Chapter 15. Prevention of Nosocomial Urinary Tract Infections

Sanjay Saint, M.D., M.P.H.
University of Michigan School of Medicine

Background

Many hospitalized patients require the placement of indwelling urinary catheters for days or even weeks at a time.¹ Only a minority of patients develop urinary tract infections because of the presence of these devices,^2,3 but the frequency of their use produces substantial overall morbidity for patients and costs to the healthcare system. Urinary tract infections (UTIs) account for up to 40% of nosocomial infections,^4,5 with urinary catheter-related infections causing the vast majority of nosocomial UTIs.⁶ Each hospital-acquired UTI adds approximately $675 to the costs of hospitalization. When bacteremia develops, this additional cost increases to at least $2800.²

Because of the substantial complications and costs associated with the use of urinary catheters, a number of practices have been evaluated in an effort to reduce the incidence of urinary catheter-related infections. This chapter reviews the evidence supporting the use of silver alloy coated urinary catheters, and, because of its similarity, the recently described practice of using urinary catheters impregnated with the antibiotic combination of minocycline and rifampin. Subchapter 15.2 reviews the evidence supporting the use of suprapubic catheters as an alternative to urethral catheters.

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Subchapter 15.1. Use of Silver Alloy Urinary Catheters

Practice Description

Silver is a highly effective antibacterial substance, which can be applied to various types of catheters. (See Subchapter 16.2 for a discussion of intravascular catheters coated with a combination of silver sulfadiazine and chlorhexidine). Multiple studies have suggested that silicone urethral catheters coated with hydrogel and silver salts reduce the risk of developing bacteriuria, compared with standard latex urethral catheters (Foley catheters). As shown in a recent meta-analysis, this benefit applies to catheters coated with silver alloy (which are coated on both internal and external surfaces of the catheter), but not silver oxide (which are coated on the external catheter surface only). Consequently, this chapter focuses only on studies evaluating silver alloy catheters, and the use of catheters coated with antimicrobials.⁸

Prevalence and Severity of the Target Safety Problem

Almost one million episodes of nosocomial UTI occur annually in the United States.⁹ Each year approximately 96 million urethral catheters are sold worldwide. Of these, nearly 25% are sold in the United States.³ The daily rate of bacteriuria in catheterized patients ranges from 3 to 10%, with the incidence directly related to the duration of catheterization.⁴ Among patients with bacteriuria, 10 to 25% will develop symptoms of local urinary tract infection,^2,10 such as suprapubic or flank pain. The development of catheter-related bacteriuria carries with it a 2.8-fold increased risk of death, independent of other co-morbid conditions and disease severity.^11,12 Bacteremia results from catheter-related bacteriuria in approximately 3% of patients, and invariably represents a serious complication.^2,3

Beyond the morbidity and mortality associated with indwelling catheters, catheter-related infection results in substantially increased healthcare costs. Data suggest that each episode of hospital-acquired symptomatic catheter-related UTI costs an additional $676, and each episode of catheter-related nosocomial bacteremia costs a minimum of $2836.²

Estimates from one university hospital, based on data from almost 20 years ago, were that hospital-acquired UTI led to approximately $204,000 in additional expenses per year.¹³ More recent data are unavailable, but the institutional costs attributable to catheter-related infection are clearly substantial.

Opportunities for Impact

Since catheter-related UTI is the leading cause of nosocomial infection in the United States and is associated with increased morbidity and costs, any intervention that reduces the incidence of catheter-related UTI is potentially important. Currently, it is unknown what proportion of patients with indwelling catheters receives silver alloy catheters, however it is likely to be the minority.

Study Designs

As shown in Table 15.1.1, a meta-analysis which included 4 randomized clinical trials,^14-17 compared the efficacy of silver catheters with standard, non-coated catheters. Five additional studies^18-22 have appeared since publication of this meta-analysis. In 3 of these studies,^18,20,22 the patient represented the unit of analysis. Another study employed a randomized crossover design (Level 1), randomizing wards rather than individual patients.¹⁹ The final study used a prospective, before-after design at 5 different hospitals (Level 2).²¹

The patient populations for these studies included patients on various hospital services including urology, internal medicine, neurology, and the intensive care unit. In general, the studies included patients expected to be catheterized for at least 2 days. Since the patients resided in acute care hospitals rather than extended care centers, most were catheterized for 10 days or less. Several studies specified that patients given concomitant antibiotics were excluded.^15-18

Study Outcomes

The individual trials and the meta-analysis focused primarily on the surrogate outcome of bacteriuria (Level 2). The definition of bacteriuria varied somewhat in the studies. However, low-level growth from a catheterized specimen (i.e., 10² colony forming units (CFU) /mL) usually progresses within days to concentrations of greater than 10⁴ CFU/mL unless antibiotic therapy is given.²³ Unfortunately, none of the studies was adequately powered to detect a significant difference in the clinically more important outcomes of catheter-related bacteremia or death. Though bacteriuria is a surrogate endpoint,²⁴ it is probably appropriate to use since it is a component of the only causal pathway in the disease process between catheterization and an important clinical outcome (e.g., symptomatic UTI or catheter-related bacteremia). One study did report differences in secondary bloodstream infections.¹⁹

Evidence for Effectiveness of the Practice

The 4 clinical trials^14-17 of silver alloy catheters included in the meta-analysis⁷ all showed a significant reduction in the development of catheter-associated bacteriuria. As shown in Table 15.1.1, studies published after the meta-analysis have reported more mixed results. Several of the studies have shown a statistically significant benefit of silver alloy catheters, but with a smaller relative risk reduction compared to that reported in the meta-analysis.^19,21,22 However, one study failed to find a significant benefit associated with silver alloy catheters,²⁰ and another found benefit from silver alloy catheters in those given such catheters for about 5 days, but not in those given the catheter for 14 days.¹⁸ A formal update of the previous meta-analysis would be helpful, but is beyond the scope of the current report.

Potential for Harm

There is likely minimal harm from the use of silver alloy urinary catheters. The one theoretical harm involves the development of antimicrobial resistance. However, since silver is not used systemically in the form of an antimicrobial agent for treatment, the clinical significance of antimicrobial resistance to silver is unclear.

Costs and Implementation

Each silver alloy urinary catheter tray costs about $5.30 more than a standard, non-coated urinary catheter tray. However, a recent economic evaluation indicates that when all the clinical and economic costs are accounted for, silver alloy urinary catheters may provide both clinical and economic benefits in patients receiving indwelling catheterization for 2 to 10 days.³ It should be noted that one of the major assumptions made in the economic evaluation is that a certain proportion of patients with bacteriuria develop the clinically important (Level 1) outcomes of symptomatic UTI or bacteremia. The economic analysis did not assign any costs to bacteriuria but did assign costs if patients developed these clinically important outcomes. Additionally, several of the very recent efficacy studies of silver alloy catheters^19,21,22 were not included in the economic analysis. A clinical study, adequately powered to detect both meaningful clinical and economic endpoints, would confirm the results of this economic evaluation that relied on modeling techniques. The overall cost of universal implementation of silver alloy catheters is unclear.

Comment

The data supporting the use of silver alloy urinary catheters to reduce urinary catheter-related bacteriuria is reasonably strong. As noted, the incidence of bacteriuria, while not extremely high, carries a high morbidity. It remains unclear whether silver alloy urinary catheters will also lead to decreases in the clinically more important outcomes of catheter-related bacteremia and mortality. Continuing investigation into the impact of silver alloy catheters on these important outcomes and their effect on the emergence of antibiotic resistance should be pursued. Of note, catheters coated with antibacterial substances other than silver have also been evaluated. A recent randomized study⁸ found that patients who received antimicrobial-impregnated catheters coated with minocycline and rifampin had significantly lower rates of gram-positive bacteriuria than a control group given standard, non-coated catheters (7.1% vs. 38.2%; p <0.001). Both control and intervention groups had similar rates of gram-negative bacteriuria and candiduria (Table 15.1.1). However, the theoretical risk of developing antimicrobial resistance to minocycline and/or rifampin (2 agents occasionally used systemically) may limit the use of catheters coated with these antibiotics.

Table 15.1.1. Studies of silver alloy and antibiotic-impregnated urethral catheters*

Study	Description	Design, Outcomes	Results: Odds or Risk of Bacteriuriaa (unless otherwise noted)
Saint, 19987	Meta-analysis of 4 randomized controlled trials (n=453) of silver alloy vs. uncoated urinary catheters	Level 1A, Level 2	OR 0.24 (95% CI: 0.11-0.52)
Maki, 199822	Prospective, randomized, double-blind trial of silver alloy (n=407) vs. standard Foley (n=443) catheters	Level 1, Level 2	RR 0.74 (95% CI: 0.56-0.99)
Verleyen, 199918	Prospective, randomized study of medium-term catheterization with silver alloy (n=18) vs. silicone (n=17) catheters after radical prostatectomy	Level 1, Level 2	After 14 days, 50.0% vs. 53.3% (p=NS)
	Prospective, randomized study of short-term catheterization with silver alloy (n=79) vs. latex (n=101) catheters	Level 1, Level 2	On day 5, 6.3% vs. 11.9% (p<0.003)
Bologna, 199921	Prospective, blinded study of silver alloy vs. standard latex Foley catheters in 5 hospitals. Baseline period ranged from 3-12 months (mean, 8 months); intervention period ranged from 7-19 months (mean, 10 months)	Level 2, Level 1	Unadjusted infection rate: 4.5 vs. 7.1 infections per 1000 catheter days (p<0.01) Adjusted infection rate: 4.9 vs. 8.1 infections per 1000 catheter days (p=0.13)
Karchmer, 200019	12-month randomized crossover trial of catheter-associated urinary tract infections in patients with silver-coated and uncoated catheters. The ward was the unit of analysis. A cost analysis was also conducted.	Level 1, Level 1	Infection rate: 2.66 vs. 3.35 infections per 1000 patient-days, RR 0.79 (95% CI: 0.63-0.99) Infection rate: 1.10 vs. 1.36 infections per 100 patients, RR 0.81 (95% CI: 0.65-1.01) Infection rate: 2.13 vs. 3.12 infections per 100 catheters, RR 0.68 (95% CI: 0.54-0.86) Estimated hospital cost savings with silver-coated catheters: $14,456 to $573,293
Thibon, 200020	Multicenter, prospective, randomized, double-blind trial of silver alloy (n=90) vs. standard (n=109) catheters in patients requiring catheterization for >3 days	Level 1, Level 2	After 10 days, 10% vs. 11.9% OR 0.82 (95% CI, 0.30-2.20)
Darouiche, 19998	Multicenter, prospective, randomized, blinded trial of medium-term catheterization (mean, 14 days) with minocycline-rifampin impregnated (n=56) vs. silicone (n=68) catheters after radical prostatectomy	Level 1, Level 2	Patients took longer to develop bacteriuria with antimicrobial- impregnated catheters than control catheters (p=0.006 by the log-rank test) Overall bacteriuria at day 7: 15.2% vs. 39.7% (p<0.05) Overall bacteriuria at day 14: 58.5% vs. 83.5% (p<0.05) Gram-positive bacteriuria: 7.1% vs. 38.2% (p<0.001) Gram-negative bacteriuria: 46.4% vs. 47.1% (p=NS) Candiduria: 3.6% vs. 2.9% (p=NS)

* CI indicates confidence interval; NS, not statistically significant; OR, odds ratio; and RR, relative risk.

^a Results are reported as intervention group (silver alloy or minocycline/rifampin catheter) vs. control group.

References

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2. Saint S. Clinical and economic consequences of nosocomial catheter-related bacteriuria. Am J Infect Control 2000;28:68-75.

3. Saint S, Veenstra DL, Sullivan SD, Chenoweth C, Fendrick AM. The potential clinical and economic benefits of silver alloy urinary catheters in preventing urinary tract infection. Arch Intern Med 2000;160:2670-2675.

4. Haley RW, Hooton TM, Culver DH, Stanley RC, Emori TG, Hardison CD, et al. Nosocomial infections in U.S. hospitals, 1975-1976: estimated frequency by selected characteristics of patients. Am J Med 1981;70:947-959.

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7. Saint S, Elmore JG, Sullivan SD, Emerson SS, Koepsell TD. The efficacy of silver alloy-coated urinary catheters in preventing urinary tract infection: a meta-analysis. Am J Med 1998;105:236-241.

8. Darouiche RO, Smith JA, Jr., Hanna H, Dhabuwala CB, Steiner MS, Babaian RJ, et al. Efficacy of antimicrobial-impregnated bladder catheters in reducing catheter-associated bacteriuria: a prospective, randomized, multicenter clinical trial. Urology 1999;54:976-981.

9. Kunin CM. Urinary Tract Infections: Detection, Prevention, and Management. 5th ed. Baltimore: Williams and Wilkins; 1997.

10. Tambyah PA, Maki DG. Catheter-associated urinary tract infection is rarely symptomatic: a prospective study of 1,497 catheterized patients. Arch Intern Med 2000;160:678-682.

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12. Platt R, Polk BF, Murdock B, Rosner B. Reduction of mortality associated with nosocomial urinary tract infection. Lancet 1983;1:893-897.

13. Krieger JN, Kaiser DL, Wenzel RP. Nosocomial urinary tract infections: secular trends, treatment and economics in a university hospital. J Urol 1983;130:102-106.

14. Lundeberg T. Prevention of catheter-associated urinary-tract infections by use of silver-impregnated catheters [letter]. Lancet 1986;2:1031.

15. Liedberg H, Lundeberg T. Silver alloy coated catheters reduce catheter-associated bacteriuria. Br J Urol 1990;65:379-381.

16. Liedberg H, Lundeberg T, Ekman P. Refinements in the coating of urethral catheters reduces the incidence of catheter-associated bacteriuria. An experimental and clinical study. Eur Urol 1990;17:236-240.

17. Liedberg H, Lundeberg T. Prospective study of incidence of urinary tract infection in patients catheterized with bard hydrogel and silver-coated catheters or bard hydrogel-coated catheters [abstract]. J Urol 1993;149:405A.

18. Verleyen P, De Ridder D, Van Poppel H, Baert L. Clinical application of the Bardex IC Foley catheter. Eur Urol 1999;36:240-246.

19. Karchmer TB, Giannetta ET, Muto CA, Strain BA, Farr BM. A randomized crossover study of silver-coated urinary catheters in hospitalized patients. Arch Intern Med 2000;160:3294-3298.

20. Thibon P, Le Coutour X, Leroyer R, Fabry J. Randomized multi-centre trial of the effects of a catheter coated with hydrogel and silver salts on the incidence of hospital-acquired urinary tract infections. J Hosp Infect 2000;45:117-124.

21. Bologna RA, Tu LM, Polansky M, Fraimow HD, Gordon DA, Whitmore KE. Hydrogel/silver ion-coated urinary catheter reduces nosocomial urinary tract infection rates in intensive care unit patients: a multicenter study. Urology 1999;54:982-987.

22. Maki DG, Knasinski V, Halvorson K, Tambyah PA. A novel silver-hydrogel-impregnated indwelling urinary catheter reduces CAUTIs: a prospective double-blind trial [abstract]. Infect Control Hosp Epidemiol 1998;19:682(A10).

23. Stark RP, Maki DG. Bacteriuria in the catheterized patient. What quantitative level of bacteriuria is relevant? N Engl J Med 1984;311:560-564.

24. Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled? Ann Intern Med 1996;125:605-613.

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