Catheter-associated urinary tract infections

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1 International Journal of Antimicrobial Agents 17 (2001) Catheter-associated urinary tract infections John W. Warren * Di ision of Infectious Diseases, Uni ersity of Maryland School of Medicine, 10 S. Pine Street, Room 9-00, Baltimore, MD 21201, USA Abstract Nosocomial urinary tract infection (UTI) is the most common infection acquired in both hospitals and nursing homes and is usually associated with catheterization. This infection would be even more common but for the use of the closed catheter system. Most modifications have not improved on the closed catheter itself. Even with meticulous care, this system will not prevent bacteriuria. After bacteriuria develops, the ability to limit its complications is minimal. Once a catheter is put in place, the clinician must keep two concepts in mind: keep the catheter system closed in order to postpone the onset of bacteriuria, and remove the catheter as soon as possible. If the catheter can be removed before bacteriuria develops, postponement becomes prevention Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved. Keywords: Nosocomial UTI; Catheter-associated UTI; Prevention of catheter-associated UTI; Bacteremia 1. Introduction The urethral catheter is one of the most venerable of medical devices, having been used for urine retention on an intermittent or indwelling basis for centuries. In the 1920s, Foley introduced a catheter which could be held in place with an intra-bladder balloon. In the first several decades of use, Foley catheters were attached to collecting tubes which drained into buckets placed on the floor beside the bed, the so-called open-catheter system. Bacteriuria occurred by the end of 4 days. The 1950s saw the progressive development of closed catheter systems. Plastic collection bags fused to the distal end of the tubes began to be used in the 1960s. This arrangement allows drainage through a tube into a receptacle so that the urine is always contained within a lumen protected from the contaminated environment. The onset of bacteriuria is now more than 30 days in closed catheter systems. Although no well-designed controlled trials comparing open with closed catheters have been performed, reports have been sufficiently positive so that the closed system has become the standard for patients requiring indwelling urethral catheters. * Fax: Pathogenesis Insertion of a catheter may carry urethral organisms into the bladder. The catheter may be disconnected from the collection tube and bacteriuria has been associated with such interruptions. The drainage tube of the collection bag must be opened periodically to drain accumulated urine. If the lumen of the drainage tube is contaminated with bacteria, organisms may enter the drainage bag and ascend the collection tube and catheter. Even with meticulous attention to maintenance of the closed system, the space between the external catheter and the urethral mucosa offers opportunity for bacterial entry directly into the bladder and this is the most common route of entry for bacteria [1]. In marked contrast to the non-catheterized urinary tract where small numbers of organisms introduced in the bladder are eliminated efficiently, most bacterial strains that enter the catheterized urinary tract are able to multiply to high concentrations within a day [2]. Biofilm, which covers and secures bacteria against a catheter or mucosal surface, has been demonstrated on drainage bags, catheters, and the uroepithelium. Organisms contained within the biofilm appear to be well-protected from the mechanical flow of urine, host defenses, and even antibiotics. The biofilm may allow the contained sessile organisms to establish a microenvironment from which some may move into the urine; these /01/$ - $ Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved. PII: S (00)

2 300 J.W. Warren / International Journal of Antimicrobial Agents 17 (2001) planktonic microbes are those that are voided and enumerated as bacteriuria by the diagnostic microbiology laboratory. Additionally, the catheter may mechanically damage urinary epithelium and the glycosaminoglycan layer. As a foreign body, the catheter may disrupt adequate anti-bacterial polymorphonuclear leukocyte function. Finally, catheter drainage is often imperfect and volumes of urine may remain in the bladder, thus allowing some stability to the residence of bacteria. The duration of catheterization is the most important risk factor for the development of catheter-associated bacteriuria [3] and is a result of the indications for urethral catheterization: 1. Surgery, 2. Urine output measurement, 3. Urine retention, and 4. Urinary incontinence. Once a urethral catheter is in place, in patients in a hospital or a nursing home, the daily increase in prevalence of bacteriuria is 3 10% [4]. The great majority of catheterized patients will be bacteriuric by the end of 30 days, a convenient dividing line between short-term and long-term catheterization Short-term catheterization Between 15 and 25% of patients in general hospitals may have a catheter in place sometime during their stay. Most are in place for only a short time, up to one-third for less than a day; both the mean and median durations are between 2 and 4 days. In shortterm catheterization, common bacteriuric species such as Escherichia coli are isolated. Other common organisms are Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus epidermidis, enterococci, and Candida species. Most bacteriuria in short-term catheterization is of single organisms. Most episodes of short-term catheter-associated bacteriuria are asymptomatic [5]. Less than 5% of catheterassociated bacteriuric patients will be identified with bacteremia, but because of the large number of catheterized patients, these bacteremias comprise up to 15% of nosocomial blood stream infections [6]. The contribution of catheter-associated UTI to mortality is unclear. At autopsy, patients with catheter-associated bacteriuria dying in a hospital may have acute pyelonephritis, urinary stones, or perinephric abscesses. However, in prospective or case-controlled studies, catheter-associated urinary tract infections (UTIs) are often not found to be associated with excess mortality. One study, however, has suggested an increased risk of death associated with catheter-associated bacteriuria [7]. Minimal estimates are that catheter-associated bacteriuria add 1 day of hospitalization for the bacteriuric patient. The significance of this is magnified by the large number of catheters in use and the high incidence of infection in the US. Catheter-associated bacteriuria is estimated to cause additional hospital days per year. Nosocomial UTIs directly cause almost 1000 deaths and contribute to an additional 6500 deaths per year in the US [8] Long-term catheterization Although the magnitude of long-term urethral catheter use has not been directly measured, several studies suggest that at any given time, more than patients in American nursing homes have urethral catheters in place [9]. Many of these patients have been catheterized for months or years. The two most frequent indications are urinary incontinence and bladder outlet obstruction. Even with excellent care, all patients will become bacteriuric if catheterized long enough. This universal prevalence of bacteriuria is a function of two related phenomena. The first is the incidence of new episodes of bacteriuria similar to that seen in short-term catheterized patients, although caused by a wide variety of gram-negative and gram-positive bacterial species [10]. The second is the ability of some of these strains to persist for weeks in the catheterized urinary tract. At least two types of bacteria inhabit the long-term catheterized urinary tract. The first comprises common uropathogens such as E. coli which have adhered to uroepithelium just as they would in the noncatheterized urinary tract. The second is of other organisms such as Pro idencia stuartii which are rarely found outside the catheterized urinary tract and may use the catheter itself as a niche. These phenomena result in polymicrobial bacteriuria in up to 95% of urine specimens from long-term catheterized patients. Such specimens commonly have two to four bacterial species, each at concentrations of 10 5 cfu/ml or more; some may even have up to six to eight species at similar concentrations [10]. Complications of long-term catheter-associated bacteriuria fall into two categories. The first includes symptomatic UTIs such as seen with short-term catheterization, i.e. fever, bacteremia, and acute pyelonephritis [11 14]. Some of these episodes may end in death. The second group is more often associated with long-term catheterization: obstruction, urinary tract stones [15,16], local periurinary infections, chronic pyelonephritis [17,18] and with prolonged use, bladder cancer [19]. Although two-thirds of febrile episodes in aged longterm catheterized patients may arise from the urinary tract, the incidence is low, about one episode per 100 days of catheterization. Most women presents with low-grade fever, lasting for 1 day or less, and resolve without antibiotic therapy or catheter change [11].

3 J.W. Warren / International Journal of Antimicrobial Agents 17 (2001) UTIs are the most common source of bacteremias in nursing homes [12] and the indwelling urethral catheter is the leading risk factor for bacteremia. Patients with catheters in place are about 60 times more likely to be bacteremic over a 1-year period than patients without catheters [13]. Although E. coli is significantly more likely than other bacteriuric organisms to cause bacteremia, others, even non-uropathogens such as P. stuartii or Morganella morganii, can do so as well. Acute pyelonephritis is undoubtedly the source of many of these febrile episodes. Moreover, autopsies have revealed acute pyelonephritis in more than one third of patients dying with long-term catheters in place [14]. Bacteriuria caused by P. mirabilis is associated with catheter obstruction, probably because of its potent urease, which hydrolyses urea to ammonia, increasing urine ph and causing crystallization of struvite and apatite in the catheter lumen [15,16]. A similar process may occur in the urinary tract itself resulting in infection stones, a common problem in long-term catheterized patients. Such stones in the bladder, often crusting around the catheter balloon and tip, are relatively benign. However, renal stones may be more serious and are associated with chronic pyelonephritis and renal dysfunction [17,18]. 3. Prevention 3.1. Pre ention of catheterization The last several decades have seen major advances in understanding complications of catheterization which prompted attention to the use of alternatives such as patient training, biofeedback, medications, surgery, and using special clothes and bed-clothes. Additionally, several devices have been explored as options to the urethral catheter. For men with urinary incontinence, condoms applied about the penis that empty through a collection tube into a drainage bag have been widely used. Although these avoid problems of having a tube in the urinary tract, urine within these condom catheters may develop high concentrations of organisms, the urethra and skin may be colonized with uropathogens, and bladder bacteriuria may develop [20]. Although no properly-designed controlled trials have been performed, parallel studies of condom catheters and urethral catheters in the same institution suggest a substantially lower incidence of bacteriuria with condom catheters [21,22]. Following its re-introduction in the 1940s, intermittent catheterization by the 1970s had become the standard of care for spinal injured patients. Insertion of a catheter every 3 6 h by caregivers or the patient, drainage of urine, and immediate removal of the catheter provide periodic bladder emptying. The incidence of bacteriuria is about 1 3% per catheterization [23]. A randomized study comparing clean versus sterile catheters showed no difference in symptomatic UTI but did show that clean catheterization was associated with reduced costs [24]. Oral antibiotics and methenamine compounds as well as instillations of povidone iodine and chlorhexidine preparations have been used to postpone bacteriuria for short periods in intermittently catheterized patients; whether such practices would be beneficial over months and years has not been shown. Bacteriuria is usually asymptomatic and, although no well-designed comparisons have been performed, intermittent catheterization may be an improvement over indwelling catheterization in regard to local periurethral infections, febrile episodes, bacteremia, bladder and renal stones, and deterioration of renal function. Suprapubic catheterization has been increasingly used in several types of surgery. Studies have randomly assigned patients to suprapubic or urethral catheterization and some have shown significant benefits of suprapubic catheterization in terms of lowering the incidences of bacteriuria, urethral strictures, or pain [25] Pre ention of bacteriuria Once a urethral catheter is in place, only two principles are universally recommended for prevention of bacteriuria: keep the closed catheter system closed and remove the catheter as soon as possible. Urine specimens should be obtained without opening the cathetercollection tube junction. The only point at which the system must be opened is the bag drainage tube and personnel must avoid touching the end of the drainage tube to possibly contaminated containers. If the catheter can be removed before bacteriuria develops, postponement becomes prevention. More than a third of days late in catheterization courses may be unnecessary [5]. A reasonable management tool would be a daily review of the necessity to continue catheterization in any given patient. Although many logical modifications have been attempted, most have not markedly improved upon the ability of the closed system to postpone bacteriuria. Irrigation of the catheter and bladder with antibacterial solutions has not curtailed bacteriuria. Additionally, antimicrobials in the collection bag have generally been ineffective. Given that the potential space between the urethra and the external catheter surface is probably the most common route of entry for organisms, numerous investigators have attempted to block this pathway by applying topical antibacterial agents. However, studies have shown little if any, postponement of bacteriuria with such techniques. Indeed, several studies revealed that patients receiving such agents actually tended to have an increased incidence of bacteriuria, a

4 302 J.W. Warren / International Journal of Antimicrobial Agents 17 (2001) finding attributed to physical manipulation of the urethra allowing easier ingress of urethral and periurethral bacteria. Another modification has been to manipulate the composition of the catheter material [26,27]. Most studies of using systemic antibiotics, retrospective or prospective, have demonstrated effectiveness in initially diminishing the incidence of bacteriuria in catheterized patients. In hospitals, up to 80% of catheterized patients are administered antibiotics during but not usually because of catheterization. Nevertheless, those studies which followed patients long enough, revealed that antibiotics were effective for the first several days before resistant organisms began to appear in the urine. Most authorities feel that the use of antibiotics to postpone bacteriuria is not indicated because of side effects, cost, and emergence of resistant bacteria in the patient and in the medical unit. There may be exceptions to this generalization. For instance, patients at high risk for complications of catheter-associated bacteriuria, e.g. renal transplant and granulocytopenic patients, might benefit from antibiotic use during short-term catheterization Pre ention of complications of bacteriuria Treatment with antibiotics of asymptomatic bacteriuria in catheterized patients may seem a logical preventive measure for the complications of fever, urinary symptoms, acute pyelonephritis, and bacteremia. However, the data available suggest that this approach is not particularly useful. Garibaldi et al. noted that in hospitalized patients, symptomatic catheter-associated UTIs tended to occur on the first day of bacteriuria [28]. These patients would be precluded from effective prevention with antibiotics. Furthermore, even if antibiotics prescribed for asymptomatic bacteriuria were 100% effective in preventing the delayed symptomatic UTIs, for each one prevented, 250 urine cultures would be required to identify the asymptomatic bacteriuria s precipitating treatment. In long-term catheterized patients, the hypothesis that antibiotic treatment of catheter-associated bacteriuria will prevent symptomatic UTIs has been tested in a prospective trial. In the study, cephalexin was administered whenever a susceptible organism appeared in the urine. There was no effect upon the incidence of new bacteriuria, number of bacterial strains per urine specimen, or most importantly, incidence of febrile episodes [29]. The only change was a marked increase in antibiotic-resistant organisms. These investigations suggest that asymptomatic bacteriuria need not be treated as long as the catheter, short-term or long-term, remains in place. There are exceptions. One is if such a therapy is part of a plan to control a cluster of infections by a particular organism in a medical unit. Another is for patients who may be at high risk of serious complications (e.g. granulocytopenic patients, solid organ transplant patients, and pregnant women). A third exception includes patients undergoing urologic surgery. The final possible group is of patients undergoing other types of surgery, particularly those in whom prostheses may be left in place. Some patients undergoing long-term catheterization have recurrent obstructions of the catheter, which are mostly associated with infections by P. mirabilis and subsequent encrustation with struvite and apatite crystals. Unfortunately, daily catheter irrigation with normal saline appears to be ineffective in reducing obstructions [30]. Interestingly, methenamine preparations may reduce the incidence of obstruction, possibly because of biochemical alteration of salt solubility [31]. 4. Treatment of complications For the patient who develops fever and/or signs of bacteremia, the clinician should rule out sources outside the urinary tract, catheter obstruction, and, especially among men, periurethral infection. Urine and blood cultures should be performed. Many clinicians would empirically treat such patients with parenteral antibiotics to treat possible bacteremia from a bacteriuric species. Because of the likelihood of bacteria sequestered in a biofilm on the catheter surface, a reasonable decision may be to replace or remove the catheter during therapy of symptomatic catheter-associated bacteriuria, a move apparently supported by recent data [32]. For patients with increasing renal dysfunction or recalcitrant or recurring bacteremia or fever, a search for urinary stones may be helpful. Candiduria may develop in catheterized patients and its incidence is directly related to the duration of catheterization and hospitalization and to antibiotic use. Catheter-associated candiduria is generally asymptomatic and, because its natural history is not well-understood, its management is unclear. Removal of the catheter results in the disappearance of candiduria in up to 40% of patients; simply changing the catheter results in 20% clearance of candiduria. For asymptomatic patients whose candiduria persists or who must remain catheterized, appropriate management is a problem. A randomized trial of using fluconazole versus irrigation of the bladder with amphotericin B revealed similar eradication rates [33]. A group of investigators of candidal diseases reached consensus that, if possible, catheters should be removed from the urinary tracts of patients with candiduria and such patients should be treated before undergoing a genitourinary tract operative procedure. Furthermore, if non-krusei candidal cystitis were to be treated, oral fluconazole should be the choice [34]. Complications of

5 J.W. Warren / International Journal of Antimicrobial Agents 17 (2001) candiduria can develop and include fever, renal and perirenal abscesses, fungus balls, and in patients with genitourinary abnormalities, disseminated candidiasis. In these situations, systemic therapy with amphotericin B or fluconazole and appropriate surgical procedures are indicated. References [1] Daifuku R, Stamm W. Association of rectal and urethral colonization with urinary tract infection in patients with indwelling catheters. J Am Med Assoc 1984;252: [2] Stark RP, Maki DG. Bacteriuria in the catheterized patient. What quantitative level of bacteriuria is relevant? N Engl J Med 1984;311: [3] Platt R, Polk BF, Murdock B, et al. Risk factors for nosocomial urinary tract infection. Am J Epidemiol 1986;124: [4] Warren JW, Platt R, Thomas RJ, et al. Antibiotic irrigation and catheter-associated urinary-tract infections. N Engl J Med 1978;299:570. [5] Hartstein AI, Garber SB, Ward TT, et al. Nosocomial urinary tract infection: a prospective evaluation of 108 catheterized patients. Infect Control 1981;2: [6] Bryan C, Reynolds K. Hospital-acquired bacteremic urinary tract infection: epidemiology and outcome. J Urol 1984;132: [7] Platt R, Polk BF, Murdock B, et al. Mortality associated with nosocomial urinary tract infection. N Engl J Med 1982;307:637. [8] Stamm WE. Catheter-associated urinary tract infections: epidemiology, pathogenesis, and prevention. Am J Med 1991;91(Suppl 3B):65S 71. [9] Warren JW, Steinberg L, Hebel JR, et al. The prevalence of urethral catheterization in Maryland nursing homes: estimates for the United States. Arch Intern Med 1989;149: [10] Warren JW, Tenney JH, Hoopes JM, et al. A prospective microbiologic study of bacteriuria in patients with chronic indwelling urethral catheters. J Infect Dis 1982;146: [11] Warren JW, Damron D, Tenney JH, et al. Fever, bacteremia, and death as complications of bacteriuria in women with longterm urethral catheters. 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Clean intermittent catheterization: safe, cost-effective bladder management for male residents of VA nursing homes. J Am Geriatr Soc 1995;43: [25] Andersen JT, Heisterberg L, Hebjorn S, et al. Suprapubic versus transurethral bladder drainage after coloposuspension/vaginal repair. Acta Obstet Gynecol Scand 1985;64: [26] Johnson JR, Roberts PL, Olsen RJ, et al. Prevention of catheterassociated urinary tract infection with a silver oxide-coated urinary catheter: clinical and microbiologic correlates. J Infect Dis 1990;162: [27] Riley D, Classen D, Stevens L, et al. A large randomized clinical trial of a silver-impregnated urinary catheter: lack of efficacy and staphylococcal superinfection. Am J Med 1995;98: [28] Garibaldi RA, Mooney BR, Epstein BJ, et al. An evaluation of daily bacteriologic monitoring to identify preventable episodes of catheter-associated urinary tract infection. Infect Control 1982;3: [29] Warren JW, Anthony WC, Hoopes JM, et al. Cephalexin for susceptible bacteriuria in afebrile, long-term catheterized patients. J Am Med Assoc 1982;248: [30] Hoopes J, Muncie H, Warren J, et al. Once-daily irrigation of long-term urethral catheters with normal saline. Lack of benefit. Arch Intern Med 1989;149: [31] Norberg A, Norberg B, Parkhede U, et al. Randomized doubleblind study of prophylactic methenamine hippurate treatment of patients with indwelling catheters. Eur J Clin Pharmacol 1980;18: [32] Raz R, Schiller D, Nicolle LE. Replacement of catheter improves the outcome of patients with permanent urinary catheter and symptomatic bacteriuria. 1998; Abstracts of the 38 th Annual ICAAC p. 532 [33] Jacobs L, Skidmore E, Freeman K, et al. Oral fluconazole compared with bladder irrigation with amphotericin B for treatment of fungal urinary tract infections in elderly patients. CID 1996;22:30 5. [34] Edwards JE, Jr, Bodey GP, Bowden RA, et al. 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