this process manifests itself and is often described as encrustation.

Importance of high quality manufactured catheters
A particular cause for concern is the texture and shape of the apertures that are formed within the catheter wall. These apertures are required to allow drainage of urinary fluids and, therefore, they must be perfectly smooth and free from burrs. Most apertures are created by mechanical cutting or piercing/puncturing of the catheter body. These methods have limitations in that they cannot always reliably produce smooth apertures or guarantee the removal of any debris from the punctured or perforated catheter body.⁹

Figure 2: Each row shows images of the ultrasonically cut apertures. Row (h) shows the control (before incubation). Row (i) shows incubation after 24 hours. Row (j) shows incubation after 48 hours. Row (k) shows incubation 72 hours. Row (l) shows incubation after 96 hours. Row (m) shows incubation after 120 hours. Row (n) shows incubation after 144 hours.

Studies by the School of Biosciences at Cardiff University¹⁰ using an artificial bladder model found that the process of encrustation is started by initial cell adhesion of P. mirabilis to irregular surfaces surrounding the catheter eye or drainage holes. Microcolonies form in the depressions of the cut surfaces, allowing the formation of biofilm from which the urease enzymes are released causing the precipitation of the struvite material. Different polymeric materials have lower affinities for cell adhesions; silicone, for example, has a lower susceptibility to encrustation than latex. The major initiation factor was deemed to be the quality of the aperture edge and surfaces. Using scanning electron microsopy, the workers¹⁰ found that engineering techniques used in catheter manufacturing processes produce particularly rough irregular surfaces on the rims (edges) of the drainage holes (eyes). “Catheters available today with their rough, engineered, irregular surfaces around the eye holes and narrow central channels are readily colonised and blocked by crystalline bacterial biofilm,” they wrote. “The development of catheters with larger internal diameters and smoother surfaces, especially around the eye holes, would substantially reduce the problems with current devices.”

Recently, the use of ultrasonic processing technology to cut apertures within catheter bodies has been described with the claim that it can produce smoother surfaces.^11,12

The in vitro performance of ultrasonically cut apertures compared with mechanically cut apertures is described below.
Methodology: Urinary catheters with internal lumens measuring 2.2 mm diam were cut into 50-mm lengths so that apertures could be inserted by means of ultrasonic processing or mechanical cutting.

Mechanical aperture cutting: The mechanical apertures were made using a sharp titanium cutting sonotrode and an aluminium jig to manually hold the catheter tubing and and punch a hole in it.

Ultrasonic aperture cutting: The ultrasonic apertures were manufactured into the body of the catheter using special purpose machines as previously outlined in a paper.¹² The catheters and equipment were provided by Rainbow Medical Engineering Ltd (Letchworth, UK).

Preparation of artificial urine: The method for preparing artificial urine was obtained from Minuth et al.¹³ with a few modifications to suit the purpose of the experiment flasks. The key modification was that the artificial urine was not inoculated with P. mirabilis, as had been done in previous studies.

Encrustation studies
A total of 84 50-mm-long catheters were used. Of these catheter pieces, 42 had an ultrasonically cut aperture created by the method described above and the remaining 42 had a mechanically punched aperture, also as described above. One ultrasonically cut catheter piece and one mechanically cut catheter piece were placed in the same labeled 100-ml Erlenmeyer conical flasks containing artificial urine. The flasks were covered with aluminium foil and placed in an oven heated to 600C. The conditions were set at 600C as a stress acceleration test. These experiments were conducted in triplicate.

Microscopic examination
Samples were removed at 24-hour intervals during the next seven days. The catheters were removed from the artificial urine and left to dry, at room temperature, on weighing boats. A USB digital microscope camera (Veho VMS-004) was used to analyse the eye-holes of the catheter before and after incubation in the oven; images were taken of each sample and crystal growth was measured on each aperture.

Results
Figure 1 shows catheter parts with apertures that were created mechanically at the beginning of the experiment and after various stages of incubation in urine. Figure 2 shows the counterpart catheter sections with ultrasonically produced apertures. In reviewing these images, it is important to note that both catheter types were placed in the same flask of artificial urine to serve as an internal control. The mechanically cut apertures show very visible signs of crystal or struvite debris within 48 hours of incubation; there are comparatively few signs of crystal growth in the catheters with ultrasonically created apertures.

What is perhaps surprising is that these experiments were conducted without the presence of bacteria (typically P. mirabilis); thus, struvite formation was formed in the absence of bacterial biofilm growth. Struvite formation in the absence of bacteria leads to the conclusion that surface roughness or texture also plays a physical role in the precipitation of struvite, which, in vivo, is augmented by the presence of bacteria. It is clear, therefore, that roughened edges provide loci for the crystallisation of inorganic solutes as well as anchorage sites for bacterial biofilm formation.

Better quality catheter apertures
In summary, UTIs are associated with the use of urinary catheters, which is, in turn, related to the way these catheters are manufactured. It is evident that the quality of the apertures with respect to surface finish plays a key role in the physical precipitation of struvite from urine and to the ultimate encrustation of the catheter. The need for better quality apertures and manufacturing processes may help reduce the number of UTIs seen in clinical practice.

It is perhaps worth quoting Stickler and co-workers,10 as follows: “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.”

Luigi G Martini,* FRPharmS, MBA
is Chair in Pharmaceutical Innovation and
Mohammed Taki
is Research Fellow and
Christina Ansu-Damoah
is a Research Student at King’s College London, 150 Stamford Street, SE1 9HN, UK
tel. +44 20 7848 3975
e-mail: luigi.martini@kcl.ac.uk

A.L. Profit
is Director, Rainbow Medical Engineering Ltd, Shaftesbury Industrial Centre, Icknield Way, Letchworth Garden City, SG6 1RRUK
www.rainbow-medical.eu

* to whom all correspondence should be addressed

Disclosure: Professor Martini is also a Director of Rainbow Medical Engineering Ltd.

References
1. R. Crow et al., “Study of Patients with Indwelling Urethral Catheters and Related Nursing Practice,” Nursing Practice Research Unit, University of Surrey, Guildford, UK (1986).
2. B. Roe, “Catheters in the Community,” Nursing Times, 84, 36, 43–44 (1989).
3. A.M. Emmerson et al., “The Second National Prevalence Survey of Infection In Hospitals — Overview of the Results,” Journal of Hospital Infection, 32, 175–190 (1996).
4. Report from the Medical Officer of Health, “Winning Ways—Working Together To Reduce Healthcare Associated Infection in England,” Department of Health (December 2003).
5 S. Saint and B.A. Lipsky, “Preventing Catheter-Related Bacteriuria. Should We? Can We? How?” Archives of Internal Medicine, 159, 800–808 (1999).
6. K. Getliffe , “Freeing the System,” Nursing Standard, 3, 8, 16–18 (1993).
7. D. Stickler et al., “Studies on the formation of crystalline bacterial biofilms on urethral catheters,” Eur. J. Clin. Microbiol. Infect. Dis. 17: 649-652 (1998).
8. N.S. Morris, D.J. Stickler and C Winters, “Which indwelling urethral catheters resist encrustation by Proteus Mirabilis biofilms,” British Journal of Urology, 80:58-61 (1997).
9. L Martini and A.L. Profit, “Manufacturing high quality catheters,” Medical Device Technology, 20, 1; available at www.emdt.co.uk/article/manufacturing-high-quality-urinary-catheters.
10. D. Stickler et al., “Why are Foley catheters so vulnerable to encrustation and blockage by crystalline bacterial biofilm?” Urol Res, 31:306-311 (2003).
11. A.L. Profit and L. Martini, “Using ultrasonic technology to manufacture products,” Medical Device Technology, 17: 30-31 (2008); available at www.emdt.co.uk/article/using-ultrasonic-technology-manufacture-products.
12. Martini L.G. “Manufacturing high quality urinary catheters,” European Medical Device Technology, 20, 1; Available at www.emdt.co.uk/article/manufacturing-high-quality-urinary-catheters.
13. Minuth J.N., Musher D.M., Thorsteinsson B.S., “Inhibition of the Antibacterial Activity of Gentamicin by Urine,” J Infect Dis., 133: 14-21 (1976).