Efficacy of a Silicone Urinary Catheter Impregnated with Chlorhexidine and Triclosan Against Colonization With Proteus mirabilis and Other Uropathogens
We sought to develop an infection‐resistant urinary catheter. We evaluated 3 types of catheters for their efficacy against uropathogens in an in vitro model of the urinary tract. The catheter impregnated with chlorhexidine and triclosan suppressed the growth of uropathogens, including Proteus mirabilis, for 20‐30 days or longer.
Received April 24, 2006; accepted July 13, 2006; electronically published March 22, 2007.
Patients who undergo long‐term bladder catheterization show polymicrobial infection and experience encrustation of their catheters, mostly related to infection with urease‐producing bacteria,1‐3 including Proteus mirabilis.4 Infection with Proteus species is frequently associated with catheter obstruction by struvite and apatite stones,4 leading to chronic pyelonephritis and renal dysfunction.5,6 The preventive measures existing today, including the use of antimicrobial‐impregnated urinary catheters and bladder irrigation with an antimicrobial solution,7‐9 have not been of significant benefit for patients who undergo long‐term catheterization.
In a previous study,10 we reported that a Foley catheter impregnated with chlorhexidine, silver sulfadiazine, and triclosan was effective in prevention of catheter colonization with certain uropathogens for more than 15 days. However, the efficacy of that catheter against other important pathogens, including P. mirabilis, was short‐lived (unpublished data).
The objective of the present study was to develop an antimicrobial catheter with prolonged activity against most uropathogens, particularly P. mirabilis. In this study, a silicone catheter impregnated with a combination of chlorhexidine and triclosan by a novel method was evaluated for its efficacy in prevention of colonization with various pathogens, by use of an in vitro model of the urinary tract that was developed in our laboratory, as described elsewhere.10 Furthermore, this catheter's efficacy was compared with that of the catheter impregnated with chlorhexidine, silver sulfadiazine, and triclosan and the nitrofurazone‐coated catheter.
Methods
Bacterial strains. The organisms selected for this study included clinical isolates of vancomycin‐resistant Enterococcus faecium, methicillin‐resistant Staphylococcus aureus (MRSA), Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, P. mirabilis, Enterococcus faecalis, and Candida albicans, which were obtained from Columbia Presbyterian Hospital (New York).
Catheters. Uncoated silicone Foley catheters and nitrofurazone‐coated catheters were purchased from Rochester Medical. Uncoated catheters were impregnated with chlorhexidine and triclosan by use of a proprietary 2‐step method. For the catheters impregnated with chlorhexidine, triclosan, and silver sulfadiazine, the chlorhexidine and triclosan were impregnated using a 1‐step method, as used in our previous study.10 The same silicone catheters without any antiseptic were used as the control catheters.
Antiseptics and growth media. Chlorhexidine and triclosan were obtained from George Uhe and Ciba Specialty Chemicals, respectively. The special medium used for the agar tract of the in vitro model contained 4% trypticase soy agar (Fisher Scientific) with 1% Bacto‐Agar (Difco Laboratories).
Efficacy tests in the in vitro model of the urinary tract. Catheters impregnated with chlorhexidine and triclosan; catheters impregnated with chlorhexidine, silver sulfadiazine, and triclosan; catheters coated with nitrofurazone; and unimpregnated control catheters (6 cm in length) were tested in the in vitro model of the urinary tract.10 A total of 6 catheter segments were evaluated for each pathogen. Specimens from the bladder model were cultured on trypticase soy agar each day to check for the presence of bacteria. The day on which there was a positive result of bladder‐model culture was considered the end point. The testing was discontinued after 30 days of negative results of bladder‐model culture.
Results
The catheter impregnated with chlorhexidine and triclosan prevented colonization with K. pneumoniae, E. aerogenes, P. mirabilis, MRSA, vancomycin‐resistant E. faecium, E. faecalis, E. coli, and C. albicans for 20‐30 days or longer, compared with 4‐10 days for the catheters impregnated with chlorhexidine, silver sulfadiazine, and triclosan and for the nitrofurazone‐coated catheters. Control catheters were colonized in 1‐2 days (Figures 1 and 2).
Figure 1. Comparison of efficacy of catheters impregnated with chlorhexidine, silver sulfadiazine, and triclosan (CXST); catheters impregnated with chlorhexidine and triclosan (CXT+); catheters coated with nitrofurazone (NF); and control catheters against various uropathogens, including Klebsiella pneumoniae, Enterobacter aerogenes, and Proteus mirabilis, in the in vitro model of the urinary tract.
Figure 2. Efficacy of the catheter impregnated with chlorhexidine and triclosan (CXT+) and a control catheter against various uropathogens, including Enterococcus faecalis, methicillin‐resistant Staphylococcus aureus (MRSA), vancomycin‐resistant Enterococcus faecium (VREF), Escherichia coli, and Candida albicans, in the in vitro model of the urinary tract.
Discussion
Most of the antimicrobial catheters evaluated to date have not shown broad ‐spectrum activity and were ineffective over the long term.7,11‐13 In recent studies, inflation of the retention balloons with triclosan prevented the encrustation of catheters for 7 days in laboratory models of the bladder that were infected with P. mirabilis.14,15
We had previously found that a catheter impregnated with chlorhexidine, silver sulfadiazine, and triclosan was effective in the prevention of colonization with S. aureus, Staphylococcus epidermidis, E. coli, and C. albicans for 15‐24 days but had limited efficacy against K. pneumoniae, E. aerogenes, P. mirabilis (data not published), and E. faecalis.10 It appears that the rate of release of chlorhexidine and triclosan from the catheter impregnated with chlorhexidine, silver sulfadiazine, and triclosan is inadequate for prevention of colonization of the catheter with these bacteria. The new catheter used in the present study, which was impregnated with chlorhexidine and triclosan, was developed using a novel method, which permits prolonged release of a synergistic combination of these 2 agents in effective amounts.
On the basis of the results of animal studies,16,17 the new catheter, which has initial levels of 607 μg/cm of chlorhexidine and 415 μg/cm of triclosan and average release rates of 14.5 μg/day of chlorhexidine and 3.7 μg/day of triclosan, might not cause mucosal irritation or toxicity. The catheter exhibited prolonged efficacy against the pathogens tested and had superior activity compared with that of the other catheters tested (Figures 1 and 2). These results indicate that the catheter impregnated with chlorhexidine and triclosan may reduce urinary tract infections caused by a broad spectrum of uropathogens, including P. mirabilis, MRSA, and vancomycin‐resistant E. faecium, which are associated with long‐term catheterization.
The new catheter was effective for only 10 days against Pseudomonas aeruginosa (data not shown), which may be because of the higher minimum inhibitory concentration of chlorhexidine and triclosan for this organism, compared with that of other pathogens.18,19 We are continuing our research on improving the efficacy of the catheter against P. aeruginosa. Furthermore, a study by Tambe et al.20 indicated that the use of catheters impregnated with antiseptics such as chlorhexidine and triclosan may reduce the risk of emergence of drug‐resistant organisms.
In conclusion, silicone catheters impregnated with a synergistic combination of chlorhexidine and triclosan by use of a novel impregnation method show prolonged efficacy against colonization with important uropathogens, including drug‐resistant bacteria and P. mirabilis. This catheter may suppress the growth of pathogens associated with long‐term catheterization, with a reduced risk of emergence of resistant organisms.
Acknowledgments
Potential conflicts of interest. All authors report no conflicts of interest relevant to this article.
References
- 1. Bruce AW, Sira SS, Clark AF, Awad SA. The problem of catheter encrustation. Can Med Assoc J 1974; 111:238‐241.
- 2. Hukins DWL, Hickey DS, Kennedy AP. Catheter encrustation by struvite. Br J Urol 1983; 55:304‐305.
- 3. Getliffe KA, Mulhall AB. The encrustation of indwelling catheters. Br J Urol 1991; 67:337‐341.
- 4. Kunin CM. Blockage of urinary catheters: role of microorganisms and constituents of the urine on formation of encrustations. J Clin Epidemiol 1989; 42:835‐842.
- 5. Warren JW. Catheter associated urinary tract infections. Int J Antimicrob Agents 2001; 17:299‐303.
- 6. Ronald A. The etiology of urinary tract infection: traditional and emerging pathogens. Am J Med 2002; 113(suppl 1A):14S‐19S.
- 7. 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.
- 8. Lee SJ, Kim SW, Cho YH, et al. A comparative multi‐centre study on the incidence of catheter‐associated urinary tract infection between nitrofurazone‐coated and silicone catheters. Int J Antimicrob Agents 2004; 24(suppl 1):S65‐S69.
- 9. Pearman JW. The value of kanamycin‐colistin bladder instillations in reducing bacteriuria during intermittent catheterization of patients with acute spinal cord injury. Br J Urol 1979; 51:367‐374.
- 10. Gaonkar TA, Sampath LA, Modak SM. Evaluation of the antimicrobial efficacy of urinary catheters impregnated with antiseptics in an in vitro urinary tract model. Infect Control Hosp Epidemiol 2003; 24:506‐513.
- 11. Darouiche RO, Smith JA, Dhabuwala CB, et al. Efficacy of antimicrobial‐impregnated bladder catheters in reducing catheter‐associated bacteriuria: a prospective, randomized, multi‐centre clinical trial. Urology 1999; 54:976‐981.
- 12. Maki DG, Tambyah PA. Engineering out the risk of infection with urinary catheters. Emerg Infect Dis 2001; 7:1‐6.
- 13. Schaeffer AJ, Story KO, Johnson SM. Effect of silver oxide/trichloroisocyanuric acid antimicrobial urinary drainage system on catheter associated bacteriuria. J Urol 1988; 139:69‐73.
- 14. Jones GLI, Russell AD, Caliskan Z, Stickler DJ. A strategy for the control of catheter blockage by crystalline Proteus mirabilis biofilm using the antibacterial agent triclosan. Eur Urol 2005; 48:838‐845.
- 15. Jones GLI, Muller CT, O’Reilly M, Stickler DJ. Effect of triclosan on the development of bacterial biofilms by urinary tract pathogens on urinary catheters. J Antimicrob Chemother 2006; 57:266‐272.
- 16. Richards CL, Hoffman KC, Bernhard JM, Winslow SD, Norman JC, Whalen RL. Development and characterization of an infection inhibiting urinary catheter. ASAIO J 2003; 49:449‐453.
- 17. Kim CY, Kumar A, Sampath L, Sokol DVM, Modak SM. Evaluation of an antimicrobial impregnated continuous ambulatory peritoneal dialysis catheter for infection control in rats. Am J Kidney Dis 2002; 39:165‐173.
- 18. do Amorim CV, Aun CE, Mayer MP. Susceptibility of some oral microorganisms to chlorhexidine and paramonochlorophenol. Pesqui Odontol Bras 2004; 18:242‐246.
- 19. Jones GL, Muller CT, O’Reilly M, Stickler DJ. Effect of triclosan on the development of bacterial biofilms by urinary tract pathogens on urinary catheters. J Antimicrob Chemother 2006; 57:266‐272.
- 20. Tambe SM, Sampath L, Modak SM. In vitro evaluation of the risk of developing bacterial resistance to antiseptics and antibiotics used in medical devices. J Antimicrob Chemother 2001; 47:589‐598.