A Prospective Trial of a Novel, Silicone‐Based, Silver‐Coated Foley Catheter for the Prevention of Nosocomial Urinary Tract Infections
Objective. To evaluate the efficacy of silicone‐based, silver ion–impregnated urinary catheters in the prevention of nosocomial urinary tract infections (NUTIs).
Design. Prospective, crossover study to compare the efficacy of a silicone‐based, hydrogel‐coated, silver‐impregnated Foley catheter with that of a silicone‐based, hydrogel‐coated catheter in the prevention of NUTIs.
Setting. Adult medical and surgical wards of a university teaching hospital.
Results. A total of 3,036 patients with catheters were evaluated; 1,165 (38%) of the catheters were silver impregnated, and 1,871 (62%) were not silver impregnated. Study groups were not identical; there were more men, a shorter duration of catheterization, and fewer urine cultures per 1,000 catheter‐days in the silver catheter group. The rate of NUTIs per 1,000 Foley‐days was 14.29 in the silver catheter group, compared with 16.15 in the nonsilver catheter group (incidence rate ratio, 0.88; 95% confidence interval, 0.70‐1.11; 
). The median length of catheterization prior to the onset of a urinary tract infection (ie, exposure time) was 4 days for each group. There were no differences in the recovery of gram‐positive, gram‐negative, or fungal organisms in NUTIs. In a multivariate survival analysis, no factors, including silver catheters, were protective against NUTI.
Conclusions. Unlike previous trials of latex‐based, silver ion–impregnated Foley catheters, we found that silicone‐based, silver‐impregnated Foley catheters were not effective in preventing NUTIs; however, this study was affected by differences in the study groups. Prospective trials remain important in assessing the efficacy and cost‐effectiveness of new silver‐coated products.
Received May 5, 2004; accepted October 22, 2004; electronically published January 6, 2006.
Urinary tract infections (UTIs) are the most common type of healthcare‐associated infections, accounting for up to 40% of all nosocomial infections.1 Although UTIs are generally minor and asymptomatic,2 bacteriuria is an independent predictor of mortality among hospitalized patients,3 and as many as 15%‐17% of nosocomial bloodstream infections (BSIs) are secondary to UTIs.4‐6 Nosocomial UTIs (NUTIs) may add $356‐$3,803 to direct hospital costs7,8 and as much as $500 million to healthcare costs in the United States each year9 and may serve as a reservoir for highly resistant bacteria.10‐12
Eighty percent of NUTIs are associated with the use of indwelling urinary catheters.13,14 Previous studies of latex‐based catheters have demonstrated that a silver alloy coating is effective in reducing the incidence of catheter‐associated NUTIs.9,15,16 Because of problems associated with the use of latex in healthcare settings, we conducted the first large, prospective trial of a non–latex‐based, silver alloy–coated urinary catheter.
Methods
Setting
This 24‐month trial was conducted at Johns Hopkins Hospital, a 1,000‐bed, tertiary‐care hospital in Baltimore, Maryland. Adult inpatients who had indwelling Foley catheters for >48 hours were eligible for enrollment. Patients admitted to psychiatry, obstetrics, and gynecology services were not included, because of the low incidence of catheter use among these patients. In addition, we excluded patients admitted to the hospital oncology center, because of the high incidence of antibiotic use in that population. During the 14‐month baseline period, all silicone catheters (Lubri‐Sil, CR Bard) were used throughout the hospital, which has adopted a goal of using no latex products. During the 10‐month intervention period, the catheter supply for the units involved in the study was changed to silver alloy– and hydrogel‐coated silicone Foley catheters (Lubri‐Sil IC, CR Bard), which are coated with silver alloy on both the external and internal surfaces. Supply was also changed for the operating rooms and emergency department, because the majority of Foley catheters are placed while patients are in these locations. The intervention period started later than intended because of difficulties with changing the catheter supply. The study was approved with a waiver of informed consent by the Johns Hopkins University institutional review board.
Data Collection
Each day, a census of patients in each study unit was uploaded into a personal data assistant (Palm Pilot V, Palm). Research staff members reviewed bedside charts in the wards, to determine whether newly admitted patients had indwelling catheters and whether previously enrolled patients still had an indwelling catheter or if the catheter had been changed. To ensure correct assignment, the catheter was inspected to determine whether it was silver coated. Information was also collected on whether the Foley catheter was preconnected to the collection bag (“preconnected Foley system”) or not (“component Foley system”). All patient information was collected on the personal data assistant and then downloaded into a computer database. Each day, the database queried the microbiology computer system to recover results of urine cultures for patients enrolled in the study. To ensure that only catheter‐related NUTIs were included, the database was programmed to retrieve only the results of urine cultures obtained during a period that started 48 hours after the catheter was inserted and ended 7 days after catheter removal. Any patient who had evidence of a UTI on the basis of urine culture results during the 7 days before catheter insertion was excluded from the study. Blood culture results for all patients included in the study were also obtained, as was information on the sex of each patient and on the hospital service to which each patient was admitted.
NUTIs were identified by use of criteria set forth by the Centers for Disease Control and Prevention.17 Because all patients enrolled had an indwelling catheter inserted within 7 days of the urine culture, cases of asymptomatic bacteriuria were counted as UTIs, in accordance with the Centers for Disease Control and Prevention definition. For patients who had different types of catheters placed during the hospital stay, the infection was attributed to the catheter that had been in place 48 hours before the culture was obtained. A BSI was considered to be secondary to the UTI if the same organism was recovered in both sites during a 48‐hour period. Rates of infection were calculated as both the number of infections per 100 catheters inserted and as the number of infections per 1,000 catheter‐days.
As part of a separate study to collect information on the costs of NUTIs, charts for a randomly selected subset of patients with UTIs were reviewed by an infectious diseases attending specialist, and information on antibiotic treatment was recorded. Antibiotics were classified as being for treatment of a UTI only if there was documentation in a provider’s note that the antibiotics were for the treatment of the UTI and not for any other infection.
Data Analysis
It was estimated that, if 20% of patients developed a catheter‐associated UTI, a sample size of 1,497 patients per catheter type would be sufficient to detect a 20% reduction in the incidence of UTIs at the 5% significance level, with 80% power. Data were compared using the χ2 test for categorical variables and the Wilcoxon rank sum test for nonnormally distributed continuous variables. Univariate analysis was performed with Poisson regression to compare incidence rates. Finally, a multivariate survival analysis was performed with the following variables: patient's sex, hospital service into which the patient was admitted, and type of catheter inserted. All data were analyzed using Stata software (version 7.0, StataCorp).
Results
A total of 3,036 patients with catheters were enrolled in the trial: 1,165 had silver catheters (“silver group”), and 1,871 had nonsilver catheters (“nonsilver group”). As shown in Table 1, in the silver group, there were significantly more men and a significantly larger percentage of patients whose catheters were inserted while they were in a medical ward. The median duration of catheterization was 1 day shorter for the silver group, a difference that was statistically significant (4 days for the silver group vs 5 days for the nonsilver group; 
).
There were a total of 334 NUTIs detected, 116 in the silver group (cumulative incidence, 10.0 NUTIs per 100 catheters) and 218 in the nonsilver group (cumulative incidence, 11.7 NUTIs per 100 catheters). The incidence rates were 14.3 NUTIs per 1,000 Foley‐days in the silver group and 16.2 NUTIs per 1,000 Foley‐days in the nonsilver group (incidence rate ratio, 0.88; 95% confidence interval [CI], 0.70‐1.11; 
) (Table 2). More urine cultures were performed for patients in the nonsilver group (68.92 cultures per 100 Foley‐days) than for patients in the silver group (61.49 cultures per 1,000 Foley‐days; incidence rate ratio 1.12, 95% CI, 1.12‐1.18). Although UTI rates were consistently lower in the silver group, the differences were not statistically significant. When the data were analyzed to compare UTIs that occurred in the intensive care units with those that occurred in non–intensive care unit locations, rates were lower in the silver group, but, again, differences were not statistically significant (Table 2).
Results comparing UTI rates between the preconnected and component systems were mixed. For preconnected systems, the cumulative incidence of UTIs per 100 catheters was significantly lower for the silver group, but the incidence rate per 1,000 Foley‐days was not (Table 2). Conversely, among component Foley systems, the rates were higher for patients in the silver group, but, again, the difference was statistically significant with the cumulative incidence but not with the incidence rate (Table 2). The median length of catheterization prior to the onset of a UTI (ie, exposure time) was 4 days in each group. There were no significant differences in UTI rates for catheters placed in medical wards, surgical wards, or other locations.
In the univariate survival analysis, only female sex was a significant risk factor for the development of a UTI (hazard ratio, 2.34; 95% CI, 1.86‐2.96). Use of a silver catheter was protective, but not significantly so (hazard ratio, 0.92; 95% CI, 0.73‐1.15). Likewise, in the multivariate survival analysis, female sex was the only significant, independent risk factor for the development of a UTI (hazard ratio, 2.26; 95% CI, 1.78‐2.89), and no factors were protective.
There were a total of 7 urinary catheter–associated BSIs (0.4% of all catheters and 3% of all UTIs) in the nonsilver group, compared with 9 (0.7% of all catheters and 8% of all UTIs) in the silver group. The BSI incidence rate per 1,000 Foley‐days was 1.11 in the silver group and 0.52 in the nonsilver group (rate ratio, 2.13; 95% CI, 0.96‐4.76; 
).
Overall, gram‐negative organisms accounted for 45% of infections, gram‐positive organisms for 36% of infections, and yeast for 18% of infections (Table 3). There were no significant differences between the nonsilver and silver groups with respect to the types of organisms that were recovered.
Discussion
NUTIs remain the most common healthcare‐associated infections and have been shown to contribute to adverse outcomes, increased hospital costs, and the development of resistance to antimicrobials. In this study of a silicone‐based, silver‐coated urinary catheter, UTI rates were lower among patients who received the silver catheters, but the reduction was not significant in either the ward or intensive care unit setting. In a multivariate analysis, the use of silver‐coated catheters did not delay the onset of NUTIs, nor was it protective against NUTIs.
Since the introduction of the closed drainage system in the 1950s,18,19 numerous measures to prevent NUTIs have been introduced, but none has proven to be effective.20 More recently, advances in technology have enabled the development of Foley catheters that are coated with antimicrobial substances. Foley catheters coated with systemic antibiotics have shown efficacy in vitro21,22 and in one clinical trial.23 However, limited efficacy, combined with the potential development of antimicrobial resistance, has lessened enthusiasm for these catheters.
Silver ions are known to have broad‐spectrum antimicrobial activity24 and may not confer antibiotic cross‐resistance. In vitro studies of silver‐coated urinary catheters have shown reductions in bacterial adherence.25 Initial studies of silver oxide–coated catheters did not show significant decreases in UTIs,26,27 and these catheters are no longer marketed in the United States. In contrast, trials of Foley catheters coated with silver alloy have been relatively favorable. Although not all trials have been prospective, 4 of the 6 did show a significant reduction in bacteriuria,9,15,16,28 1 showed mixed results,29 and 1 showed no benefit.30 The 2 largest trials 9,15 did show favorable results, and 2 meta‐analyses have shown clinical and economic benefits of silver alloy–coated catheters.31,32
To date, all trials of silver‐coated Foley catheters have used latex‐based products. However, with the growing and serious problems of latex allergies,33,34 many hospitals are adopting “latex‐free” policies, necessitating the development of silicone‐based Foley catheters. It is more difficult to bind silver alloy to silicone than to latex, which necessitates a more strenuous pretreatment and primer coating of the silicone catheters. Differences in bacterial adhesion between silicone‐ and latex‐based silver‐coated Foley catheters were noted in 1 in vitro study.25
In contrast to the trials of silver‐latex catheters, we found no significant reduction in the incidence of NUTIs with a silver‐silicone Foley catheter, compared with a silicone catheter. The only statistically significant differences between the UTI rates for the 2 catheters were seen in some subset analyses of preconnected and component Foley systems. It is not clear why the analysis of the different Foley systems yielded different results.
The incidence rate of BSIs associated with the use of urinary catheters was higher in the silver group, though not significantly so. It is not known whether the silver coating caused increased urethral irritation, which might have increased the risk of dissemination of bacteria. However, urethral irritation has not been commonly reported with silver‐coated Foley catheters, and we received no reports of increased irritation in our study. Although the trend is concerning, these data must be interpreted with caution, because the study was not sufficiently powered to assess secondary BSIs. This higher incidence of BSIs may also be explained by the fact that there were more men in the silver group, because men have been shown to be at higher risk to develop BSIs secondary to UTIs.35
Despite the prospective design of this trial, our study was limited by the fact that the groups were not identical. There were more men in the silver group, the duration of catherization was 1 day shorter in the silver group, and more urine cultures were performed for the nonsilver group. However, all of these confounding factors should have biased results toward showing a beneficial effect of the silver catheters. The first 2 factors would have lowered the UTI rate in the silver group, and the third factor should have increased the UTI rate in the nonsilver group. A higher percentage of the silver catheters were placed while patients were in medical wards, but since there were no significant differences in UTI rates on the basis of where the catheters were placed, this difference should not have affected the results.
Likewise, the groups were not identical in terms of the number of patients enrolled, with 62% of them having nonsilver catheters. Problems with changing the catheter supply and distribution delayed the onset of the intervention period, resulting in only 10 months of silver catheter use. Review of the data at the 24‐month planned termination point revealed that the differences between the groups were so small that attaining the planned enrollment still would not lead to a significant difference between the groups, and a decision was made to terminate the study at that time.
Another limitation that potentially biased the results toward the null hypothesis is the fact that we did not perform daily urine cultures on all patients. Some previous studies of silver‐impregnated catheters have used daily urine cultures,2 whereas others have not.9 We believe that the use of only clinically obtained urine cultures strengthened the results of the present study, because we were more likely to detect only clinically relevant UTIs, which is an end point of much greater interest to most clinicians.
Another important limitation of our study was the fact that, like most other large studies of silver‐coated urinary catheters,9,15 we included the Centers for Disease Control and Prevention definition of asymptomatic bacteriuria in a patient with a catheter in our definition of UTI. It is not known how many of these patients had signs of infection, and, hence, it is impossible to know whether or not the silver catheters reduced the incidence of symptomatic UTIs.
Likewise, we do not know exactly how many of the UTIs in each group were treated by healthcare providers. Because we limited our data collection to urine samples that were ordered by treating providers, there was presumably a suspicion of a UTI. Review of a subset of cases revealed that UTIs were treated in 44% of cases, indicating that almost half of the UTIs were clinically relevant. However, this is likely a significant underestimate, because 87% of patients with UTIs were also receiving antibiotics for another reason. Thus, in the majority of cases, patients were receiving antibiotics that might have treated the infecting pathogen found by urine culture. Furthermore, we do not know how many patients were receiving antibiotics that might have protected them from a UTI.
The incidence rate of UTIs in our study was lower than the 20% that had been anticipated, and, thus, our study had only 50% power to detect a 20% reduction in NUTIs. However, the observed reduction was only 12%, and, as mentioned before, this reduction was likely an overestimate. Even if this reduction had been statistically significant, it is not clear that such a modest reduction would justify the increased cost of the silver catheters, because previous studies, in which cost benefits were demonstrated in association with the use of silver catheters, used a 30%‐40% relative reduction in UTI rates.9,32
There is growing enthusiasm for the ability of silver‐coated medical products to reduce the incidence of nosocomial infections. These products appear to be quite safe for patients, and, given the growing issues of antibiotic resistance, silver coating would appear to be preferable to antibiotic coating, because, even if resistance does develop, it does not appear to compromise the use of most antibiotics. Previous studies have demonstrated that silver‐coated central venous catheters36,37 and Foley catheters9,15,16,28 can reduce the rates of nosocomial BSIs and UTIs respectively. In vitro data have also shown promise for silver‐coated endotracheal tubes.38 Thus, it appears that this technology does hold promise, but the findings of our study indicate that more research is needed in this area. Although the all‐silicone silver‐coated catheter used in the present study seemed to be as effective as its latex counterpart in vitro,25 this similarity was not seen in vivo. Thus, even the minor in vitro differences that were observed resulted in a clinically significant difference. Rather than cast doubt on the efficacy of silver‐coating technology, we believe that our study should serve as a cautionary note that not all silver products are the same and that clinical trials of new silver‐coated products remain critically important. Future studies should use a prospective study design to help accurately determine the efficacy of new, silver‐coated products.
Acknowledgments
We thank Tim Decapite for assistance with data collection. The study was funded in part by a grant from CR Bard Medical, Covington, GA.
Disclosure statement: Arjun Srinivasan, Tobi Karchmer, and Trish Perl have received grant support from CR Bard. Drs. Karchmer and Perl have been speakers for CR Bard.
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