International Journal of Antimicrobial Agents 24S (2004) S44S48

Catheter-associated urinary tract infections: diagnosis and prophylaxis

Paul A. Tambyah
Division of Infectious Diseases, Department of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore

Abstract Catheter-associated urinary tract infections (CAUTI) are the commonest nosocomial infections worldwide. While they are often asymptomatic and frequently cost less than nosocomial surgical site infections or nosocomial pneumonia, they are major reservoirs of antimicrobial resistant pathogens. Numerous strategies have been devised in an attempt to reduce the incidence of CAUTI but few have proven effective. Novel technologies such as the potential use of antiseptic or antimicrobial coatings on catheters hold promise for possibly reducing these infections in the ght against antimicrobial resistance. 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Keywords: Catheter-associated urinary tract infection; Prevention; Urinary catheterization

1. Introduction Catheter-associated urinary tract infection (CAUTI) is the most common nosocomial infection in hospitals and nursing homes world-wide with more than one million episodes in the United States alone [1,2]. Although most CAUTIs are asymptomatic [3], rarely extend hospitalization and add only US$ 5001000 to the direct costs of acute care hospitalization [4], asymptomatic infections often precipitate unnecessary antimicrobial therapy. Although the costs of catheter-associated urinary tract infections are not as high as for example a deep surgical site infection or a nosocomial pneumonia, CAUTIs are a cause for concern as they are a major reservoir of resistant pathogens [5,6]. Numerous studies have documented a high prevalence of resistant pathogens in CAUTI and the association between nosocomial CAUTI and surgical site infections has been made [7].

croorganism per ml would predictably multiply over time to reach 105 106 microorganisms per ml in the catheterized urinary tract. They showed that 103 microorganisms per ml is a sensitive cut-off for CAUTI. In non-catheterized patients, by convention, 105 organisms per ml of urine is used as a criterion for diagnosis of UTI but for symptomatic women with UTIs, a much lower colony count has been shown to be valid [9]. There is considerable variation in laboratories and clinicians, in reporting and diagnosing CAUTI on the basis of colony counts. However, the underlying principle remains that the normally sterile urinary tract is vulnerable to colonization and subsequent infection by microorganisms once a catheter is in situ.

3. Pyuria Pyuria is widely used as a criterion for diagnosing urinary tract infections in non-catheterized patients. However, in a large prospective study of more than 750 patients [10], pyuria was found to be most useful in predicting CAUTI in patients with UTI due to Gram-negative pathogens while CAUTI caused by large numbers of yeasts and enterococci or staphylococci were less signicantly associated with pyuria. This is thought to be due to less urinary tract inammation elicited by these organisms. Other studies have predominantly been conducted in long-term catheterized patients and have shown variable results in terms of pyuria as a predictor

2. Diagnosis In a study conducted almost 20 years ago, Stark and Maki [8] showed that in the absence of antibiotics, even one mi Presented in part at the Surgical Infections: Prevention and Management Conference held on 2930 May 2003 in Moscow, Russia. Tel.: +65-6779-5555; fax: +65-6779-4112. E-mail address: mdcpat@nus.edu.sg (P.A. Tambyah).

0924-8579/$ see front matter 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/j.ijantimicag.2004.02.008

P.A. Tambyah / International Journal of Antimicrobial Agents 24S (2004) S44S48

S45

for CAUTI [11,12]. Pyuria alone cannot be used as the criteria for obtaining a urine culture in a catheterized patient. It has been argued that if a catheterized patient develops signs of sepsis that cannot be linked to another source, such as nosocomial pneumonia, surgical site infection, or vascular catheter-related bloodstream infection, a urine culture should be obtained even if the patient does not have demonstrable pyuria.

4. Symptoms Symptoms are also not reliable for the diagnosis of CAUTI. Although many guidelines [13,14] make the distinction between symptomatic CAUTI and asymptomatic bacteriuria in the management of CAUTI, we were unable to demonstrate a difference in presence of fever or symptoms related to the urinary tract in catheterized patients with and without CAUTI, in a large prospective study [4]. The catheter can itself be the source of symptoms as was noted in that study in which the proportion of catheterized patients without CAUTI with symptoms was similar to those with CAUTI. Part of the reason for the absence of symptoms of urethral irritation such as dysuria or supra-pubic pain is that the catheter itself prevents contact of inammatory cells in urine and large numbers of microorganisms with the urethral mucosa. The presence of the urinary catheter in situ also allows for decompression of the bladder, thus preventing the development of symptoms related to bladder distension or reux. It is interesting to note that the majority of cases of bloodstream infection [15] and even in one report [16] mortality associated with CAUTI are in patients where there is signicant urinary obstruction. It has also been shown that patients with long-term indwelling catheters rarely have febrile episodes even though they have chronic signicant amounts of bacteria in their urine [17,18]. This changes when obstruction or encrustation occurs as in that setting, decompression of the infected bladder is compromised.

microbes have to travel from the perineum to the bladder. The second pathway for microorganisms to enter the bladder is the intraluminal route. This is from breaks in the closed drainage system that occurs through irrigation of the bladder without proper asepsis. Alternatively, and perhaps more commonly, the collection-bag urine becomes contaminated through healthcare workers not washing hands when going from bag to bag emptying urine or when changing bags. Either way, contaminated urine can ascend from the bag into the catheter when the bag is raised, often during transport of the patient into and out of operating rooms or radiological suites. This allows microorganisms to ow into the bladder. They can also rise by capillary action even when the bag is below the bed. In a large prospective study of more than 1000 patients with indwelling catheters performed to determine the route of entry of microorganisms causing CAUTI, daily urine cultures were done from the drainage bag and the catheter collection port [20]. The assumption was that if the organism ascended into the bladder by the intraluminal route from the bag, it would appear rst in a culture from the bag. On the other hand, if the microorganism came along the surface of the catheter from the perineum, it would be detected in the catheter sample before it was detected in the bag. Overall, two thirds of infections were caused by organisms ascending along the surface of the catheter. This was more marked for staphylococci and enterococci as well as yeasts which are common commensals of the perineum. For Gram-negative organisms which are often water-borne such as Pseudomonas, Enterobacter or Acinetobacter, the intraluminal route from the collection-bag was more important. These organisms can be carried on the hands of healthcare workers and can be readily transmitted to urine bags. Once they enter the bag, they multiply and can occasionally cause UTIs by either capillary action or by inadvertent transfer into the bladder during transport. Outbreaks of these organisms in particular, Serratia, have been well reported and associated with a variety of urinary collection devices [21].

5. Pathogenesis 6. Risk factors The entry of a urinary catheter bypasses the normal host defences at the meatus and allows the entry of pathogens into the bladder. The presence of a foreign body also allows for the formation of a biolm, which is a conduit for pathogens to multiply and cause infection. It has been postulated that there are two main routes for CAUTI. Firstly, the extraluminal route: this could be either early at the time of catheter insertion due to inadequate antisepsis or contamination, or late due to colonisation of the meatus and the ascent of microorganisms from the perineum along the surface of the catheter. Early studies by Garibaldi et al. [19] have shown that meatal colonisation is associated with CAUTI. Women are also much more likely to have CAUTI due to their shorter urethras and thus the shorter distance At least ve prospective studies [2226] have conducted multivariate analysis of the risk factors associated with CAUTI with daily urine cultures to detect all CAUTIs in large numbers of patients. These studies were found to have remarkably similar results. The most important risk factors have been prolonged catheterization and being female. Other risk factors identied have included catheterization outside the sterile environment of the operating room, being on a urology service which might simply mean having a urinary tract abnormality, other infections, diabetes, malnutrition and renal failure. Interestingly, most of the infection control interventions were found to have a minimal impact on the incidence of CAUTI with one exceptionif

S46

P.A. Tambyah / International Journal of Antimicrobial Agents 24S (2004) S44S48

the drainage tube was allowed to be above the level of the patient; that was a major risk factor for infection. Antibiotics were in general protective, but the infections (when they occurred) tended to be caused by antibiotic-resistant organisms.

silver-coated catheters including silver oxide catheters and silver alloy catheters. Silver oxide catheters were found to have no benet in prevention of CAUTI in two large studies [42,43] while a meta-analysis of silver alloy coated catheters suggests that they are benecial [44].

7. Prevention The best way of preventing a CAUTI is to remove the catheter or to avoid its use. All studies have shown the duration of catheterization as a signicant risk factor for nosocomial CAUTI [2225]. A recent study by Saint et al. [27] showed that a number of physicians at various levels are unaware that their patients are catheterized. Catheters have been described as a one-point restraint for hospitalized patients [28], and in a classic editorial nearly half a century ago, Beeson made the case against the catheter [29]. One problem is that there are few viable alternatives to a urinary catheter for patients who are incontinent or have urinary obstruction. The use of diapers also has its own problems in terms of skin damage and pressure sores. They are also very expensive and demoralizing for the patient. Condom catheters have been shown in at least one nursing home study to reduce the risk of CAUTI but they are obviously limited to men without obstruction [30]. Although supra-pubic catheters are associated with a decreased rate of CAUTI [31], there are some data suggesting that there are problems. Many innovations have been tried to reduce CAUTI. These have been targeted at both the extraluminal as well as intraluminal routes of CAUTI. These have included the use of antiinfective lubricants at the time of insertion [3234], sealed catheter-tube junctions to prevent breaks in closed drainage [3537], antireux valves or antiinfective irrigation of the bladder or instillation of antiseptics in the collection-bag [3840]. In well-designed randomized trials over the last 20 or so years, all of these have failed to show signicant benets. In the last few years, renewed interest has arisen in the use of antiinfective catheter material. These have been used successfully in central venous catheters and have been studied for urinary catheters as well. The results have been varied but promising. A novel silver hydrogel catheter was recently found to be mainly benecial for infections arising by the extraluminal route along the catheter surface [41].

9. Antibiotic coated catheters Antibiotic coated catheters using a combination of rifampicin and minocycline [45] have been used and were found to be effective in preventing nosocomial intravenous catheter related infections as well [46]. The rifampicin-minocycline catheter was most effective in preventing CAUTI caused by Gram-positive rather than Gram-negative bacteria thus limiting its practical efcacy. The concern has been in the development of antibiotic resistance. In many parts of the world, where Mycobacterium tuberculosis is endemic, the widespread use of rifampicin coated catheters would be a cause for concern, if this was found to be associated with increased rates of drug-resistant tuberculosis.

10. Novel technologies Other technologies that appear promising on the horizon include the use of urethral stents [47]. Even further on the horizon perhaps are technologies, which translate bench research into cell-cell communications which would inhibit the formation of the biolm in the rst place. Quorum sensing is an area of intense research interest. A quorum sensing inhibitor has been shown in vivo to be effective in preventing the development of a biolm by Staphylococcus epidermidis [48] and this could possibly be translated into a novel device for the prevention of CAUTI.

11. Conclusion There are clearly many challenges that face researchers and clinicians working in the eld of CAUTI. Foremost among these must be the prevention of these infections. Effective interventions to prevent CAUTI will doubtless help to reduce the reservoir of resistant pathogens in the intensive care units, wards and long-term care facilities. This will be a critical step in the battle against antibiotic resistance.

8. Silver-coated catheters References Silver is a well-known antiseptic with a long history, as an antiseptic rather than an antibiotic and the risk of generating antibiotic resistance would be expected to be low. Argyrism is a potential concern that has limited the use of silver on the internal coating of catheters and possibly limited its efcacy. There are a number of studies that have evaluated
[1] Burke JP, Riley DK. Nosocomial urinary tract infection. In: Mayhall CG, editor. Hospital Epidemiology and Infection Control. Baltimore, MD: Williams and Wilkins; 1996. p. 13953. [2] Kunin CM. Care of the urinary catheter. In: Urinary Tract Infections: Detection, Prevention and Management. 5th ed. Baltimore, MD: Williams & Wilkins; 1997. p. 22779.

P.A. Tambyah / International Journal of Antimicrobial Agents 24S (2004) S44S48 [3] Tambyah PA, Maki DG. Catheter-associated urinary tract infection is rarely symptomatic: a prospective study of 1497 catheterized patients. Arch Intern Med 2000;160:67882. [4] Tambyah PA, Knasinski V, Maki DG. The direct economic costs of nosocomial catheter-associated urinary tract infection in the era of managed care. Infect Control Hosp Epidemiol 2002;23:27 31. [5] Jarlier V, Fosse T, Philippon A. Antibiotic susceptibility in aerobic gram-negative bacilli isolated in intensive care units in 39 French teaching hospitals. Intens Care Med 1996;22:105765. [6] Bjork DT, Pelletier LL, Tight RR. Urinary tract infections with antibiotic resistant organisms in catheterized nursing home patients. Infect Control 1984;5:1736. [7] Krieger JN, Kaiser DL, Wenzel RP. Nosocomial urinary tract infections cause wound infections postoperatively in surgical patients. Surg Gynecol Obstet 1983;156:3138. [8] Stark RP, Maki DG. Bacteriuria in the catheterized patient. What quantitative level of bacteriuria is relevant? N Engl J Med 1984;311:5604. [9] Stamm WE, Hooton TM. Management of urinary tract infections in adults. N Engl J Med 1993;329:132834. [10] Tambyah PA, Maki DG. The relationship between pyuria and infection in patients with indwelling urinary catheters: a prospective study of 761 patients. Arch Intern Med 2000;160:6737. [11] Peterson JR, Roth EJ. Fever bacteriuria and pyuria in spinal cord injured patients with indwelling urethral catheters. Arch Phys Med Rehabil 1989;70:83941. [12] Musher DM, Thorsteinsson SB, Airola VM. Quantitative urinalysis: diagnosing urinary tract infection in men. JAMA 1976;236:2069 72. [13] OGrady NP, Barie PS, Bartlett J, et al. Practice parameters for evaluating new fever in critically ill adult patients. Crit Care Med 1998;26:392408. [14] National Institute on Disability and Rehabilitation Research. The prevention and management of urinary tract infections among people with spinal cord injuries: National Institute on Disability and Rehabilitation Research Consensus Statement. J Am Paraplegia Soc 1992;15:194204. [15] Bryan CS, Reynolds KL. Hospital acquired bacteremic urinary tract infection: epidemiology and outcome. J Urol 1984;132:4948. [16] Quintiliani R, Klimek J, Cunha BA, Maderazo EG. Bacteraemia after manipulation of the urinary tract: the importance of preexisting urinary tract disease and compromised host defences. Postgrad Med J 1978;54:66871. [17] Kunin CM, Chin QF, Chambers S. Morbidity and mortality associated with indwelling urinary catheters in elderly patients in a nursing home: confounding due to the presence of associated diseases. J Am Geriatr Soc 1987;35:10016. [18] Warren JW, Damron D, Tenney JH, Hoopes JM, Deforge B, Muncie HL. A prospective microbiologic study of bacteriuria in patients with chronic indwelling urinary catheters. J Infect Dis 1987;6:11518. [19] Garibaldi RA, Burke JP, Britt MR, Miller MA, Smith CB. Metal colonization and catheter-associated bacteriuria. N Engl J Med 1980;30:33168. [20] Tambyah PA, Halvorson K, Maki DG. A prospective study of the pathogenesis of catheter-associated urinary tract infection. Mayo Clin Proc 1999;74:1316. [21] Maki DG, Hennekens C, Bennet J. Prevention of catheter-associated urinary tract infection. JAMA 1972;221:12701. [22] Garibaldi RA, Burke JP, Dickman ML, Smith CB. Factors predisposing to bacteriuria during indwelling urethral catheterization. N Engl J Med 1974;291:2159. [23] Platt R, Polk BF, Murdock B, Rosner B. Risk factors for nosocomial urinary tract infection. Am J Epidemiol 1986;124:97785. [24] Shapiro M, Simchen E, Izraeli S, Sacks TO. A multivariate analysis of risk factors for acquiring bacteriuria in patients with indwelling

S47

[25]

[26]

[27]

[28] [29] [30] [31]

[32] [33]

[34]

[35]

[36] [37]

[38]

[39]

[40]

[41] [42]

[43]

[44]

[45]

urinary catheters for longer than 24 hours. Infect Control 1984;5:525 32. Johnson JR, Roberts PL, Olsen RJ, Moyer KA, Stamm WE. Prevention of catheter-associated urinary tract infection with a silver oxide-coated urinary catheter: clinical and microbiologic correlates. J Infect Dis 1990;162:114550. Riley DK, Classen DC, Stevens LE, Burke JP. A large randomized clinical trial of a silver impregnated urinary catheter: lack of efcacy and staphylococcal superinfection. Am J Med 1995;98:349 56. Saint S, Wiese J, Amory JK. Are physicians aware of which of their patients have indwelling urinary catheters? Am J Med 2000;109:476 80. Saint S, Lipsky BA, Goold SD, et al. Indwelling urinary catheters: a one-point restraint? Ann Intern Med 2002;137:1257. Beeson PB. The case against the catheter. Am J Med 1958;24:13. Warren JW. Uretheral catheters. Infect Control Hosp Epidemiol 1996;17:2124. Shapiro J, Hoffmann J, Jersky J. A comparison of suprapubic and transurethral drainage for postoperative urinary retention in general surgical patients. Acta Chirurgica Scandinavia 1982;148:3237. Butler HK, Kunin CM. Evaluation of polymyxin catheter lubricant and impregnated catheters. J Urol 1968;100:5606. Kunin CM, Finkelberg Z. Evaluation of an intraurethral lubricating catheter in prevention of catheter-induced urinary tract infections. J Urol 1971;106:92830. Schiotz HA. Antiseptic catheter gel and urinary tract infection after short-term postoperative catheterization in women. Arch Gynecol Obstet 1996;258:97100. Huth TS, Burke JP, Larsen RA. Clinical trial of junction seals for the prevention of urinary catheter-associated bacteriuria. Arch Intern Med 1992;152:80712. Platt R, Polk BF, Murdock B, Rosner B. Reduction of mortality associated with nosocomial urinary tract infection. Lancet 1983;i:8937. Classen DC, Larsen RA, Burke JP. Stevens LE. Prevention of catheter-associated bacteriuria: clinical trial of methods to block three known pathways of infection. Am J Infect Control 1991;19:136 42. Warren JW, Platt R, Thomas RJ, Rosner B, Kass EH. Antibiotic irrigation and catheter associated urinary tract infections. N Engl J Med 1978;299:5703. Gillespie WA, Simpson RA, Jones JE, Nashef L, Teasdale C, Speller DCE. Does the addition of disinfectant to urine drainage bags prevent infection in catheterized patients. Lancet 1983;i:10379. Thomson RL, Haley CE, Searcy MA, et al. Catheter-associated bacteriuria: failure to reduce attack rates using periodic instillations of a disinfectant into urinary drainage systems. JAMA 1984;251:747 51. Maki DG, Tambyah PA. Engineering out the risk of infection with urinary catheters. Emerg Infect Dis 2001;7:3427. Johnson JR, Roberts PL, Olsen RJ, Moyer KA, Stamm WE. Prevention of catheter-associated urinary tract infection with a silver oxide-coated urinary catheter: clinical and microbiologic correlates. J Infect Dis 1990;162:114550. Riley DK, Classen DC, Stevens LE, Burke JP. A large randomized clinical trial of a silver-impregnated urinary catheter: lack of efcacy and staphylococcal superinfection. Am J Med 1995;98:349 56. Saint S, Elmore JG, Sullivan SD, Emerson SS, Koepsell TD. The efcacy of silver alloy-coated urinary catheters in preventing urinary tract infection: a meta-analysis. Am J Med 1998;105:234 6. Darouiche RO, Smith A, Hanna H, Dhabuwala CB, Steiner MS, Babian RJ, et al. Efcacy of antimicrobial-impregnated bladder catheters in reducing catheter-associated bacteriuria: a prospective randomized multi-center trial. Urology 1999;4:97681.

S48

P.A. Tambyah / International Journal of Antimicrobial Agents 24S (2004) S44S48 [47] Nissenkorn I. The intraurethral catheter-three years of experience. Eur Urol 1993;24:2730. [48] Balaban N, Giacometti A, Cirioni O, et al. Use of the quorum-sensing inhibitor RNA. IIIinhibiting peptide to prevent biolm formation in vivo by drug-resistant Staphylococcus epidermidis. J Infect Dis 2003;187:62530.

[46] Raad I, Darouiche RO, Dupuis J, et al. Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. A randomized double-blind trial. The Texas Medical Center Catheter Study Group. Ann Intern Med 1997;127:267 74.