Literature review of silver-coated urinary catheters - draft

Joanna Ford, Gavin Hughes and Pete Phillips, SMTL

January 2014

 

Introduction


The aim of this report is to review published information on the subject of silver-coated urinary catheters and to establish whether manufacturer's claims about the benefits of silver coatings are supported by current evidence.

The antibacterial properties of silver have long been known (Hashmi et al., 2003). Silver has been incorporated into an increasing number of medical devices including dressings, central venous catheters and urinary Foley catheters. This paper reviews the studies that have been carried out to investigate the efficacy of silver urinary catheters in reducing urinary tract infections (UTI, also known as 'catheter associated UTI or 'CAUTI').

Two medical device manufacturers now have Foley catheters with silver-containing coatings on the market in the UK. The Bardex IC catheter has a coating containing a silver-alloy layer (i.e. silver combined with other metals, in this case gold and palladium) and a hydrogel layer (manufactured by Bard). This has been available for a number of years in the UK. Tyco Healthcare (now Covidian) have launched the Dover Silver Foley catheter with a silver-based hydrogel coating (i.e. hydrogel containing silver). Both catheters are coated internally and externally.

Urinary tract infections


Most UTIs are experienced by patients with indwelling catheters (Warren 1987), and it has been suggested that UTIs account for 40% of all nosocomial infections in hospitals each year (Rupp et al. 2004). When UTI becomes a problem, it can lead to increased ill-health and prolonged stays in hospital.

Infections tend to originate from one species of bacteria (common examples include Stapylococcus epidermidis, Enterococcus faecalis and Escherichia coli) and as the duration of catheterisation lengthens, more bacterial species are usually detected (these tend to be gram negative bacteria such as Proteus mirabilis and Pseudomonas aeruginosa) (Stickler and Sabbuna 2007).

It has been estimated that up to 4% of patients with UTIs will develop subsequent blood stream infections (Tambyah and Maki 2000, Nazarko 2008), which accounts for approximately 8% of all nosocomial blood stream infections (PHLS, 2003).  It has also been associated with higher rates of mortality in some cases (Platt 1982).

A distinction should be made between symptomatic and asymptomatic UTI. In a case of symptomatic UTI, the patient has clinical manifestations of the infection whereas asymptomatic does not. Asymptomatic UTI (also known as a bacteriuria) is only diagnosed when a urine sample is found to contain bacteria above a defined level. The level of bacteria that defines an asymptomatic UTI can vary. 

The progression of UTI

At some point following catheterisation, bacteria inevitably attach to the catheter surface (Cormio et al., 2001). Images of urinary catheters taken at high magnification have revealed that catheter surfaces are very uneven and covered with microscopic imperfections (Stickler et al., 2003). Bacteria often attach to these areas on the catheter, and can be found intraluminally (within the drainage system) and/or extraluminally (between the surface of the urinary tract and the catheter surface) (Garcia 1999,Tamyah 2004). Bacteria express adhesion proteins on their surface which enable attachment to take place (Hunter et al, 2001). Once this has occurred, bacteria rapidly multiply and colonise the surface of the device, producing a thick matrix known as a biofilm (Kumon et al., 2001). Once biofilm formation has taken place, bacteria within it are resilient to anti-microbial agents (Kumon et al., 2001, Cormio et al., 2001, Burton 2006). The colonised catheter is in intimate connection with the sterile bladder, and infection of the urine and the bladder itself can result (Trautner and Darouiche 2004). Bacteria within biofilms are often protected (Jacobsen et al., 2008) from the action of antibiotics. Unless the colonised catheter is removed, the biofilm has the potential to re-seed the bladder following medication (Trautner and Darouiche 2004).

The biofilm on the catheter surface may not be the only source of UTI-inducing bacteria. One study used a molecular technique called pulsed-field gel electrophoresis on bacterial isolates from the urine samples of catheterised patients (Sabbuba et al., 2003). They identified one patient with a persistent infection of the same strain of P mirabillis over the 121 days that it was sampled. This was despite the fact that the patient had under gone 8 catheter changes, a course of antibiotics and 20 days of non-catheterisation during this period. This data suggests that this patient had a source of this strain of bacteria within their body. One laboratory study used a mouse model with acute UTI and inoculated it with E coli to investigate its impact on bladder lining cells (Anderson et al, 2003). It was already known that bacteria can invade cells that line the bladder but this study was the first to identify and describe "biofilm-like pods" within bladder epithelia containing many bacteria and matrix in an organised arrangement. This suggests that cells lining the bladder could be a 'persistent reservoir' of bacteria (Anderson et al, 2003). This may explain why in some cases, changing catheters and administering antibiotics does not eliminate UTI.

Another complication of catheterisation is triggered by the rapid increase in pH caused by the urease produced by the bacteria. As a result of this increase in pH, crystals of magnesium and calcium phosphate form in the urine and complexes of crystal and bacteria adhere to the catheter and block the lumen in a process known as encrustation (Morris et al., 1997, Stickler et al., 2003). As a result of the manufacturing process, different types of Foley catheters (i.e. catheters made of different materials with various coatings) possess different size lumens (Kassler ad Barnett 2008) which may affect urine flow and rates of encrustation.

Duration of use

Table 1

The following table lists the recommended maximum length of time that manufacturers recommend their urinary catheters are to be used (information gathered from the individual companies who responded to our queries).

Name of product (manufacturer)

Catheter material

Surface coating

Recommended maximum

duration of use (in days)

Bardex IC (Bard)

latex

hydrogel and silver alloy

28

Sympacath (Teleflex Medical) and Biocath (Bard)

latex

hydrogel

90

Aquaflate (Teleflex Medical) and Bardia PTFE (Bard)

latex

teflon

28

Curity (Tyco)

latex

silicone

30

Ultramer (Tyco) and Lubrisil (Bard)

silicone

hydrogel

90

Dover (Tyco)

silicone

hydrogel (containing silver)

90

Folysil (Coloplast), Silflate (Teleflex Medical), Bardia all silicone (Bard) and Argyle (Tyco)

All silicone

None

90


The perceived benefits of silver in infection prevention


The ability of silver to kill bacteria has long been established in the literature. It has been used as an antibacterial agent in humans for centuries, particularly in the area of wound healing (Landsdown 2006, Landsdown and Williams 2007). This has included the use of silver sulphadiazine creams and more recently, silver-releasing dressings. The antibacterial activity of silver occurs when ions form in solution (Landsdown 2006), adding bacteria to a solution of silver ions leads to bacterial death (Scierholz et al., 2002). Silver ions kill bacteria by damaging their cell membranes (Percival et a., 2005). In the catheter field, some studies have shown that silver alloy is more effective in terms of its bactericidal properties than silver oxide which was used in some of the earlier coatings (Hashmi et al., 2003, Madigan and Felber 2003, Rily et al., 1995, Saint et al., 1998). Silver alloy is silver combined with other metals whereas silver oxide is a chemical compound of silver and oxygen. The Bardex IC catheter has a silver-alloy coating (a gold and palladium coating containing metallic silver, covered by a layer of hydrogel), whereas the Dover silver catheter is coated with a hydrogel containing silver ions. Both will be described as silver-coated catheters for the purpose of this report.

In December 2004, the Bardex IC catheter was considered at a Rapid review panel (RRP) which reviews products that may be of value to the NHS in terms of improving infection control in hospitals and provides recommendations to the Department of Health (DH 2005). It was the only product to receive a level one recommendation which indicated that it should be made "available to NHS Trusts and PCTs as a key component of their infection control protocols" (Jenkinson 2006). The review panel, however, based their decision on data provided by the company (such as peer reviewed publications) about the clinical efficacy of the product (personal communication with member of RRP). As far as the authors have been able to ascertain, no independent literature review was performed.

2 Literature review


A systematic review of the literature was performed and relevant papers were identified by searching the PubMed database for the following key words:

  • Catheter with infection/biofilm/urinary/urethral/silver/Foley/economic/cost
  • UTI or CAUTI with silver
  • Silver with hydrogel
  • Bard or Bardex
  • Dover and silver
  • bacteriuria
  • EPIC

Citations used in each retrieved article were examined and any relevant papers included in the review. In addition, Bard provided a range of data (including full publications, meeting abstracts and poster presentations) and some abstracts were provided by Tyco.

The studies are summarised in the appendices. Clinical studies investigating the effects of silver-coated catheters on UTI rates have been categorised as either interventional or randomised studies depending on their design.


Interventional studies

The interventional studies (also known as pre-post studies) involve introducing a silver-coated catheter into a clinical setting (either a ward, whole hospital or group of hospitals) where clinicians switch from using the "standard" catheter they usually use on patients to the experimental one for a fixed period of time. Changes in UTI rates are then calculated by comparing new UTI rates with rates that were recorded during the period prior to the introduction of the new catheter. None of the interventional studies described were funded by Bard Ltd or Tyco (communication with representatives from both companies).

The study periods for the reviewed papers ranged from approximately 3 months to 3 years (see table 1 of appendices for full list of published interventional studies reviewed). In most cases, UTI rates were shown to decrease following the introduction of the Bard catheter. Tyco provided 2 abstracts of meeting presentations describing interventional studies showing a reduction in UTI following the introduction of the Dover Silver catheter (Bystrom 2005, McArdle 2005). Reduction in UTI rates ranged from 30% (Collins et al., 1999) to over 70% (Bystrom 2005, McArdle 2005). Most studies calculate infection rates as the number of infections per 1000 catheter days (or patient days). A few exceptions calculated rates per 100 patients admitted (Ramirez et al, 1998, Lettau and Blackhurst 1998, Hernandez  1999). Large percentage differences however, did not always represent large numbers of infections, for example, in one study (Barron et al., 1998) a 69% decrease represented only 7 infections (a reduction from 10 to 3 infections per 1000 catheter days after the silver catheter was introduced). In another, a 73.8 % reduction in UTI rate equated to approximately 1 less case of UTI per 1000 patient days (Bystom 2005). One US study introduced a '100% silicone, ionic silver catheter' (model name not provided) into a rehabilitation hospital and detected no UTIs in the 6 months after they were introduced (described as a 100% reduction). Five studies reported a non-statistically significant reduction in UTI rate and one study reported no decrease at all (Accuntius and Corron 1999). In fact, in three out of the four wards studied by Accuntius and Corron, an increase in UTI was detected.

Five of the studies reviewed made it clear that a case of UTI included the identification of symptoms as well as positive urine cultures. A couple of papers were specific in stating that they only used urine cultures to determine UTI rates but the majority of studies did not specify whether a case of UTI was determined by urine culture results alone or by clinical symptoms.

The disadvantage of 'pre-post' studies such as these are that many conditions are likely to have changed between the two groups which may affect results. For example, historical data of recorded infections before the new catheter was introduced may not be as thorough as the data collected during the post interventional period, nursing staff may have changed and procedures may be carried out differently. It is not possible to eliminate the impact of such variables on the results because the two catheters were not tested under exactly the same conditions. Problems with interventional studies are well understood by medical statisticians, as they have a tendency to yield more optimistic results than randomised trials, flattering the experimental group in comparison with the historical control group (Sacks et al., 1982). The bias that is introduced with pre-post studies makes this approach "seriously flawed" according to Altman and Bland in the BMJ (1999).

Another disadvantage of these study designs is that the process of being observed during a study has been shown to improve performance (such as closer adherence to recommended practice), a phenomenon known as the Hawthorne effect. If the experimental arm of the study was performed with the fore-warning of ward staff, but the historical data was collected after the fact, then the study results may have been influenced by this phenomenon.


Randomised studies

The randomised experiment overcomes these issues to some extent by randomly allocating patients into an experimental group (in this case, a silver-coated catheter group) or a control group (a catheter that does not contain silver) and the UTI rates of the two groups are directly compared in parallel. This is to ensure that other factors are balanced out over the two treatments. Usually the percentage of patients in each group who develop UTI (or the rate of UTI per 1000 patient/catheter days) are compared with each other and a statistical test is employed to determine whether the differences observed are statistically significant. See table 2 of the appendices for a full list of published randomised studies reviewed.

In some of the cases, total randomisation (where each patient has equal chance of being in either group) was not carried out. For example, in one study, all the subjects on the same ward were given the same catheter and wards were compared (Karchmer et al., 2000), whilst in another, the catheter available for use was alternated each week so it depended when a patient required a catheter as to what product they would receive (Verleyen et al., 1999).

In the randomised studies reviewed, two of the studies were funded by Bard (Liedberg and Lundeberg, no date, & Karchmer et al., 2000) but the rest were independent. In the studies reviewed (full papers and abstracts included), most reported significantly greater UTI rate in patients with the control catheter compared with the silver-coated catheter (see table in appendices). In these studies, control catheters were described as non-coated (Verleyen et al., 1999, Lieberg et al., 1990), standard (Lundeberg 1986, Thomas et al., no date), uncoated latex (Karchmer et al., 2000, Verleyen et al., 1999), teflon-coated (Liedberg and Lundeberg 1990), hydrogel-coated (Liedberg and Lundeberg, no date) and in one case, no detail was provided (Garcia et al., 1999). However, a few studies reported non-significant differences between the two groups. Silver-coated catheters were compared to 100% silicone (Thibon et al., 2000, Verleyen et al., 1999, Naada et al., 1996), hydrogel-coated (Liedberg et al., 1990) or ptfe-coated latex (Pickard et al., 2012). Only three studies clearly indicated that a UTI was identified by both urine cultures and symptoms (Karchmer et al., 2000, Thomas et al., no date and Pickard et al., 2012). All the other randomised studies either used urine cultures alone, or the criteria they used to classify UTIs was unclear.

Cost Analysis studies

A number of clinical studies (some published as papers, others as abstracts) looked at the cost savings that could be made if the silver-coated catheter was adopted, based on the UTI reduction rates seen in their studies (see table below). In all the cases reviewed, reports stated that cost savings were made, mainly due to the reduced costs of treatment and reduced hospital days seen with less UTIs.

Table 2

The table below summarises the results of four published studies that calculated the costs saved when silver-coated catheters were used.

  Study (design) 

UTI definition    

   UTI Result 

Estimated cost per UTI    

   Total estimated cost savings     

Lai and Fontecchio 2002 (interventional)

Systematic urine samples (taken at regular, defined time intervals) no further details 5% reduction in UTI when silver-coated catheter used $1214 $12,000-142,000
(costs for 1 month)
Karchmer et al., 2000 (randomised)  Symptomatic and asymptomatic UTI Significant difference between groups $839-4693 $14,000-573,000 (costs for 1 year)
 Rupp et al., 2004
(interventional)
Symptomatic and asymptomatic UTI  57% reduction in UTI when silver-coated catheter used  $700-5682 $13,000-535,000 (in 1st year of study)
$5800-480,000 (2nd year of study)
 Gentry and Cope 2005 (interventional)

Symptomatic 33.5% reduction in UTI when silver-coated catheter used £1327  Â£2654 during the 1 month study period (the authors did not subtract the additional cost of silver catheters from this value)

 

In addition to the above data, the cost of one blood stream infection derived from a UTI patient has been estimated as $2041 (Bystrom 2005).

There are a number of issues regarding cost calculations of this sort. Cost calculations are based on the reduction of UTI rates that are recorded when the silver-coated catheter is used. If a study is calculating UTI rates from systematic sampling of urine from all patients (this practice is carried out in the majority of studies) the results will be misleading, as systematic urine sampling is not routine practice in clinical settings and the only UTIs that are usually recognised and treated have clinical symptoms associated with them (communication with continence nurses). This means that most UTIs identified in the silver-coated catheter studies would not have been identified or treated during routine clinical practice. One study reported that more than 90% of the UTI cases they identified were asymptomatic, identified by urine sampling only (Tambyah and Maki 2000). If cost/benefit analysis includes the cost of treating an asymptomatic UTI that would not normally be identified outside of study conditions, then the cost calculations are not realistic .

One author devised an economic model and estimated that using silver-coated catheters would reduce symptomatic UTI rates by 47% which would lead to a saving of approximately $4 per patient catheterised (Saint et al., 2000). Calculations included costs of the devices and tests. The same paper indicated that if less than 5% of UTIs were symptomatic, using silver coated catheters would not provide any cost savings . It is clear that until calculations are based on the number of UTIs that would actually be identified and treated in a clinical situation, cost-benefit analysis exercises based on asymptomatic UTI are likely to significantly over-estimate any potential cost savings.

The methods used in all the papers described above have quality issues which effect the validity of the cost estimates they make. For example, all but one of the studies were pre/post interventional studies comparing historical data with new data to calculate the reduction in UTI rates, and the disadvantages of this design have already been discussed. Only one paper described its study design as "randomised" (Karchmer et al. 2000), however this was misleading as all patients on the same ward were given the same type of catheter and wards were then compared. This is not true randomisation and variability between wards and ward practice cannot be eliminated. Basing cost calculations on inadequate  studies means that the predicted protective effects are likely to be over-estimated, and the predicted cost-savings unrealistic.

Other systematic reviews

A number of critical reviews have been published in this area and their findings are summarised below:

Saint et al, 1998

Saint et al. carried out a meta-analysis of eight clinical studies that compared the UTI rates when silver-coated catheters were compared to un-coated catheters. All eight papers used asymptomatic bacteriuria as their clinical end point. Four of the papers reviewed used catheters with silver alloy whilst the other four used catheters containing silver oxide. Results indicated that silver alloy was significantly more effective in reducing asymptomatic bacteriuria than silver oxide when used in a catheter coating. However, they did state that their results should be 'treated with caution' because of the variation between study designs and they admitted that studies on the subject were of a variable quality.

Bandolier (an online journal which discusses evidence-based healthcare issues) wrote an article about this meta-analysis paper and emphasised Saint's conclusion that one should be cautious with the results. Reasons for this included the variation in study design, the range of bacteriuria rates between studies (ranging from 10-55%) and the fact that all the silver alloy studies were carried out by the same investigators (Bandolier report 1998).

Niel-Weise et al, 2002

Niel-Weise reviewed seven clinical studies where silver-coated and uncoated urinary catheters were compared. They scored each study for quality, based on a number of criteria including whether they were appropriately randomised, whether the researcher was blinded and the completeness of follow-up. Only one trial received a top score, the others received the lowest score for study quality. Examples of poor quality included the fact that the researcher was only "blinded" in one of the seven studies reviewed, details of drop-outs were not included in some studies and distribution of gender and antibiotic agents used was not equal amongst groups of subjects that were compared. They concluded that there was "insufficient evidence to recommend the use of silver-coated catheters".

Davenport et al, 2005

This review concluded that silver-coated catheters reduce asymptomatic bacteriuria, particularly in patients that were catheterised for less than seven days. However, they reported that there was incomplete data at present to recommend them for long-term use. Currently, silver-coated catheters are only recommended for short-term use.

Trautner et al, 2005

Trautner et al. looked at technologies that aimed to disrupt biofilm formation on catheters (which included catheter coatings). They concluded that the "use of more expensive, silver-coated catheters to prevent UTI is not supported by quality data".

Cochrane reviews, 2004 and 2009

Both reviews investigated the same question, the first included 18 randomised studies and the second reviewed the same papers as the first, and included five additional studies. All reviewed papers used asymptomatic and symptomatic UTI as their clinical endpoint. The first review concluded that "evidence suggests that silver-coated catheters prevent UTI in short-term patients (defined as 'up to and including 14 days'), although trials are of a general poor quality' (Brosnahan et al., 2004).  The most recent review stated 'silver alloy coated catheters might reduce infection in hospitalized adults' and that 'larger, more scientifically rigorous trials are needed' (Schumm and Lam 2009).

Johnson et al, 2006

Johnson systematically reviewed 12 randomised studies of anti-microbial catheters (both silver coated and nitrofurazone coated) with standard catheters (either latex or silicone controls) during short term catheterisation (defined as less than 30 days). They stated that the evidence suggested that anti-microbial catheters prevent short term bacteriuria compared with control catheters. However, the quality of studies was considered to be generally poor. The reasons for this included the number of post-randomised exclusions (up to 27% of participants were excluded in some cases) which may have magnified the anti-microbial effect in some studies. In addition, no studies addressed symptomatic UTI and very few addressed blood stream infections. Johnson felt that the lack of clinically meaningful endpoints (such as symptomatic UTI, morbidity and blood stream infections) flawed the studies they reviewed. They stated that clinical evidence of UTI is uncommon even if the patient has a positive urine culture, and that there is a clear need for better quality studies to address some of these issues.

Centre for evidence-based purchasing, 2006

The Centre for evidence-based purchasing (CEP) was a division of the Purchasing and supply agency in England's NHS (it was decommissioned in 2010 and has now integrated with NICE). The CEP produced a report that reviewed the evidence surrounding the clinical efficacy of the Bardex IC Foley catheter. The front page summary concluded that the product had "significant potential" and that there was a "significant body of evidence ... which indicates that the product might be effective in reducing CAUTI in short term catheterised patients". However, the main body of the report stated that "no firm conclusions could be drawn" as most of the studies reviewed "suffered from significant limitations" such as small population sizes, no suitable controls, poor definition of infection and poor overall study designs.

Other recent reviews

More recent reviews of silver-coated urinary catheters which have looked at RCT studies as well as the information contained in previous systematic reviews reach the same conclusions as the above papers - that although some studies suggest potential benefits, the quality of investigations was often poor and unreliable (Scott 2010, Beattie and Taylor 2011).

Methodological problems with the available literature

Study design

The reviews above conclude in general that, although silver- coated catheters may reduce UTI rates (usually defined as asymptomatic bacteriuria) in many cases, results are mixed and inconclusive (Lawrence an Turner 2005, Leone et al., 2004).  As every study is designed slightly differently this is likely to have influenced the variety of results and conclusions reported. This includes factors such as variation in practice, methods of identifying and defining UTIs, infection control procedures, precautions taken, subject group composition and study methods. If different hospitals were consistently finding a similar reduction rates in symptomatic UTI following the introduction of a silver-catheter, one could place more confidence in the reported results. However, the range of outcomes between studies is substantial.

Other limitations of many of the reviewed studies include:

  • small sample sizes
  • only one gender included in the study population
  • using historical data rather than an appropriate control
  • very few studies randomised individuals into treatment groups

Quality of data

Another issue of concern is that many of the clinical studies have been supplied only as abstracts because they have been presented at meetings and have not been published as full articles to date. In these cases, much of the study detail is excluded and it is unclear if they have been subjected to peer review. Some of the reviews mentioned above discuss the poor quality of many of the studies. In addition, inadequate reporting of information raises questions about study quality (Schulz et al., 1995). The following table summarises the quality of the randomised clinical studies (the six summarised in the table have been published as full articles). Ideally, a good quality study of these devices should include a blinded researcher and clear details about the patient groups included in the analysis (such as patient drop-outs and withdrawals during the study). The table shows that this was only the case in two of the six papers reviewed.

Table 3

Quality of randomised studies

 Paper Was researcher blinded? 

 Were patient drop-outs

and withdrawal discussed?  

Liedberg '90a No No
Liedberg '90b No No
Verleyen '99 No Yes
Karchmer '00 No No
Thibon '00 Yes Yes
Pickard' 12 Yes Yes

 

Post exclusions

When patients are randomised into groups, individuals are often excluded from the analysis at the end of the study (i.e. post-enrolment exclusion). Investigators may have left subjects out of the analysis because they did not receive the catheter that they were meant to, they had a UTI before the study commenced, they received antibiotics or there had been catheter care violations, for example. Of all the randomised clinical studies reviewed in the earlier section, only three described post-randomisation exclusions. Most statisticians agree that analysis should include all subjects regardless of withdrawals because it maintains the balance between the groups and produces a more realistic outcome. It has also been argued that post exclusions may skew results by exaggerating the positive effect of a treatment which can make the results misleading (Johnson et al, 2006), although some would argue that there are occasions when post-randomisation exclusions are appropriate (Fergusson et al., 2002).

Endpoint of studies

A major limitation of the studies reviewed is that they tend to use asymptomatic bacteriuria (i.e. bacteria in urine) as the end point of the trial (Saint et al., 1998). This method has been criticised because asymptomatic UTI is not considered to be clinically significant whereas symptomatic  UTI is of clinical interest (Stickler and Sabbuba 2007). In most clinical practice, urine samples are not taken routinely but only if a patient exhibits clinical symptoms of UTI (communication with Continence Advisors in Wales). In addition, treating asymptomatic bacteriuria is 'not recommended' because of the potential for selecting resistant organisms (Jacobsen et al., 2008). Studies that use urine cultures as their endpoint have been described as "flawed" (Trautner et al., 2005) and the limitation of this method has been identified by a number of reviewers(Trautner et al., 2005, Johnson 2006, Niel-Weise 2002). Even the definition of bacteriuria (i.e. the concentration of bacteria identified in a urine sample) varies between studies (Niel-Weise 2002, Johnson 2006, Tambyah 2004). This can influence UTI rates from one study to another. It has been suggested that even if they are identified, most asymptomatic UTI should not be treated with antibiotics because the risk to the patient is low, it promotes bacterial resistance, does not appear to prevent recurrence of UTI (Trautner and Darouiche 2004) and rarely progresses to symptomatic UTI (Trautner et al., 2005). UTI only tends to be treated with antibiotics if the blood or kidneys have been infected (Stickler and Sabbuba 2007).

Some of the studies stated that they used the National Nosocomial Infections Surveillance System (Centre for Disease Control and Prevention, USA) to define UTIs (CDC, 1981). However, this system includes definitions of both symptomatic and asymptomatic UTI and most studies did not specify whether the results they provided referred to infections that satisfied both criteria (i.e. positive urine culture plus clinical symptoms). Therefore, it is not always possible to differentiate between symptomatic and asymptomatic infections in these studies.

One study investigated the issue of symptomatic versus asymptomatic infection in detail, in order to define the clinical features of catheter-associated UTI and to establish the extent of the problem (Tambyah and Maki 2000). Nearly 1500 newly catheterised patients took part in the study. From the day of catheter insertion, urine cultures were taken from all patients and researchers investigated symptoms on a daily basis. Their results indicated that 15% of the catheterised patients had UTI (defined as >105 cfu per ml) but that only 10% of this 15% (i.e., 1.5% of the total study population) also had clinical symptoms of UTI. Four cases of blood stream infection (thought to have originated from the UTI) were detected in the entire patient population investigated. The authors argue that clinical signs of UTI are fairly rare in catheterised patients and that the use of asymptomatic UTI as their endpoint is less useful than a symptomatic endpoint from a clinical perspective.

Sampling methods

When a sample is taken from a catheter, it is the free-floating bacteria which are sampled and detected, whereas the chronic infection may be due to the biofilm on the catheter (Trautner and Darouiche 2004). The microbiology results can produce misleading information because the bacterial species which are free-floating may be different to those present in the biofilm. Results can also vary depending on whether a sample is taken from a newly inserted catheter, a catheter which has been in situ for some time or a sample taken directly from the bladder (Trautner and Darouiche 2004, Jacobsen et al., 2008). For example, higher concentrations and different species of bacteria have sometimes been sampled from catheters that have been in situ for a long time in comparison to a sample taken from a newly inserted catheter in the same patient (Trautner and Darouiche 2004). In addition there has been research to suggest that bacteria can invade bladder epithelial cells and form biofilm-like pods (as described in previous section)(Anderson et al, 2003). This may mean that some patients continue to sustain a bladder infection no matter what type of catheter is used.

The actual technique of sampling the urine may also produce misleading results. To obtain sufficient urine, samples are often taken by clamping the catheter and allowing it to fill up before the sample is collected. Leaving a column of urine in the catheter for extended periods of time might permit more silver ions to elute into the urine than when the urine flows freely through the catheter as it would usually. This may also occur if samples are taken from the drainage bag (as carried out in Liedberg et al., 1990) where urine may have collected for hours and further leaching of silver ions from the catheter may have occurred. Therefore, it is possible that urine samples collected from the silver catheters might have antibacterial activity, resulting  in loss of viability of any cells present in the sample during the time between collection of the sample and its examination in the laboratory. This could be easily checked with appropriate controls but it does not seem to have been carried out in any of the studies (communication with Dr David Stickler, Cardiff University). The low numbers of bacteria seen in some studies with silver catheters may therefore be purely a function of the sampling method, and not representative of the microbiological flora in the bladder. If this is the case, many of these studies are no more helpful than standard laboratory antimicrobial contact assays, as the effect of silver in close contact with bacteria in the laboratory is well demonstrated.

Expression of results

The way the results are expressed can effect how the outcome is interpreted. In randomised studies, the most common way of expressing results is to compare the percentage of patients in each group that develop UTI during the study period. However there are other ways to express the results. This is illustrated in a study by Karchmer (Karchmer et al., 2000). When differences between the two patient groups were expressed as a percentage of patients developing UTI (1.1% vs 1.36%) there was no statistical difference between the two groups (P = 0.07) but if they were expressed as 'risk of infection per 1000 patient days' (2.66 infections per 1000 patient days versus 3.35 infections per 1000 patient days) the results reached significance (P = 0.04).

Other factors affecting results

Catheter duration

The length of duration for catheterisation can impact on UTI rates, according to one study by Verleyen et al., 1999. In this study, patients that were catheterised for an average of five days lead to a significant reduction in UTI with silver but those who were catheterised for approximately 14 days did not. It is possible that the anti-bacterial action of the silver is less effective in the later stages of the catheter use because most or all of the silver has been released by this stage.

Patient differences

UTI rates can also vary depending on the type of patient, as demonstrated in (Lucente et al., 1997), where patients from medical, surgical and coronary ICUs demonstrated different UTI rates. No explanation for this was provided. However, differences in treatment, immunity, exposure to infection and recovery times between groups of patients may influence the likelihood of different patients developing a catheter-related infection.

Bacterial species present

Silver-coated catheters may also have different success rates with different types of bacteria (Maki et al., 1998), where silver-coated catheters demonstrated substantial protection against organisms that typically accessed the catheter extraluminally but were only marginally effective against others that favoured intraluminal access. No further detail was provided to explain why the silver had different levels of success with different bacterial species but it may be due to the biology of the organism itself and it's susceptibility to silver, or the different environment of the internal and external surface of the catheter.

Catheter care violations

An early study (on a silver-oxide catheter) stated that "catheter care violations" (such as interruption of the catheter-tubing junction or improper clamping of the drainage port) were associated with nearly a three-fold increase in the risk of UTI (Johnson et al., 1990). It is possible that catheter care violations may have been the cause of UTI in some of the studies under review, but because this was either not recorded or reported it is not possible to estimate the likely effect.

Health Technology Assessment - A multi-centre randomised controlled trial

Recently, a major randomised control trial has been conducted and it is dealt with separately here because it was designed specifically to address some of the quality issues identified in many of the previous studies mentioned (Pickard et al., 2012). It involved over 6000 catheterised patients in 24 NHS hospitals throughout the UK who were randomised to silver-alloy hydrogel-coated latex, nitrofurazone-impregnated silicone or PTFE-coated latex (control).  The number of patients involved in this study gave it the power to produce statistically meaningful results.  The study was blind where possible (i.e. nobody involved was told which catheter was being used although some differences in appearance could be noted between different catheters and urine samples were analysed in a blind fashion).  In addition, a major reason for conducting this study was to use clinically meaningful endpoints which have been lacking from many previous trials, including clinical symptoms experienced by patients, as well as bacterial counts in urine samples. Within 6 weeks of initial catheterisation, 12.5% of patients had developed CAUTI when using the silver catheter compared with 12.6% for the control catheter group (non-significant difference). The nitrofurazone catheter performed better with 10.6% of patients developing CAUTI. This study concluded that there was no clinical benefit in using silver-coated catheters and that their use was not considered to be cost effective.  

The use of a non-antimicrobial hydrogel coated catheter for the control may have been a better choice, as in other studies it wasn't clear whether the hydrogel had an antimicrobial effect.   However, the fact that even a 'sub-optimal' control (PTFE coated latex) performed as well as the silver catheter demonstrated that no significant clinical effect was attributed to the silver-catheters compared to their conventional counterparts.   

Silver - is it the essential factor ?

Clinical studies

A factor that may affect UTI rates is the type of "standard" catheter that the silver-coated catheter is being compared with. Apart from the multi-centre trial described above, five published papers were reviewed that described a series of randomised clinical studies where silver-coated catheters were compared with other types of urinary catheter (see table below). In the studies reviewed, a range of urinary catheters were used as "controls" including standard uncoated latex catheters, but also those made of 100 percent silicone, teflonised latex, and hydrogel-coated. When un-coated latex was used as a control, a significant difference in UTI rate was detected between groups. However, in the studies where non-significant differences in UTI rates were seen, a range of control catheters were used including 100% silicone catheters (Verleyen et al., 1999, Thibon et al., 2000), hydrogel-coated latex (Liedberg et al., 1990) or silicone-coated (Karchmer et al., 2000, Nakada et al., 1996, abstract available only). The following table illustrates the findings of these studies:

Table 4

Randomised clinical studies comparing silver-coated catheters to a variety of 'control' catheters

Study"Control" catheter   Description of silver catheter    Outcome expressed as:-    Result  
Thibon et al., 2000

100% silicone hydrogel and silver salt-coated

Percentage of patients that

developed UTI

 Non-significant difference

Verleyen et al., 1999

- study a

100% silicone Bardex IC

Percentage of patients that

developed UTI

 Non-significant difference

Verleyen et al., 1999

study b

latex Bardex IC Delay of UTI onset  Significant difference (P<0.003)

Liedberg et al., 1990

study a

Hydrogel-coated silver alloy and hydrogel-coated

Percentage of patients that

developed UTI

 Non-significant difference

Liedberg et al., 1990

-study b

Standard silver alloy and hydrogel-coated

 Percentage of patients that

developed UTI

 Significant difference (P<0.002)


Karchmer et al., 2000

Latex based, silicone

elastomer coated

Bardex IC

Percentage of patients that

developed UTI

 Non significant difference (P=0.07)
Liedberg and Lundeberg 1990

Teflonised latex silver coated latex

Percentage of patients that

developed UTI

 Significant difference (P<0.01)

Nakada et al., 1996

(abstract only)

silicone-coated Silver Lubricath

Risk of bacteriuria (no further

details)

 Non-significant difference

These findings raise the question of whether the differences in UTI rates observed in some studies are affected by the type of "standard" catheter that the silver-coated catheter is being compared with. Is the silver responsible for reducing infection rates or would another type of catheter (such as 100% silicone or hydrogel-coated) also have the same effect? If a hydrogel-coated catheter was found to be as effective in reducing UTIs as a silver/hydrogel catheter, it may be more cost effective to use the hydrogel-coated catheter to obtain a similar clinical benefit. Good scientific practice would usually specify that the most appropriate control for a silver/hydrogel-coated catheter is a hydrogel-coated catheter, as this eliminates the effect of other potentially significant factors (such as coatings), allowing the effect of the silver to be determined directly (Stickler et al., 2003) . 

Again, this highlights the problem of many of the studies not being adequately controlled, with too many factors differing between studies. In future studies, we would recommend that the base catheter materials should be identical, so that the only difference is the presence or absence of silver.

Laboratory studies

In one laboratory study (Schierholz et al., 1999) polyurethane catheters were dipped in bacterial broth before being incubated in silver nitrate solution. Many of the "free" bacteria were killed in the solution, but the silver had very little effect on the adherent bacteria, which are the bacteria most likely to form a biofilm. In another laboratory study (Cormio et al., 2001), sections of teflon-coated, silver-coated and hydrogel-coated catheters were inoculated in various bacterial solutions with or without previous dipping in antibiotic solution. Following inoculation, catheter sections were washed, sonicated in saline to remove adherent bacteria, and the saline was then plated onto agar and the number of colony forming units counted. If catheters were dipped in antibiotics prior to inoculation, the bacterial adhesion was reduced on all types of catheters, but if antibiotics were not used there was no significant difference seen between the adherence levels of bacteria on the three types of catheter. The authors concluded that presence of antibiotics was the significant factor in reducing bacterial adherence and not the material of the catheter.

A recent study compared the performance of the Bardex IC catheter with a novel anti-microbial coating by innoculating in bacterial broth and comparing bacterial adherence using methods similar to the above studies (Hachem et al., 2009). The study found that catheters with a novel coating of Gentian Violet and chlorohexidine (which authors had named 'Gendine') performed significantly better than the silver-coated catheter or an all-silicone catheter (no significant difference in bacterial adherence was found between the control and the silver catheter) which was confirmed by scanning electron microscopy (Hachem et al., 2009).    

In one in vitro study, sections of a nitrofurazone-containing Foley catheter and a silver hydrogel catheter (Bardex IC Lubricath) were added to agar plates streaked with bacteria in order to establish their anti-microbial activity by 'inhibition zone assay' (Johnson 1999). They also moved the same catheter sample to subsequent inoculated agar plates at different time points to establish the duration of bactericidal activity. The nitrofurazone-containing catheter samples inhibited significantly more bacterial strains than the silver-coated catheter, with measurable activity up to five days, whereas the silver-coated catheter demonstrated a small amount of antimicrobial activity on day one alone. The same author challenged catheters (all silicone control, nitrofurazone-coated and Barc IC silver-coated catheters) with 11 different organisms in innoculation broths in a very recently published study (Johnson et al., 2012). Levels of viable bacteria that adhered to catheters were investigated as well as  levels of 'diffusible inhibition' (i.e. levels of viable bacteria remaining in the broth as an indication of the catheter's anti-microbial activity in the surrounding environment). The nitrofurazone-coated catheter out-performed the silver-coated and control catheters in both tests. 

One of the issues that has been raised about the antibacterial activity of silver ions is that, once they are released, silver ions tend to bind to protein molecules they come into contact with. It is only 'free' silver (that is not bound to protein) that has the potential for antibacterial activity (communication with Dr Alan Lansdown at Imperial College who has published extensively on the use of silver in medical devices). Other laboratory studies have shown that the bactericidal activity decreases in the presence of horse serum (Kampf et al., 1998) and broth containing albumin. It is therefore unclear how much of the silver released from the catheter surface is available to kill bacteria in vivo but it is likely that albumin in contact with indwelling catheters in the body will bind to silver and reduce its anti-microbial activity (Kampf et al., 1998).

This relates to an important methodological issue with studies involving silver-coated medical devices. The importance of neutralising silver activity before an assay is carried out is stressed in a number of papers detailing studies of silver-containing central venous catheters (Schmitt et al., 1996, Kampf et al., 1998, Schierhilz et al., 1999, Bach et al., 1994). Inactivation of residual silver activity immediately after the experiment ensures that the assay does not produce results which are falsely low, making it look as though the silver has killed more bacteria during the experiment that it actually has  (Bach et al., 1994). It is not always clear from papers whether laboratory studies have neutralised silver activity prior to analysis.

Tyco provided an independent technical paper (not funded by Tyco and neither peer reviewed nor published in a journal), from a US company called Bacterin (Cook and Costerton 2006). They incubated the Dover Silver, the Bardex IC and the Dover uncoated silicone Foley catheter with six different bacterial suspensions (each containing a different species of bacteria). Catheters were scraped and the suspension inoculated in sterile broth every 24 hours for up to seven days. In addition, cell attachment and viability on catheter surfaces was investigated by using molecular probes that distinguish between live and dead cells which are then visualised using confocal scanning laser microscopy. Results indicated that bacteria on the Bardex IC catheter had much higher levels of bacterial attachment and viability for three out of the six species of bacteria investigated after 48 hours, whereas the Dover Silver catheter appeared to reduce bacterial adherence and viability of all species up to day seven with one exception (i.e. Proteus mirabilis viable at day five). Proteus mirabilis is one of the most common species of bacteria associated with catheter-related infections. It must also be noted that this study inoculated each catheter with only one species of bacteria but more than one bacterial species is usually present in biofilms.

Morris et al. (1997) used a bladder model to investigate catheter blockage rates following inoculation of artificial urine with Proteus mirabilis. Results showed that all-silicone catheters took longer to block than coated catheters. The Bard hydrogel/silver coated catheters became encrusted more rapidly than any other catheter type investigated during the study. It was thought that catheter bore sizes and eye hole diameters may have played a role in the results as the non-coated catheters had larger bore sizes than the coated models.

Issues surrounding use of Silver

Resistance

Silver is used as a biocidal agent in a range of clinical and non-clinical applications. For example, silver can be found in some cosmetic preservatives, drinking water, sports clothing and dental fillings (Silver 2003, Silver et al., 2006). In the healthcare sector, it has been of particular interest because silver appears to be effective against antibiotic-resistant organisms ((Wright et al., 1998). However, increased use of silver for numerous applications risks the selection for silver-resistant mutants. A common approach to investigate silver resistant organisms is to culture them on agar containing serial dilutions of silver nitrate. Silver resistant strains of bacteria have been identified in the past in both environmental and clinical situations (Slawson et al., 1992, Silver 2003, Ip et al., 2006) and mutants have been selected for in the laboratory (Li et al., 1997). Genes have been identified in silver-resistant bacteria that protect it from death by silver activity (Landsdown and Williams 2007) although genetic evidence for silver resistance is rare and not fully understood.

Bacteria found within biofilms are particularly well situated to resist antimicrobial activity because the biofilm prevents the penetration of many agents and it is an ideal environment for the exchange of extra-chromosomal genetic information (Landsdown and Williams 2007) which could transfer resistant genes.

Increased use of silver in healthcare settings will certainly increase the exposure of pathogens to this metal, but whether this will lead to widespread resistance remains to be seen (Percival et al., 2005, Chopra 2007).

Allergy

A small number of people have been known to develop allergies to silver - wearing silver jewelry can lead to rashes and swelling in some individuals (Catsakis and Sulica 1978). Allergies to silver in dental implants have also been reported (Catsakis and Sulica 1978) and silver has even been implicated in the development of mouth cancer (Hougeir et al., 2006). Patch tests are used to determine the silver allergy in this group of patients, but as far as the authors are aware, there is no routine screening for silver allergy with patients who are to have a silver catheter inserted.

Manufacturer Claims

The Bard web site claims that the Bardex IC catheter is "clinically proven to reduce the incidence of nosocomial UTI", and the company has provided independent and in-house data from a wide range of studies (clinical and laboratory) which has been summarised in this document. Tyco also provided SMTL with some abstracts relating to clinical studies of the Dover Silver catheter which have also been included in this document. These are the only studies that have been provided regarding the Tyco Dover Silver product.

Table 5

The following table provides details about the two brands of “silver” urinary catheters (information provided by a representative of each company):

   Bardex IC Dover IC
Catheter material Latex silicone
Classification Medical device- Class III Medical device- Class IIb
Catheter Coating

Silver-alloy coating (containing silver, gold and palladium) applied to catheter surface, hydrogel layer on top of this

Silver ions are contained within the Hydromer coating.

Action of silver ions

Silver ions are released from catheter surface into the hydrogel (action of silver is on the surface of the device)

Silver ions are released from the hydrogel into the surrounding environment

 

The two devices differ in their composition (material used and coating methods employed) and classification to the Medical Device Directive (class "III" devices places a greater emphasis on clinical data - trials, literature reviews etc, than IIb). Although new silver-containing medical devices should now be classified as Class III devices (personal communication with the Devices section of the MHRA),  the Tyco device may have been  CE marked before this decision had been made. We do not believe the difference in classification signals any difference in the quality or efficacy of the catheters.

Tyco provided the abstracts of two clinical interventional studies (not funded by Tyco) where two different types of silver-coated catheter were compared in each. The catheters investigated were a "silver-impregnated latex catheter" and a "silver-coated all silicone catheter" (the former is the Bardex IC catheter and the latter the Dover Silver catheter - personal communication with Tyco representative). Switching the silver-coated latex catheter with the silver-coated all silicone catheter lead to a 17% and 69% reduction in UTI respectively (Caudill 205, Davis 2005). However, sufficient detail was not provided in the abstracts to explain why there was such a significant difference in UTI reduction between the two studies or why the silver-coated all silicone catheter appeared to perform better. As full technical details of the study were not provided it is difficult to comment further. The technical paper from Bacterin (Cook and Costerton 2006) indicated that the Dover Silver could prevent colonisation and cell viability for longer than the Bardex IC.

More independent clinical and laboratory studies comparing these two Foley catheters would clearly be beneficial.

Alternative strategies to reduce UTI rates in catherised patients

General improvements in catheter care

So far, attempts to completely prevent UTI have been unsuccessful, as current methods can only delay infection (Jacobsen et al., 2008). However, it is clear that simple measures to improve catheter care can reduce the risk of infection (Johnson et al., 1990, Jacobsen et al., 2008). One of the simplest measures may be to prevent overuse -  one review stated that Foley catheters should only be used as a 'last resort' for incontinence management (Nazarko 2008).

One study (Jain et al) reported that the catheterisation of 21% of patients they assessed was unnecessary and that 'continued catheterisation' was unjustified on 41% of patient days (Jain et al., 1995). They concluded that this represented 'significant overuse' of indwelling catheters. This paper suggests that more careful consideration of whether an indwelling catheter is required is likely to lead to a reduction in the numbers used which will impact the rate of UTI as well as hospital costs. Another study emphasised the necessity of reassessing each individual case to ensure that catheterisation does not continue for any longer than is required (Kassler and Barnett 2008). A recent paper published by an antimicrobial pharmacist suggested that indwelling catheters should only used if other measures (such as using incontinence pads, condom catheters, suprapubic or intermittent catheters) are not considered suitable (Moulder 2008). The author also stressed the importance of aseptic technique during catheter insertion, placing the drainage bag below the level of the bladder to prevent back flow, good hand hygiene during catheter care and only emptying the bag when it is full. Other authors have suggested similar measures (Saint and Lipsky 1999). However, some studies examining the impact of measures such as meatal care (povidone-iodine versus soap/water) and 'sterile versus clean catheterisation' have not demonstrated an improvement in UTI rate (studies reviewed by Lockwood et al. 2004).

A recent prospective study examined the impact of catheter care on CAUTI rates in 5 Japanese hospitals (Tsuchida et al., 2008). They observed catheterised patients over a period of 12 months (observing aspects of catheter care alongside signs and symptoms of CAUTI). Their main findings are summarised in the following bullet points :

  • There was a significantly greater rate of CAUTI in patients with faecal incontinence (p < 0.001). Of the 54 CAUTI detected, 51 of the patients had faecal incontinence.
  • Significantly higher levels of CAUTI were detected in hospitals with high levels of inappropriate catheter care (this included disconnected drainage systems, bags in contact with the floor, bags higher than the bladder and no cleansing of the perineal area).
  • The only hospital in the study that used silver alloy-coated catheters had the highest rate of CAUTI and the highest level of inappropriate catheter care. Reasons for this may be that users are less careful because they consider the 'anti-microbial' properties of silver-coated catheters to be sufficient to prevent infection. The results indicate that silver alloy-coated catheters are not effective unless proper catheter care is used. 

The authors of this paper concluded that faecal incontinence and catheter care are the two major factors in the fight against CAUTI.

Other advances in Technology

As well as silver-coated catheters, other Foley catheter coatings are available such as those impregnated with antibiotics (e.g. nitrofurazone). Other anti-microbial reagents such as Triclosan and urease-inhibitor compounds which may prevent encrustation are future possibilities for catheter coatings (Hamill et al., 2007). However, whether such modifications would lead to a decrease in UTI has yet to be detyermined. Other technology such as the use of electrical fields to reduce bacterial adherence may be investigated more in the future. However, with all of these modifications, the same issues as those presented for silver-coated catheters (such as cost implications and potential for selecting resistant bacteria) will still exist.

Finally, alterations to the urinary drainage system have been made (such as sealing the junction between the catheter and drainage bag or placing hydrogen peroxide in the drainage bag) but most studies have not been able to demonstrate a significant difference in UTI rate between these and conventional designs (studies reviewed by Lockwood et al. 2004).

Guidelines for the prevention of catheter-related infections

Various organisations have been evaluating the silver catheter issue in recent years.


NICE guidelines (2003)

Section 3 of the NICE (National Institute for clinical excellence) guidelines entitled "Prevention of health care-associated infections in primary and secondary health care" covers the area of urinary catheterisation (NICE 2003). One of the systematic questions in the document involves the health care worker establishing "which catheter materials cause the least irritation/encrustation/blockage" (page 104). This guidance does not mention silver-coated catheters. Their recommendations regarding the choice of catheter are as follows:

"For urethral and supra-pubic catheters, the choice of catheter material and gauge will depend on an assessment of the patient's individual characteristics and predisposition to blockage" (recommendation UC9, page 110)


EPIC guidelines (2007 and 2014)

EPIC (Evidence-based practice in infection control) guidelines regarding the prevention of health care-associated infections were issued by the Department of Health in 2001 and updated recommendations, known as EPIC2, in 2007 (which includes reviews of studies published more recently). The EPIC2 recommendations state the following:

"New evidence suggests that catheters coated with silver alloy are clinically effective in reducing the incidence of CAUTI, but many studies are of poor methodological quality. Consequently there remains inconclusive evidence to recommend their use in preference to other types of catheter at this time".

Under section 3.4 of the EPIC2 guidelines, the following recommendation was made:

"Choice of catheter material will depend on clinical experience, patient assessment and anticipated duration of catheterisation" (UC4, page S29).

Since EPIC2, new guidelines (named EPIC3) have been published (2014), which discusses recent reviews as well as the multi-centre RCT mentioned previously in this report (Pickard et al., 2012).  It concluded that there is

'.....insufficient evidence to indicate whether (silver-coated catheters) reduce the risk of CAUTI in short term catheterised patients.'

ICNA

The ICNA (Infection Control Nurse Association) have not produced any specific guidance with respect to silver-coated catheters. They refer infection control staff to the EPIC guidance, as described above (communication with the South West representative of the ICNA). In the USA, the CDC (Centres for Disease Control and Prevention) have produced a document entitled "Guideline for prevention of catheter-associated urinary tract infection" (CDC, 1981) but it does not deal with the use of silver-coated catheters. The Scottish Intercollegiate Guidelines Network (SIGN) have provided guidance on the management of urinary incontinence in primary care (SIGN 2004)but this does not include recommendations concerning the use of silver-coated catheters either. In 2004, the Association of Continence Advice issued notes on good practice, but again, no specific guidance on the use of silver-coated catheters has been issued (communication with ACA Chair).

Conclusion

Some studies reviewed indicate that the use of silver-coated urinary catheters may be beneficial in the prevention of UTIs in short-term catheterised patients, although there are serious concerns regarding the quality of many of the studies reviewed.
Most of the studies have methodological problems which make it difficult to draw any conclusions on their clinical effects. In particular, most focus on bacterial colonisation as opposed to clinical symptoms when assessing the practical effectiveness of these products. No study to date has been able to demonstrate that silver-coated catheters significantly reduce clinically significant infections such as blood steam and kidney infections arising from a UTI.

The sampling methods for the urine are frequently flawed, and the use of pre-post studies is well known to skew the results of trials in favour of the experimental arm compared to the historically controlled arm of the study. Very few studies used true random allocation of treatments, nor did most of them discuss important criteria such as post randomisation exclusions. The poor choice of comparator products in many of the studies makes it impossible to determine whether it was the silver or other features of the catheter which reduced bacterial levels.

The most compelling study (due to its high quality design and large sample size), which aimed to address issues that previous studies omitted, concluded that silver-coated catheters were neither clinically beneficial or cost effective (HTA, Pickard et al., 2012).

Of note is the fact that, apart from the Rapid Review Panel, most organisations who could make recommendations about this subject have refrained from recommending silver catheters. The most recent EPIC guidelines conclude that there is 'insufficient evidence to indicate whether (silver-coated catheters) reduce the risk of CAUTI in short term catheterised patients' (EPIC3, 2014).

The authors of this review conclude that there is good quality evidence to suggest that silver-coated catheters do not perform any better than conventional catheters in reducing CAUTI, and are not cost effective. 


Appendices

Table A

Interventional Studies

Study

 

Description of Study Sample

Duration of study  

Description of control Catheter

Description of silver catheter

Reduction in the rate of UTI (% decrease where given)

UTI Definition*  

Carlton '96
(abstract)
Hospital-wide 3 months silicone-coated latex No detail Non significant reduction U1
Lucente '97
(abstract)
ICU departments 4 months No detail Bardex IC 51% (Medical ICU) 56% (Surgical ICU) 46% (Coronary ICU) U
White '97
(abstract)

Hospital-wide 6 months No detail No detail 56.6% U
Barron '98
(abstract)
Hospital-wide (220 bed) 7 months No detail Bardex IC 69% U
Lettau '98
(abstract)
Hospital-wide 6 months No detail Bardex IC 55% U
Poduska '98
(abstract)
Hospital-wide 4 months No detail Bardex IC 53.5% U

Ramirez '98
(abstract)
2 hospitals 3 month No detail No detail 56% U
Accuntius '99
(abstract)
Hospital-wide No detail No detail No detail No reduction U1
Bologna '99
(paper)
5 ICUs (108 beds) Up to 12 months Standard latex Bardex IC Non significant reduction

micro-biological assessment and chart review1

Hernandez '99
(abstract)
Hospital-wide 3 years No detail No detail 55.6% U
Collins '99
(abstract)
1 hospital 3 months No detail Bardex IC 29.5% U
Newton '99
(abstract)
1 hospital No detail No detail Bardex IC Non significant reduction U1
Baker '00
(abstract)
Hospital-wide 3 months No detail Bardex IC 55.2%

positive urine culture after 72h

Adams '01
(abstract)
1 hospital 3 months No detail Bardex IC 35% U
Helget '01
(abstract)
1 hospital (8 wards) 6 months No detail No detail 50% U
Peninger '01
(abstract)
Areas of 8 hospitals 3 months Non-coated No detail 43% U
Lai '02
(paper)
Hospital-wide 5 months Non-coated Bardex IC 45% U
Newton '02
(paper)
1 Hospital (all acute burns patients) 1 year Standard latex Bardex IC 39% U
Madeo et al. 2004 (paper)

188 patients No details Conventional catheter Bard silver alloy coated catheter 11%

105/ml count with 2 or less spp and present with classical signs/symptoms

Rupp '04
(paper)
10 wards 2 years Non-coated latex Bardex IC 57% U1
 Bystrom, '05 (abstract) No detail 5 months no detail Dover silver catheter 73.8%  U1
Gentry 2005
(paper)

133 patients 1 month No detail Bardex IC 48.5 %  >105 organisms/ml and a range of clinical symptoms including fever and loin pain
McArdle
'05
(Abstract)
Hospital-wide 4 months Non silver-coated latex Dover Silver catheter 75% U1
Seymour '06 (paper) Hospital-wide 2.5 months No detail Bardex IC 69.9% >104cfu/ml and 2 symptoms (if diagnosed by a physician) (information via communication with author)
Srinivasan '06
(paper)
1 hospital 10 months All silicone Lubri-sil IC (Bard-silver coated silicone) Non significant reduction urine culture
Kassler and Barnett 2008 (paper) 42 bed rehabilitation hospital 6 months 100% silicon 100% silicon, 'ionic silver' 100% Positive urine culture

 *Refers to how the authors defined UTI. 'U' means that the definition was unspecified in the paper. U1 refers to studies that used the National Nosocomial Infections Surveillance System (Centre for Disease Control and Prevention, USA) to define UTIs. However, this system includes definitions of both symptomatic and asymptomatic UTI and most studies did not specify whether the results they provided referred to infections that satisfied both criteria (i.e. positive urine culture plus signs and symptoms) or not. Therefore, it is not possible to differentiate between symptomatic and asymptomatic infections in most of these studies.

Table B

Randomised Studies

Study

Description of

study sample

Duration of study

Discription of

Control Catheter 

Description of

silver catheter

Difference in UTI rates

between control and

experimental groups

UTI definition*

Lundeberg '86
(letter)
102 patients No detail Standard No detail Significant >100 organisms /ml
Johnson et al '90 (paper)


482 patients 1 year  All-silicone

silicone catheter with silver-oxide coating

Not significant (overall) 

2 consecutive cultures of >102cfu or one culture of >105cfu

Liedberg '90a
(paper)
120 patients 6 days per patient Teflon-coated latex No detail Significant  >105organisms/ml
Liedberg '90b (study
1) (paper)
90 patients 5 days per patient Non-coated No detail Significant  >105organisms/ml
Liedberg '90b
(study 2)
(paper)
90 patients 5 days per patient Hydrogel-coated No detail Not significant >105organisms/ml 
Nakada '96
(abstract)
12 patients 14 days per patient Silicone No detail Not significant U
 Garcia '99
(abstract)
169 patients No detail No detail No detail Significant U
Verleyen '99 (study 1)
(paper)
180 patients 5 days per patient Uncoated latex Bardex IC Significant >105organisms/ml 
Verleyen '99 (study 2)
(paper)
35 patients 14 days per patient Silicone Bardex IC Not significant >105organisms/ml  
Karchmer '00
(paper)
1 hospital  12 months overall

Latex based, silicone elastomer coated

Bardex IC Non-Significant Various symptoms
Thibon '00
(paper)

Approx. 200

patients

24 months overall

(10 days per patient)

Silicone No detail Not significant >105organisms/ml  
Liedberg (unknown date)
(abstract)

Approx. 175

patients

Up to 21 days per patient

Hydrogel coated Bardex IC Significant >105organisms/ml   
Thomas (unknown date)
(abstract)
12 hospitals No detail Standard No detail Significant U

Pickard et al., 2012 (HTA study)

Over 6000 patients from 24 hospitals

Approximately 1 year overall (up to 6 weeks follow-up per patient)

PTFE-coated latex Bardex IC Not significant

>105organisms/ml plus various symptoms

 * 'U' means the definition of UTI was unspecified in the paper.

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