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doi: 10.1111/joim.12220

Clinical complications of urinary catheters caused by crystalline biofilms: something needs to be done D. J. Stickler From the Cardiff School of Biosciences, Cardiff University, Cardiff, UK

Abstract. Stickler DJ (Cardiff University, Cardiff, UK). Clinical complications of urinary catheters caused by crystalline biofilms: something needs to be done. (Review). J Intern Med 2014; 276: 120–129. 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

Introduction This review is a summary of my past experience of working with the bacterial biofilms that block urinary catheters. It is largely based on a previous paper published in the journal Spinal Cord [1]. That paper was intended to deal with the issue in relation to a specific group of patients. In this article I hope to make it clear that the conclusions about how to deal with the problem also apply to the wide range of patients undergoing long-term bladder catheterisation. When Dr Frederick Foley introduced his indwelling bladder catheter into urological practice in the 1930s, he had no idea that he had produced a device which created ideal conditions for the growth of bacterial biofilms. He also had no way of knowing that the biofilms forming on these catheters would create major complications in the care of many millions of disabled and elderly patients. Since its introduction, the Foley catheter has become the most frequently

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ª 2014 The Association for the Publication of the Journal of Internal Medicine

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 nitrofurazonecoated 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. Keywords: bacterial biofilms, Foley catheters, Proteus mirabilis, urinary tract infections.

deployed implantable medical device (Table 1), being exploited for the management of bladder dysfunction in many different groups of patients [2]. Unfortunately, the presence of the catheter in the bladder induces a vulnerability to infection and can result in serious pathologies which are often difficult to treat [3]. It has become the most common cause of infection in hospitals and other healthcare facilities [4]. The fundamental reason why catheterized patients are so vulnerable to infection is that the catheter undermines the defence systems that protect the normal bladder against infection. The regular mechanical filling and emptying of the normal bladder helps to ensure that any bacteria managing to contaminate the urethra or bladder are washed out from the urinary tract. With the Foley catheter in place, on continuous drainage into a urine collection bag, the bladder does not fill and the retention balloon ensures that a sump of residual

D. J. Stickler

Review: Clinical complications of urinary catheters

Table 1 Magnitude of the problem of device-associated infections Estimated no.

Rates of

implanted/year

infection

Device

in the USA

(%)

Bladder catheters

>30 000 000

10–30

Central venous catheters

5 000 000

3–8

Fracture fixation devices

2 000 000

5–10

Dental implants

1 000 000

5–10

Joint prostheses

600 000

1–3

Vascular grafts

450 000

1–5

Cardiac pacemakers

300 000

1–7

Breast implants

130 000

1–2

Mechanical heart valves

85 000

1–3

Data from [2].

urine is maintained below the level of the drainage eye-holes at the catheter tip. As urine then trickles through the catheter rather than flushing the urethra, the migration of bacteria from the contaminated skin insertion site through the urethra is not impeded. In the bladder, the bacterial cells invade the sump of urine which is being replenished from the kidneys. In this continuous culture system, rapid bacterial multiplication results in the development of enormous bacterial populations, generally of around 108 cells per mL of urine [5]. The longer the catheter has been in situ, the more likely it is that bacteriuria will occur. Once a catheter has been in place for about 4 weeks, the urine will become highly contaminated in all patients [6]. Initially, single species colonize the urine but, with time, more complex mixed communities composed of four or five species commonly develop in the urine [7, 8]. Antibiotics are not generally given to patients under these conditions, so contaminated urine can be flowing through a catheter throughout its scheduled life span, which can be up to 12 weeks. Bacteria stick to the catheter surface and, bathed in a trickle of warm urine, they flourish and biofilms develop. In patients undergoing short-term catheterization (up to 7 days), 10–20% will develop bacteriuria. Biofilms will form on the catheter but are sparse and patchy in nature and, as the catheter only remains in place for a short period, are of little concern [9]. In catheters being used for the longterm management of patients disabled by strokes, spinal injury or neuropathies such as multiple

sclerosis or motor neurone disease and those suffering from urinary incontinence or retention however, the biofilms become extensive and can have a profound effect on health and well-being [10]. The most troublesome are the crystalline biofilms that encrust and obstruct the catheter lumen. These can develop rapidly and block the flow of urine. Consequently urine either leaks around the outside of the catheter and the patient becomes incontinent or alternatively urine is retained causing painful bladder distension. If the blockage is not noticed and the catheter changed, reflux of urine to the kidneys occurs and serious complications such as pyelonephritis and septicaemia can result [11]. All available catheter types are vulnerable to encrustation and currently, apart from changing the catheter, no effective methods are available for its prevention or control [12, 13]. Up to 50% of patients receiving long-term care will experience catheter encrustation and blockage [14]. In many cases, the replacement catheters block repeatedly, and the patients are classified as ‘blockers’ [15]. Kohler-Ockmore and Feneley [16] followed 457 long-term catheterized patients in community care in the Bristol area of the UK. Most of the patients were disabled by chronic illness, 26% had experienced a cerebrovascular accident, 12% had senile dementia, 11% multiple sclerosis and others had paraplegia, Parkinson’s disease or prostatism. Over a six month period 506 emergency referrals were recorded, mostly to deal with catheter blockage. The problem thus puts the health of many patients at risk and makes substantial demands on the resources of a health service. The structure and formation of crystalline biofilms The encrustations on catheters are usually composed of struvite and apatite. Struvite (magnesium ammonium phosphate) forms large, often coffinshaped crystals and apatite (a hydroxylated form of calcium phosphate in which some of the phosphate ions are replaced by carbonate) appears as microcrystalline aggregations [17]. Scanning electron microscopy has revealed that large numbers of bacilli are associated with the crystalline formations (Fig. 1) [18]. Mixed populations of bacteria are commonly present and invariably contain species capable of producing the enzyme urease [19].

ª 2014 The Association for the Publication of the Journal of Internal Medicine Journal of Internal Medicine, 2014, 276; 120–129

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D. J. Stickler

Review: Clinical complications of urinary catheters

(a)

(b)

(c)

(d)

Fig. 1 Scanning electron micrographs of crystalline biofilms encrusting catheters. (a) shows a cross-section of an allsilicone catheter removed from a patient after 8 weeks; (b) shows a longitudinal section of a blocked silver-/hydrogel-coated latex catheter removed from a patient after 11 days (adapted from [40], with permission). In both these cases extensive crystalline material can be seen occluding the catheter lumen. The presence of crystals and bacilli in the material encrusting the catheters is shown in (c) (adapted from [25] and (d). (a and d) from [66], with permission).

Urease is the driving force of the crystallization process. It hydrolyses urea in the residual bladder urine to produce two molecules of ammonia to every molecule of carbon dioxide causing a rise in pH. As the urine becomes alkaline, crystallization of the magnesium and calcium phosphates is induced. In the meantime, the bacteria colonize the catheter surfaces forming bacterial biofilm. Aggregation of the crystalline material occurs in the urine, on the catheter and in the developing catheter bacterial biofilm [20]. This process continues until the accumulating crystalline deposits block the flow of urine through the catheter. There can be serious consequences for patients, particularly for those in community care where professional help is not immediately available. Several species that colonize the urine of catheterised patients produce urease [5, 21]. These include Pseudomonas aeruginosa, Klebsiella pneumoniae, Morganella morganii, Proteus species, some Providencia species, Staphylococcus aureus and coagulase-negative staphylococci. Of these Proteus mirabilis is most commonly associated with catheter encrustation and blockage [19, 21, 22]. The urease of P. mirabilis is a particularly active 122

ª 2014 The Association for the Publication of the Journal of Internal Medicine Journal of Internal Medicine, 2014, 276; 120–129

enzyme, being able to hydrolyse urea several times faster than those produced by the other species [23]. The results of experimental studies in laboratory models of the catheterized bladder demonstrated (Table 2) that the only species capable of raising the urinary pH sufficiently to cause extensive encrustation were P. mirabilis, P. vulgaris and Providencia rettgeri [24, 25]. The latter two organisms are only found in about 8% of catheter biofilms (Table 3) [26]. During a prospective study of the urinary flora of patients undergoing longterm catheterization, it was observed that the acquisition of P. mirabilis induced a rapid rise in the urinary pH and resulted in frequent and recurrent catheter blockages [27]. There is thus strong epidemiological and experimental evidence that P. mirabilis is mainly responsible for the formation of crystalline biofilms on catheters. The role of Proteus mirabilis Proteus mirabilis is well suited to life in the catheterized urinary tract [28]. It has at least four different adhesins that mediate its attachment to surfaces. An exopolysaccharide capsule protects it against the host’s defences and helps it to consol-

D. J. Stickler

Table 2 Results from experiments in bladder models in a range of species isolated from catheters

Review: Clinical complications of urinary catheters

Organism

Ureasea activity

pH of urine at

Time taken to

blockage or at 96 h

block catheters (h)

Proteus mirabilis

2.34 (0.21)

8.34 (0.19)

19.8 (2.9)

Proteus vulgaris

2.13 (0.19)

8.42 (0.21)

36.4 (3.9)

Providencia rettgeri

1.85 (0.22)

8.36 (0.19)

32.2 (6.2)

Morganella morganii

1.34 (0.09)

7.39 (0.08)



Staphylococcus aureus

0.28 (0.05)

6.89 (0.06)



Providencia stuartii

0.10 (0.02)

6.44 (0.06)



Pseudomonas aeruginosa

0.06 (0.01)

6.32 (0.05)



Klebsiella pneumonia

0.07 (0.02)

6.31 (0.05)



Escherichia coli

0.06 (0.02)

6.15 (0.02)



Serratia marcescens

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 catheter...
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