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CATHETER-ASSOCIATED URINARY TRACT INFECTIONS
URINARY TRACT INFECTIONS
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CATHETER-ASSOCIATED URINARY TRACT INFECTIONS John W. Warren, MD
Each year millions of urethral catheters are put in place in acute care hospitals and nursing homes across the United States. Indications for urethral catheterization can be grouped into four categories: (1)surgery, (2) urine output measurement, (3) urine retention, and (4) urinary incontinence. With the exception of occasional trauma and urethritis, virtually all complications of urinary catheterization are results of consequent bacteriuria. Most catheter-associated urinary tract infections (UTIs) are endogenous, that is, from the patient's own colonic flora, and the catheter predisposes to UTI in several ways. The indwelling catheter offers conduits to bacterial entry along its external and internal surfaces. 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.z0Biofilm has been demonstrated on catheters,", 71 and organisms contained within the biofilm seem to be well protected from antibiotics and the flow of urine.sz Uroepithelial cells of catheterized patients may transiently allow greater numbers of bacteria to adhere to their surfaces, a phenomenon that may precede the onset of bacteriuria.13 As a foreign body, the catheter may blunt adequate antibacterial polymorphonuclear leukocyte function.'zoFinally, catheter drainage is often imperfect, and volumes of urine may remain in the bladder. SHORT-TERM CATHETERIZATION Epidemiology
Between 15% to 25% of patients in general hospitals may have a catheter inserted sometime during their stay.2sThe duration of catheterization is the most
From the Department of Medicine, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, Maryland
INFECTIOUS DISEASE CLINICS OF NORTH AMERICA VOLUME 11 * NUMBER 3 * SEPTEMBER 1997
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important risk factor for the development of catheter-associated bacteriuria.21, 2y, 4y, 8s Fortunately, most catheters in hospitals are in place for only a short time; the mean and median durations in most reports are between 2 and 4 days.21,25, 2 v , 4 9 , 1 1 3 At 3% to 10% incidence per day, 10% to 30% of catheterized patients develop bacteriuria?I,25, 4y A multivariate by Platt et a1 revealed nine independent risk factors for catheter-associated bacteriuria: Duration of catheterization Absence of use of a urinemeter Microbial colonization of the drainage bag Diabetes mellitus Absence of antibiotic use Female patient Indications for other than surgery or output measurement Abnormal serum creatinine Errors in catheter care Although not assessed in the study above, periurethral colonization with potential uropathogens is also an important risk factor. Eighteen percent of patients with periurethral colonization with gram-negative rods or enterococci Indeed, developed bacteriuria compared to 5% of patients not so colonized.2c1 progressive uropathogen colonization of the urethra occurs in catheterized patients, particularly women.5o,94 The potential space between the external surface of the catheter and the urethral mucosa has become the most prominent entry point for bacteria, causing 70% to 80% of episodes of bacteriuria in women.12 Even after removal of a catheter, the patient may remain at risk for bacteriuria for at least 24 hours,', 29 possibly because of the increased urethral colonization associated with the indwelling catheter.
Bacteriuria
Most bacteria first identified in the catheterized urinary tract at low concentrations will reach a density of 100,000 cfu/mL or more over succeeding days.Io2 To establish a diagnosis, many investigators have required this concentration; others have selected lower densities. Most bacteriurias in short-term catheterizations are of single organisms, but as many as 15% may be polymi~robial.~~ Most catheter-associated bacteriurias have accompanying ~ y u r i a . ~ ~ Among short-term catheterized patients, E. coli is the most frequent bacteriuric species, although it comprises only about 25% of isolates. As with infections in other complicated urinary tracts, recognized E. coli virulence factors are not highly prevalent among the strains causing catheter-associated UTI.2,35 For instance, even from febrile catheter-associated UTIs, only 10% of the isolated E. coli strains carry P fimbriae, the adhesins commonly found in pyelonephritogenic strains in uncomplicated urinary tracts.35Other common organisms are enterococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter sp, Staphylococcus epidermidis, and Staphylococcus au~eus.",65,H5, Yeast may be isolatedzh,85, l L 3 particularly when antibiotics are in use and are increasing in incidence." A reminder should be noted here. Patients with urinary catheters in place often are ill with acute underlying diseases. These patients may be at risk for bloodstream infection from other sources, and the clinician should be on the
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lookout for organisms in the urine that represent hematogenous seeding of the kidney, not ascending infection associated with the catheter. Two organisms that commonly infect kidneys hematogenously are S. aureus and Cundidu sp3, m, 70; some investigators consider Salmonella and Pseudornonas spp to have similar properties!* Recognition of these hematogenous UTIs is crucial. Management of patients with these disseminated infections in many cases is different from those with catheter-associated infections. Complications
Most episodes of bacteriuria associated with short-term catheters are asymptomatic; however, fevers or other symptoms of UTI occur in up to 30% of patients.zz,25, zy Less than 5% of catheter-associated bacteriurias, however, will be 22, 23, 32,45 Nevertheless, because of the large number complicated by bacteremia.y,lh. of catheterized patients, nosocomial UTIs are the source of up to 15% of nosocomial bloodstream infection^.^, 45 Mortality attributed to bacteremia from nosocomial bacteriuria is less than 15% and most deaths are in patients with severe underlying diseases.' At autopsy, patients with catheter-associated bacteriuria may have acute pyelonephritis, urinary stones, or perinephric abscesses.', z3 Platt et a1 demonstrated a threefold increase in mortality associated with bacteriuria even after a multivariate analysis excluded 20 other prospectively monitored variablesH4 LONG-TERM CATHETERIZATION
Epidemiology
At any given time more than 100,000 patients in American nursing homes have urethral catheters in place,1y,114 and many will be catheterized for months and years. The incidence of bacteriuria seems to be of the same magnitude as that found in hospitals, that is, about 3% to 10% a day.Il5 Therefore, most patients will be bacteriuric by the end of 30 days' catheteri~ation:~,7h, 95 a convenient dividing line between short-term catheterization, usually in hospitals in which the thrust of medical care should be toward prevention of bacteriuria, and long-term catheterization, usually in nursing homes in which most catheterized patients most of the time are bacteriuric. Bacteriuria
The near universal prevalence of bacteriuria is caused by not only the high incidence of new bacteriuric episodes but also the ability of some bacterial strains to persist for weeks and months in the catheterized urinary tract."", These phenomena result in polymicrobial bacteriuria in up to 95% of urine specimens from long-term catheterized patients.'"" l l u , 'I5 Infecting organisms include common uropathogens such as E. coli, P. aeruginosa, and P. mirabilis and less familiar species such as Providenciu stuartii and Morganella rnorganii.19, 7h,97, l1O, 115 Although virtually always used for diagnosis, urine obtained through the catheter may not always reflect bladder urine. Bergquist found that one quarter of paired samples of catheter and bladder urine (obtained by suprapubic aspiration) demonstrated that catheter urine often had organisms not present in
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bladder urine.i This suggests that organisms colonizing the catheter, perhaps under a biofilm, may not in all cases colonize the bladder itself or that bacteriostatic or bactericidal features of the bladder or bladder urine may not function well in the catheter. Complications
Complications of long-term catheter-associated bacteriuria fall into two categories. The first includes symptomatic UTIs such as seen with short-term catheterization, that is, fever, acute pyelonephritis, bacteremia, and death. The second comprises problems more specific to long-term catheterization: catheter obstruction, urinary tract stones, local periurinary infections, chronic renal inflammation, renal failure and, over years, bladder cancer. Two-thirds of febrile episodes in aged long-term catheterized patients are caused by UTI."O However, the actual incidence is surprisingly low, about 1 Most such episodes last for febrile episode per 100 days of a day or less and resolve without antibiotic therapy or catheter change."" Acute pyelonephritis is undoubtedly the source of some of these febrile episodes. Moreover, autopsies have revealed acute pyelonephritis in more than one third of patients dying with long-term catheters in place."' UTIs are the most common source of bacteremias in nursing homesh7and the indwelling urethral catheter increases the risk for bacteremia by almost 60 times.H9Even "nonpathogens" such as P. stuartii or M. rnorganii may cause ba~teremia.6~. lo In long-term catheterized patients, catheter obstruction may be a 6x The material that obstructs urinary catheters is composed of bacteproblem.4R, ria, glycocalyx, Tamm-Horsfall protein, and precipitated 63, 71, 77 P. rnirabilis bacteriuria is associated with catheter obstru~tion,4~,probably because of this organism's potent urease,4I, which hydrolyzes urea to ammonia, increasing urine pH and causing crystallization of struvite and apatite in the catheter lumen. Electron microscopy has demonstrated these crystals within the bacterial biofilm.", 77 Although some catheter obstructions are associated with the onset of fever, most are not,11upossibly because of early detection and removal of the obstructed catheter. The urease of P. rnirabilis (and possibly other organisms) may also cause formation of "infection stones."60,Iu4 Bladder stones may crust around the catheter balloon and are relatively benign.z8Renal stones, however, may be more serious and are associated with chronic pyelonephritis.los, Chronic renal inflammation is common in long-term catheterized persons and is related directly to the duration of catheterization.ih,112 The more specific chronic pyelonephritis, that is, chronic renal inflammation with deformed calyces and overlying parenchymal scarring, is also related to duration of catheterization but is found in only a minority of chronically inflamed kidneys and is associated with hydronephrosis or, as noted, renal stones.Ios,'I2 Complications of long-term catheterization in men may include urethritis, urethral fistulae, epididymitis, scrota1 abscess, prostatitis, and prostatic abscess.'os For patients catheterized for years, bladder cancer may occur.42,5h PREVENTIVE TECHNIQUES Postponement of Bacteriuria
Only two catheter hygiene principles are universally recommended. One is to keep the closed catheter system closed. A plastic collection bag fused to the
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distal end of the collection tube means urine can always be contained within a lumen “closed” to the contaminated environment. Most catheter systems now have ports in the distal catheter for needle aspiration of urine. Urine specimens should be obtained by needle and syringe without opening the catheter-collection tube junction,14,21. 34. 83. 113. 119 The second principle is to remove the catheter as soon as possible. Two prospective studies, with criteria for continued catheterization developed a priori, demonstrated that a substantial proportion of days of catheterization are ~nnecessary.~~, 3y Increasing attention is being directed at removing catheters earlier.36,l I y If the catheter can be removed before bacteriuria develops, postponement of bacteriuria becomes prevention. Although many logical modifications have been applied to the urethral catheter and its care, none have uniformly and markedly improved on the ability of the closed catheter system to postpone bacteriuria. These unsuccessful ventures have included local antibacterial agents as bladder irrigation or as a component of the catheter itself. An example of the latter is the use of silvercoated catheters, intended to exploit the antibacterial effect of silver ions. Several randomized trials have been performed and have yielded conflicting results.40, 54, ss, 57, R7, q5 The largest studies did not show a lower incidence of bacteriuria associated with silver-coated 87 The use of systemic antibiotics, however, has been shown repeatedly to postpone bacteriuria in the catheterized patient. As a matter of fact, in the general hospital, about 80% of patients are administered systemic antibiotics sometime during their catheterization. For the most part, these antibiotics are administered because of prophylaxis for surgical operations or treatment of nonurinary infections, not as prophylaxis against catheter-associated UTI. These studies and the few randomized trials that have been performed indicate that systemic antibiotics are associated with a diminished incidence of bacteriuria. Those which followed patients long enough, however, revealed that antibiotics were effective for the first several days and then resistant organisms began to appear in the urine.”, 76 Consequently, most authorities feel that antibiotics to postpone bacteriuria are not indicated because of side effects, cost, and emergence of resistant bacteria in the patient and in the medical unit4h, loo, lox; however, there may be exceptions to this generalization. For instance, patients at high risk for the complications of catheter-associated bacteriuria, for example, renal transplant18and granulocytopenic patients, might benefit from antibiotic prophylaxis during short-term catheterization. Prevention of the Complications of Bacteriuria
If bacteriuria cannot be postponed indefinitely, might treatment of bacteriuria in the asymptomatic patient prevent complications such as fever, acute pyelonephritis, and bacteremia? The data that are available suggest that this approach is not particularly useful. Garibaldi et aP2 noted in hospitalized patients that symptomatic catheter-associated UTIs tended to occur on the first day when bacteriuria appeared. Therefore, in many patients, there is no asymptomatic bacteriuria to treat in order to prevent symptomatic UTI. Still, what about those catheter-associated bacteriurias that are asymptomatic? The data from Garibaldi et a1 suggest that, if one were to assume that antibiotics were 100% effective in preventing symptomatic UTIs, 250 urine cultures would be required to prevent one symptomatic UTI. In long-term catheterized patients, the practice of antibiotic therapy of asymptomatic bacteriuria has
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been tested in a prospective trial. There was no effect on the incidence of febrile episodes and, indeed, the only change was a marked increase in antibioticresistant organisms.'"'' These investigations suggest that, in general, asymptomatic bacteriuria need not be treated as long as the catheter, short-term or long-term, remains in place; however, several exceptions may pertain. One is for particular bacterial strains in a given institution that are causing a high incidence of bacteremia from catheter-associated bacteriuria; Serrntia mnrcescens has been such an organism.45,l U 1 A second is if such therapy is part of a plan to control a cluster of infections by a particular organism in a medical unit. A third is for those patients who may be at high risk for serious complications; these may include granulocytopenic patients, solid organ transplant patients, and pregnant women. A fourth includes patients who undergo urologic surgery (and perhaps other types of surgery, particularly those involving prostheses). These possibilities should be evaluated by controlled trials. Some patients with long-term catheters have recurrent obstructions of the catheter, which in many is associated with infections by Proteus mirnbilis and consequent encrustation with struvite and apatite crystals. The simple approach of daily catheter irrigation with normal saline seems to be ineffective in diminishing obstructions.31Interestingly, methenamine preparations may diminish the incidence of obstruction, possibly because of biochemical alteration of salt ~olubility.'~ The question exists whether catheter-associated bacteriuria should be treated after the removal of the catheter. The natural history is not all together clear, although it should be understood in the context of the host. For instance, of hospitalized women 65 years of age or less, 74% resolved their bacteriuria spontaneously within 14 days following catheter removal, compared with only 4% of older women.2i This study reported that the administration of antibiotics markedly improved the clearance rate among older women. However, the longterm effect of eradicating postcatheterization asymptomatic bacteriuria, for example, in terms of symptomatic UTI, is unclear. Long-term studies of the natural history and antibiotic therapy of post-catheterization bacteriuria would be welcomed.
Prevention of Urethral Catheterization
The above studies indicate that if a catheter remains in place, clinicians can only postpone bacteriuria but that once it occurs, clinicians seem unable to prevent its complications. Clearly the most effective means to prevent catheterassociated bacteriuria-and its complications-is to prevent catheterization itself. Several devices have been explored as options to the urethral catheter.
Condom Catheters For men with urinary incontinence, condom-type collectors that empty through a collection tube into a drainage bag have been widely used. Urine within these condom catheters may develop high concentrations of organisms, and the urethra and skin may be colonized with ur~pathogens.'~,~~', h4 To distinguish bladder bacteriuria from skin contamination, careful collection of urine in a new condom by well-trained individuals is necessary.iz,R1 Although no properly designed controlled trials have been performed, parallel studies in the same
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institution of condom catheters and urethral catheters suggest a substantially lower incidence of bacteriuria with condom catheter^.'^, Ro Intermittent Catheterization
Insertion and removal of a sterile or clean catheter several times a day provides periodic bladder emptying4,*,'16 and has become the standard of care for patients with spinal injuries. Nevertheless, because the incidence of bacteriuria is about 1% to 3% per catheterization, by 2 or 3 weeks most patients undergoing intermittent catheterization are bacteriuric. The 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 f~nction.~, Oral antibiotics and methenamine compounds and bladder instillations of povidone iodine and chlorhexidine preparations have been shown to postpone bacteriuria for short periods in intermittently catheterized patients.43,R2 Resistant organisms, however, appear (in some studies even in the placebo group, a finding attributed to nosocomial spread of resistant organisms from the antibiotic The effects of systemic or bladder antimicrobial agents on longterm consequences, antibiotic resistance, adverse reactions, and medical costs remain unclear. Suprapubic Catheterization
Because the anterior abdominal skin carries a lower density of bacteria than the periurethral area, suprapubic catheterization has been used in several types of surgery and seems to yield lower rates of bacteriuria.-?,'Ih For comfort and convenience, significantly more patients may prefer suprapubic over urethral catheter^.'^ Additional well-designed trials should identify different populations now using short-term and long-term urethral catheters that might benefit from suprapubic catheters. lntraurethral Catheters
Devices that are totally contained within the urethra have been introduced to relieve urinary retention because of benign prostatic hypertr~phy.~?, 74 Early reports have suggested low incidences of bacteriuria and symptomatic infection over weeks and months of use. Properly designed studies of these devices are awaited with interest. TREATMENT OF COMPLICATIONS Symptomatic Bacterial UTI
For the patient who develops fever or signs of bacteremia, sources outside the urinary tract should be sought and catheter obstruction and periurethral infection (including epididymitis and prostatitis) should be ruled out. After cultures of urine and blood, these patients should be treated with parenteral antibiotics, the selection based on urine Gram stain and knowledge of organisms in the medical unit. Seven to 10 days of therapy is usually sufficient and need not all be parenteral. The occasional patient with bladder symptoms, such as
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lower abdominal pain without fever or other evidence of systemic infection, may benefit from an oral antibiotic. Because of the likelihood of bacteria sequestered in a biofilm on the catheter surface, a reasonable decision might be to replace or remove the catheter during antibiotic therapy, although the few data available are not particularly supportive of this concept.s1
Candiduria
Candiduria may develop in catheterized patients, and its incidence is directly related to the duration of catheterization, hospitalization, and antibiotic use.zhThe incidence of catheter-associated candiduria seems to be increasing, particularly in recent years.6It is generally asymptomatic, but complications can include fungus balls in the bladder or renal pelvis, fever,',38,7"renal infection including renal and perirenal abscesses,106 and disseminated candidiasis. Management of asymptomatic catheter-associated candiduria is unclear. Removal of the catheter results in the disappearance of candiduria in about one third of patients. For asymptomatic patients whose candiduria persists or who must remain catheterized, several management techniques have been tried. Irrigation with amphotericin B at various concentrations has been used over the last several decades37,'I7 as have short courses of intravenous amphotericin B. Fluconazole has been a noteworthy addition to our armamentarium. A small prospective study comparing oral fluconazole with amphotericin B irrigation demonstrated that although equivalent proportions of patients were cleared of their candiduria, significantly more patients receiving amphotericin B irrigation died within 1 month than did those receiving oral fluconazole.3RThese investigators speculated that in some of their patients, the candiduria was evidence of preexisting candidemia. This interpretation underscores the fact that the indwelling catheter acts not only as a source for ascending candiduria, but also as a marker for the patient ill with acute and chronic diseases who is at risk for disseminated candidiasis from nonurinary sources. In the latter case, the observed candiduria may represent a hematogenously infected kidney, a possibility that should always be considered in the acutely ill, febrile patient.
Prevention of Patient-PatientTransmission
Once a catheter-associated UTI has developed, transmission among patients may lead to clusters of nosocomial infections. Fifteen percent or more of nosocomial bacteriurias may occur in such c1usters.lo,9" Furthermore, plasmids encoding antibiotic resistance can move between bacteria,". 92 and such plasmid transfer has been a phenomenon suspected to occur in urine of catheterized patients.9K DNA transmission has been demonstrated in urine at room temperature for 4 to 8 hours in vitro9'; these conditions are those in the collection bag of the patient with polymicrobial bacteriuria. To prevent or control nosocomial outbreaks, it is important to use gloves and wash hands between patientst5, and to segregate catheterized patients from each other.58To limit the number of patients at risk, urethral catheterization and its duration should be minimized, and excellent catheter hygiene maintaining the integrity of the closed catheter system should be practiced.
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SUMMARY
Millions of urethral catheters are used each year. This device subverts several host defenses to allow bacterial entry at the rate of 3% to 10% incidence per day, and its presence encourages the organism’s persistent residence in the urinary tract. Most catheter-associated bacteriurias are asymptomatic. The complications in short-term catheterized patients include fever, acute pyelonephritis, bacteremia, and death; patients with long-term catheters in place are at risk for these complications and catheter obstruction, urinary tract stones, local periurinary infections, chronic renal inflammation, chronic pyelonephritis, and, over years, bladder cancer. The closed catheter system has been a magnificant step forward in the prevention of catheter-associated bacteriuria. Indeed, only two catheter principles are universally recommended: keep the closed catheter system closed and remove the catheter as soon as possible. Most modifications of the closed catheter system have not improved markedly on its ability to postpone bacteriuria. On first inspection, systemic antibiotics seem to be an exception to this rule, but their use results in infection of the bladder with resistant organisms, including candida. This and the effect of side effects on the patient and emergence of resistant bacteria in the medical unit have led most authorities to conclude that antibiotics are not useful for prevention of bacteriuria, nor for treatment of bacteriuria in the asymptomatic catheterized patient. For symptomatic patients, usually with fever or signs of sepsis, treatment of bacteriuria with appropriate systemic antibiotics and removal or replacement of the urethral catheter are indicated. Gloves, hand washing, and segregation of catheterized patients can minimize nosocomial clusters. Because clinicians can only postpone bacteriuria, and once it occurs, clinicians seem unable to prevent its complications, methodologies other than urethral catheters should be used for urine drainage assistance whenever possible. These options include condom, intermittent, suprapubic, and intraurethral catheterization for appropriate patients. The few data available suggest that each one of these catheterization options yields a lower incidence of bacteriuria-and its consequent complications-than urethral catheterization. References 1. Ang BSP, Telenti A, King B, et al: Candidemia from a urinary tract source: Microbiological aspects and clinical significance. Clin Infect Dis 17662-666, 1987 2. Amundsen S, Wang C, Schwan W, et al: Role of Escherichia coli adhesins in urethral colonization of catheterized patients. J Urol 140:651-655, 1988 3. Arpi M, Renneberg J: The clinical significance of Staphylococcus auyeus bacteriuria. J Urol 697-700, 1984 4. Bakke A: Physical and psychological complications in patients treated with clean intermittent catheterization. Scand J Urol Nephrol 15O(Suppl):1-61, 1993 5. Bergquist D, Bronnestam R, Hedelin H, et al: The relevance of urinary sampling methods in patients with indwelling Foley catheters. Br J Urol 52:92-95, 1980 6. Bonsema D, Adams J, Pallares R, et al: Secular trends in rates and etiology of nosocomial urinary tract infections at a university hospital. J Urol 150:414416, 1993 7. Britt MR, Garibaldi RA, Miller WA, et al: Antimicrobial prophylaxis for catheterassociated bacteriuria. Antimicrob Agents Chemother 11:240, 1977 8. Brun-Buisson C, Philippon A, Ansquer M, et al: Transferable enzymatic resistance to third-generation cephalosporins during nosocomial outbreak of multiresistant Klebsiella pneumoniae. Lancet ii:302-306, 1987
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9. Bryan C, Reynolds K: Hospital-acquired bacteremic urinary tract infection: Epidemiology and outcome. J Urol 132494-498, 1984 10. Bukhari S, Sanderson P, Richardson D, et al: Endemic cross-infection in an acute medical ward. J Hosp Infect 24261-271, 1993 11. Cox AJ, Hukins DWL, Sutton TM: Infection of catheterised patients: Bacterial colonisation of encrusted Foley catheters shown by scanning electron microscopy. Urol Res 17:349-352, 1989 12. Daifuku R, Stamm W: Association of rectal and urethral colonization with urinary tract infection in patients with indwelling catheters. JAMA 252:2028-2030, 1984 13. Daifuku R, Stamm W: Bacterial adherence to bladder uroepithelial cells in catheterassociated urinary tract infection. N Engl J Med 3141208-1213, 1986 14. DeGroot-Kosolcharoen J, Guse R, Jones JM: Evaluation of a urinary catheter with a preconnected closed drainage bag. Infect Control Hosp Epidemiol9:72-76, 1988 15. Ehrenkranz NJ, Alfonso BC: Failure of bland soap handwash to prevent hand transfer of patient bacteria to urethral catheters. Infect Control Hosp Epidemiol 12654-662, 1991 16. Emori T, Banejee S, Culver D, et al: Nosocomial infections in elderly patients in the United States, 19861990. Am J bled 91:289>293S, 1991 17. Fierer J, Ekstrom M: An outbreak of Providencia stuartii urinary tract infections: Patients with condom catheters are a reservoir of the bacteria. JAMA 245:1553-1555, 1981 18. Fox BC, Sollinger HW, Belzer FO, et a1 A prospective, randomized, double-blind study of trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation: Clinical efficacy, absorption of trimethoprim-sulfamethoxazole,effects on the microflora, and the cost-benefit of prophylaxis. Am J Med 89:255-274, 1990 19. Garibaldi RA, Brodine S, Matsumiya S: Infections among patients in nursing homes. Policies, prevalence and problems. N Engl J Med 305:731-735, 1981 20. Garibaldi RA, Burke JP, Britt MR, et al: Meatal colonization and catheter-associated bacteriuria. N Engl J Med 303:316-318, 1980 21. Garibaldi RA, Burke JP, Dickman ML, et a1 Factors predisposing to bacteriuria during indwelling urethral catheterization. N Engl J Med 291:215, 1974 22. Garibaldi RA, Mooney BR, Epstein BJ, et a1 An evaluation of daily bacteriologic monitoring to identify preventable episodes of catheter-associated urinary tract infection. Infect Control 3:466-470, 1982 23. Gordon D, Bune A, Grime B, et a1 Diagnostic criteria and natural history of catheterassociated urinary tract infections after prostatectomy. Lancet 1:1269-1271, 1983 24. Gribble M, Puterman M Prophylaxis of urinary tract infection in persons with recent spinal cord injury: A prospective, randomized, double-blind, placebo-controlled study of trimethoprim-sulfamethoxazole. Am J Med 95:141-152, 1993 25. Haley RW, Hooton TM, Culver DH, et al: Nosocomial infections in U.S. hospitals, 1975-1976: Estimated frequency by selected characteristics of patients. Am J Med 70947-959, 1981 26. Hamory BH, Wenzel RP: Hospital-associated candiduria: Predisposing factors and review of the literature. J Urol 120:444448, 1978 27. Harding GKM, Nicolle LE, Ronald AR, et a1 How long should catheter-acquired urinary tract infection in women be treated? A randomized controlled study. Ann Intern Med 114:713-719, 1991 28. Hardy AG: Complications of the indwelling urethral catheter. Paraplegia 6:5, 1968 29. Hartstein AI, Garber SB, Ward TT, et al: Nosocomial urinary tract infection: A prospective evaluation of 108 catheterized patients. Infect Control 2:380-386, 1981 30. Hirsh DD, Fainstein V, Musher DM: Do condom catheter collecting systems cause urinary tract infection? JAMA 242:340-341, 1979 31. 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 149:441443, 1989 32. Horan T, Culver D, Gaynes R, et al: Nosocomial infections in surgical patients in the United States, January 1986 to June 1992. Infect Control Hosp Epidemiol 1473-80, 1994
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33. Horgan AF, Prasad 8, Waldron DJ, et al: Acute urinary retention: Comparison of suprapubic and urethral catheterisation. Br J Urol 70149-151, 1992 34. Huth TS, Burke JP, Larsen RA, et al: Clinical trial of junction seals for the prevention of urinary catheter-associated bacteriuria. Arch Intern Med 152307-812, 1992 35. Ikaheimo R, Siitonen A, Karkkainen U, et a1 Virulence characteristics of Escherichin coli in nosocomial urinary tract infection. Clin Infect Dis 16:785-791, 1993 36. Irani J, Fauchery A, Dore B, et a1 Systematic removal of catheter 48 hours following transurethral resection and 24 hours following transurethral incision of prostate: A prospective randomized analysis of 213 patients. J Urol 153:1537-1539, 1995 37. Jacobs L, Skidmore E, Cardoso L, et al: Bladder irrigation with amphotericin B for treatment of fungal urinary tract infections. Clin Infect Dis 18:313-318, 1994 38. 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. Clin Infect Dis 2230-35, 1996 39. Jain P, Parada JP, David A, et al: Overuse of the indwelling urinary tract catheter in hospitalized medical patients. Arch Intern Med 155:1425-1429, 1995 40. Johnson JR, Roberts PL, Olsen RJ, et aI: Prevention of catheter-associated urinary tract infection with a silver oxide-coated urinary catheter: Clinical and microbiologic correlates. J Infect Dis 1621145-1150, 1990 41. Jones B, Mobley H: Genetic and biochemical diversity of ureases of Pvoteus, Providencin and Movgunella species isolated from urinary tract infection. Infect Immun 55:21982203, 1987 42. Kaufman JM, Fam B, Jacobs S, et al: Bladder cancer and squamous metaplasia in spinal cord injury patients. J Urol 118967-971, 1977 43. Kevorkian CG, Merritt JL, Ilstrup DM: Methenamine mandelate with acidification: An effective urinary antiseptic in patients with neurogenic bladder. Mayo Clin Proc 59523-529, 1984 44. King RB, Carlson CE, Mervine J, et al: Clean and sterile intermittent catheterization methods in hospitalized patients with spinal cord injury. Arch Phys Med Rehabil 73~798-802, 1992 45. Krieger JN, Kaiser DL, Wenzel RP: Urinary tract etiology of bloodstream infections in hospitalized patients. J Infect Dis 148:57-62, 1983 46. Kunin CM: Detection, prevention and management of urinary tract infections, ed 4. Philadelphia, Lea & Febiger, 1987, pp 245-297 47. Kunin CM: Blockage of urinary catheters: Role of microorganisms and constituents of the urine on formation of encrustations. J Clin Epidemiol42:835-842, 1989 48. Kunin CM, Chin QF, Chambers S: Formation of encrustations on indwelling urinary catheters in the elderly: A comparison of different types of catheter materials in "blockers" and "nonbiockers." J Urol 1385399-902, 1987 49. Kunin CM, McCormack RC: Prevention of catheter-induced urinary-tract infections by sterile closed drainage. N Engl J Med 274:1155, 1966 50. Kunin CM, Steele C: Culture of the surface of urinary catheters to sample urethral flora and study the effect of antimicrobial therapy. J Clin Microbiol 21:902-908, 1985 51. Kumazawa J, Matsumoto T The dipstick test in the diagnosis of UTI and the effect of pretreatment catheter exchange in catheter-associated UTI. Infection 20:S157S159, 1992 52. Ladd TI, Schmiel D, Nickel JC, et al: The use of a radiorespirometric assay for testing the antibiotic sensitivity of catheter-associated bacteria. J Urol 138:1451-1456, 1987 53. Lee B, Crossley K, Gerding D: The association between Staphylococcus auveus bacteremia and bacteriuria. Am J Med 65:303-306, 1978 54. Liedberg H, Lundeberg T: Silver alloy coated catheters reduce catheter-associated bacteriuria. Br J Urol 65:379-381, 1990 55. Liedberg H, Lundeberg T, Ekman P: Refinements in the coating of urethral catheters reduces the incidence of catheter-associated bacteriuria. Eur Urol 17:236-240, 1990 56. Locke JR, Hill DE, Walzer Y: Incidence of squamous cell carcinoma in patients with long-term catheter drainage. J Urol 1331034-1035, 1985 57. Lundeberg T: Prevention of catheter-associated urinary-tract infections by use of silver-impregnated catheters. Lancet 21031, 1986
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58. Maki D, Hennekens C, Bennet J: Prevention of catheter-associated urinary tract infection. JAMA 221:1270-1271, 1972 59. Maki DG, Hennekens CG, Phillips CW, et al: Nosocomial urinary tract infection with Serratia viarcescens: An epidemiologic study. J Infect Dis 128:579-587, 1973 60. McLean R, Nickel JC, Noakes VC, et al: An in vitro ultrastructural study of infectious kidney stone genesis. Infect Immun 49:805-811, 1985 61. Mobley HLT, Hausinger RP: Microbial ureases: Significance, regulation, and molecular characterization. Microb Rev 53:85-108, 1989 62. Mobley HLT, Jones B, Jerse AE: Cloning of urease gene sequences from Provideticia stnartii. Infect Immun 54:161-169, 1986 63. Mobley HLT, Warren JW: Urease-positive bacteriuria and obstruction of long-term urinary catheters. J Clin Microbiol 25:2216-2217, 1987 64. Montgomerie JZ, Morrow JW: Pseudomonas colonization in patients with spinal cord injury. Am J Epidemiol 108:328-336, 1978 65. Morrison AJ, Wenzel RP: Nosocomial urinary tract infections due to enterococcus. Arch Intern Med 146:1549-1551, 1986 66. Mountokalakis T, Skounakis M, Tselentis J: Short-term versus prolonged systemic antibiotic prophylaxis in patients treated with indwelling catheters. J Urol 134:506508, 1985 67. Muder R, Brennen C, Wagener M, et al: Bacteremia in a long-term care facility: A five year prospective study of 163 consecutive episodes. Clin Infect Dis 14:647-654, 1992 68. Muncie HL Jr, Warren JW: Reasons for replacement of long-term urethral catheters: Implications for randomized trials. J Urol 143507-509, 1990 69. Musher D, Thorsteinsson S, Airola V 11: Quantitative Urinalysis: Diagnosing urinary tract infection in men. JAMA 2362069-2072, 1976 70. Nassoura 2, Ivtury R, Simon R, et al: Candiduria as an early marker of disseminated infection in critically ill surgical patients: The role of fluconazole therapy. J Trauma 35:290-295, 1993 71. Nickel JC, Gristina P, Costerton JW: Electron microscopic study of an infected Foley catheter. Can J Surg 28:50-52, 1985 72. Nicolle LE, Harding GKM, Kennedy J, et al: Urine specimen collection with external devices for diagnosis of bacteriuria in elderly incontinent men. J Clin ?Aicrobiol 26:1115-1119, 1988 73. Nielsen KK, Klarskov P, Nordling J, et al: The intraprostatic spiral: New treatment for urinary retention. Br J Urol 65:500-503, 1990 74. Nissenkorn I, Richter S, Slutzker D A simple, self-retaining intraurethral catheter for treatment of prostatic obstruction. Eur Urol 18:286-289, 1990 75. Norberg A, Norberg B, Parkhede U, et al: Randomized double-blind study of prophylactic methenamine hippurate treatment of patients with indwelling catheters. Eur J Clin Pharmacol 18:497-500, 1980 76. Nyren P, Runeberg L, Kostiala AI, et al: Prophylactic methenamine hippurate or nitrofurantoin in patients with an indwelling urinary catheter. Ann Clin Res 13:1621, 1981 77. Ohkawa M, Sugata T, Sawaki M, et al: Bacterial and crystal adherence to the surfaces of indwelling urethral catheters. J Urol 143:717-721, 1990 78. O’Kelly TJ, Mathew A, Ross S, et al: Optimum method for urinary drainage in major abdominal surgery: A prospective randomized trial of suprapubic versus urethral catheterization. Br J Surg 821367-1368, 1995 79. Ouslander JG, Greengold B, Chen S: Complications of chronic indwelling urinary catheters among male nursing home patients: A prospective study. J Urol 138:11911195, 1987 80. Ouslander J, Greengold B, Chen S: External catheter use and urinary tract infections among incontinent male nursing home patients. J Am Geriatr Soc 35:1063-1070, 1987 81. Ouslander JG, Greengold BA, Silverblatt FJ, et al: An accurate method to obtain urine for culture in men with external catheters. Arch Intern Med 147286-288, 1987 82. Pearman JW, Bailey M, Riley LP: Bladder instillations of trisdine compared with catheter introducer for reduction of bacteriuria during intermittent catheterisation of patients with acute spinal cord trauma. Br J Urol67483-490, 1991
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83. Platt R, Murdock B, Polk BF, et al: Reduction of mortality associated with nosocomial urinary tract infection. Lancet 1:1893-1897, 1983 84. Platt R, Polk BF, Murdock B, et al: Mortality associated with nosocomial urinary tract infection. N Engl J Med 307637, 1982 85. Platt R, Polk BF, Murdock B, et al: Risk factors for nosocomial urinary tract infection. Am J Epidemiol 124:977-985, 1986 86. Rahav G, Pinco E, Silbaq F, et al: Molecular epidemiology of catheter-associated bacteriuria in nursing home patients. J Clin Microbiol 32:1031-1034, 1994 87. Riley D, Classen D, Stevens L, et al: A large randomized clinical trial of a silverimpregnated urinary catheter: Lack of efficacy and staphylococcal superinfection. Am J Med 98:349-356, 1995 88. Rubin R, Tolkoff-Rubin N, Cotran R Urinary tract infection, pyelonephritis, and reflux nephropathy. In Brenner, Rector (eds): The Kidney 11, ed 3. Philadelphia, WB Saunders 24:1085, 1986 89. Rudman D, Hontanosas A, Cohen 2, et al: Clinical correlates of bacteremia in a Veterans Administration extended care facility. J Am Geriatr Soc 36:726-732, 1988 90. Schaberg DR, Haley RW, Highsmith AK, et al: Nosocomial bacteriuria: A prospective study of case clustering and antimicrobial resistance. Ann Intern Med 93420424,1980 91. Schaberg DR, Highsmith AK, Wachsmith IK: Resistance plasmid transfer by Sevvntin marcescens in urine. Antimicrob Agents Chemother 11:449450, 1977 92. Schaberg DR, Rubens CE, Alford RH, et al: Evolution of antimicrobial resistance and nosocomial infection: Lessons from the Vanderbilt experience. Am J Med 70:445448, 1981 93. Schaberg DR, Zervos MI: Nosocomial urinary tract infection: Comprehensive Therapy 12:8-11,-1986 94. Schaeffer AT. Chmiel 1: Urethral meatal colonization in the Dathoeenesis of catheterassociated bacteriuria: J Urol 130:1096-1099, 1983 95. Schaeffer AJ, Story KO, Johnson SM. Effect of silver oxide/trichloroisocyanuric acid antimicrobial urinary drainage system on catheter-associated bacteriuria. J Urol 139~69-73,1988 96. Schiotz HA, Malme PA, Tanbo TG: Urinary tract infections and asymptomatic bacteriuria after vaginal plastic surgery: A comparison of suprapubic and transurethral catheters. Acta Obstet Gynecol Scand 68:453455, 1989 97. Senay H, Goetz MB: Epidemiology of bacteremic urinary tract infections in chronically hospitalized elderly men. J Urol 145:1201-1204, 1991 98. Shlaes DM, Lehman M-H, Currie-McCumber CA, et al: Prevalence of colonization with antibiotic resistant gram-negative bacilli in a nursing home care unit: The importance of cross-colonization as documented by plasmid analysis. Infect Control 7538-545, 1986 99. Siegman-Igra Y, Kulka T, Schwartz D, et al: Polymicrobial and monomicrobial bacteraemic urinary tract infection. J Hosp Infect 28:49-56, 1994 100. Slade N, Gillespie W A The Urinary Tract and the Catheter: Infection and Other Problems. New York, John Wiley & Sons, 1985 101. Stamm WE, Martin SM, Bennett JV: Epidemiology of nosocomial infections due to gram-negative bacilli: Aspects relevant to development and use of vaccines. J Infect Dis 136(suppl):151-160, 1977 102. Stark RP, Maki DG: Bacteriuria in the catheterized patient: What quantitative level of bacteriuria is relevant? N Engl J Med 311:560-564, 1984 103. Steward DK, Wood GL, Cohen RL, et al: Failure of the urinalysis and quantitative urine culture in diagnosing symptomatic urinary tract infections in patients with long-term urinary catheters. Am J Infect Control 13:154-160, 1985 104. Takeuchi H, Takayama H, Konishi T, et a1 Scanning electron microscopy detects bacteria within infection stones. J Urol 132:67-69, 1984 105. Tribe CR, Silver J R Renal failure in paraplegia. London, Pitman Medical Publishing Co, 1969 106. Wainstein M, Graham R, Resnick M: Predisposing factors of systemic fungal infections of the genitourinary tract. J Urol 154:160-163, 1995
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107. Warren JW: Providencia stuartii: A common cause of antibiotic-resistant bacteriuria in patients with long-term indwelling catheters. Rev Infect Dis 8:6147, 1986 108. Warren JW: The catheter and urinary tract infection. Med Clin North Am 75:481493, 1991 109. Warren JW, Anthony WC, Hoopes JM, et al: Cephalexin for susceptible bacteriuria in afebrile, long-term catheterized patients. JAMA 248:454-458, 1982 110. Warren JW, Damron D, Tenney JH, et al: Fever, bacteremia, and death as complications of bacteriuria in women with long-term urethral catheters. J Infect Dis 155:11511158, 1987 111. Warren JW, Muncie HL Jr, Hall-Craggs M: Acute pyelonephritis associated with the bacteriuria of long-term catheterization: A prospective clinico-pathological study. J Infect Dis 158:1341-1346, 1988 112. Warren JW, Muncie HL Jr, Hebel JR, et al: Long-term urethral catheterization increases risk of chronic pyelonephritis and renal inflammation. J Am Geriatr SOC 42:1286-1290, 1994 113. Warren JW, Platt R, Thomas RJ, et al: Antibiotic irrigation and catheter-associated urinary tract infections. N Engl J Med 299570, 1978 114. 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 149:15351537, 1989 115. Warren JW, Tenney JH, Hoopes JM, et al: A prospective microbiologic study of bacteriuria in patients with chronic indwelling urethral catheters. J Infect Dis 146:719723, 1982 116. Webb RJ, Lawson AL, Neal DE: Clean intermittent self-catheterisation in 172 adults. Br J Urol 6520-23, 1990 117. Wong-Beringer A, Jacobs R, Guglielmo J: Treatment of funguria. JAMA 26727802785, 1992 118. Wyndaele J-1, Maes D Clean intermittent self-catheterization: A 12-year followup. J Urol 143:906-908, 1990 119. Zimakoff JDA, Pontoppidan 8, Larsen SO, et al: The management of urinary catheters: Compliance of practice in Danish hospitals, nursing homes and home care to national guidelines. Scand J Urol Nephrol 29:299-309, 1995 120. Zimmerli W, Lew PD, Waldvogel FA: Pathogenesis of foreign body infection. Evidence for a local granulocyte defect. J Clin Invest 73:1191-1200, 1984
Address reprint requests to John W. Warren, MD Division of Infectious Diseases University of Maryland School of Medicine 10 South Pine Street, Rm 9-00 Baltimore, MD 21201
0891-5520/97 $0.00
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CATHETER-ASSOCIATED URINARY TRACT INFECTIONS John W. Warren, MD
Each year millions of urethral catheters are put in place in acute care hospitals and nursing homes across the United States. Indications for urethral catheterization can be grouped into four categories: (1)surgery, (2) urine output measurement, (3) urine retention, and (4) urinary incontinence. With the exception of occasional trauma and urethritis, virtually all complications of urinary catheterization are results of consequent bacteriuria. Most catheter-associated urinary tract infections (UTIs) are endogenous, that is, from the patient's own colonic flora, and the catheter predisposes to UTI in several ways. The indwelling catheter offers conduits to bacterial entry along its external and internal surfaces. 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.z0Biofilm has been demonstrated on catheters,", 71 and organisms contained within the biofilm seem to be well protected from antibiotics and the flow of urine.sz Uroepithelial cells of catheterized patients may transiently allow greater numbers of bacteria to adhere to their surfaces, a phenomenon that may precede the onset of bacteriuria.13 As a foreign body, the catheter may blunt adequate antibacterial polymorphonuclear leukocyte function.'zoFinally, catheter drainage is often imperfect, and volumes of urine may remain in the bladder. SHORT-TERM CATHETERIZATION Epidemiology
Between 15% to 25% of patients in general hospitals may have a catheter inserted sometime during their stay.2sThe duration of catheterization is the most
From the Department of Medicine, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, Maryland
INFECTIOUS DISEASE CLINICS OF NORTH AMERICA VOLUME 11 * NUMBER 3 * SEPTEMBER 1997
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important risk factor for the development of catheter-associated bacteriuria.21, 2y, 4y, 8s Fortunately, most catheters in hospitals are in place for only a short time; the mean and median durations in most reports are between 2 and 4 days.21,25, 2 v , 4 9 , 1 1 3 At 3% to 10% incidence per day, 10% to 30% of catheterized patients develop bacteriuria?I,25, 4y A multivariate by Platt et a1 revealed nine independent risk factors for catheter-associated bacteriuria: Duration of catheterization Absence of use of a urinemeter Microbial colonization of the drainage bag Diabetes mellitus Absence of antibiotic use Female patient Indications for other than surgery or output measurement Abnormal serum creatinine Errors in catheter care Although not assessed in the study above, periurethral colonization with potential uropathogens is also an important risk factor. Eighteen percent of patients with periurethral colonization with gram-negative rods or enterococci Indeed, developed bacteriuria compared to 5% of patients not so colonized.2c1 progressive uropathogen colonization of the urethra occurs in catheterized patients, particularly women.5o,94 The potential space between the external surface of the catheter and the urethral mucosa has become the most prominent entry point for bacteria, causing 70% to 80% of episodes of bacteriuria in women.12 Even after removal of a catheter, the patient may remain at risk for bacteriuria for at least 24 hours,', 29 possibly because of the increased urethral colonization associated with the indwelling catheter.
Bacteriuria
Most bacteria first identified in the catheterized urinary tract at low concentrations will reach a density of 100,000 cfu/mL or more over succeeding days.Io2 To establish a diagnosis, many investigators have required this concentration; others have selected lower densities. Most bacteriurias in short-term catheterizations are of single organisms, but as many as 15% may be polymi~robial.~~ Most catheter-associated bacteriurias have accompanying ~ y u r i a . ~ ~ Among short-term catheterized patients, E. coli is the most frequent bacteriuric species, although it comprises only about 25% of isolates. As with infections in other complicated urinary tracts, recognized E. coli virulence factors are not highly prevalent among the strains causing catheter-associated UTI.2,35 For instance, even from febrile catheter-associated UTIs, only 10% of the isolated E. coli strains carry P fimbriae, the adhesins commonly found in pyelonephritogenic strains in uncomplicated urinary tracts.35Other common organisms are enterococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter sp, Staphylococcus epidermidis, and Staphylococcus au~eus.",65,H5, Yeast may be isolatedzh,85, l L 3 particularly when antibiotics are in use and are increasing in incidence." A reminder should be noted here. Patients with urinary catheters in place often are ill with acute underlying diseases. These patients may be at risk for bloodstream infection from other sources, and the clinician should be on the
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lookout for organisms in the urine that represent hematogenous seeding of the kidney, not ascending infection associated with the catheter. Two organisms that commonly infect kidneys hematogenously are S. aureus and Cundidu sp3, m, 70; some investigators consider Salmonella and Pseudornonas spp to have similar properties!* Recognition of these hematogenous UTIs is crucial. Management of patients with these disseminated infections in many cases is different from those with catheter-associated infections. Complications
Most episodes of bacteriuria associated with short-term catheters are asymptomatic; however, fevers or other symptoms of UTI occur in up to 30% of patients.zz,25, zy Less than 5% of catheter-associated bacteriurias, however, will be 22, 23, 32,45 Nevertheless, because of the large number complicated by bacteremia.y,lh. of catheterized patients, nosocomial UTIs are the source of up to 15% of nosocomial bloodstream infection^.^, 45 Mortality attributed to bacteremia from nosocomial bacteriuria is less than 15% and most deaths are in patients with severe underlying diseases.' At autopsy, patients with catheter-associated bacteriuria may have acute pyelonephritis, urinary stones, or perinephric abscesses.', z3 Platt et a1 demonstrated a threefold increase in mortality associated with bacteriuria even after a multivariate analysis excluded 20 other prospectively monitored variablesH4 LONG-TERM CATHETERIZATION
Epidemiology
At any given time more than 100,000 patients in American nursing homes have urethral catheters in place,1y,114 and many will be catheterized for months and years. The incidence of bacteriuria seems to be of the same magnitude as that found in hospitals, that is, about 3% to 10% a day.Il5 Therefore, most patients will be bacteriuric by the end of 30 days' catheteri~ation:~,7h, 95 a convenient dividing line between short-term catheterization, usually in hospitals in which the thrust of medical care should be toward prevention of bacteriuria, and long-term catheterization, usually in nursing homes in which most catheterized patients most of the time are bacteriuric. Bacteriuria
The near universal prevalence of bacteriuria is caused by not only the high incidence of new bacteriuric episodes but also the ability of some bacterial strains to persist for weeks and months in the catheterized urinary tract."", These phenomena result in polymicrobial bacteriuria in up to 95% of urine specimens from long-term catheterized patients.'"" l l u , 'I5 Infecting organisms include common uropathogens such as E. coli, P. aeruginosa, and P. mirabilis and less familiar species such as Providenciu stuartii and Morganella rnorganii.19, 7h,97, l1O, 115 Although virtually always used for diagnosis, urine obtained through the catheter may not always reflect bladder urine. Bergquist found that one quarter of paired samples of catheter and bladder urine (obtained by suprapubic aspiration) demonstrated that catheter urine often had organisms not present in
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bladder urine.i This suggests that organisms colonizing the catheter, perhaps under a biofilm, may not in all cases colonize the bladder itself or that bacteriostatic or bactericidal features of the bladder or bladder urine may not function well in the catheter. Complications
Complications of long-term catheter-associated bacteriuria fall into two categories. The first includes symptomatic UTIs such as seen with short-term catheterization, that is, fever, acute pyelonephritis, bacteremia, and death. The second comprises problems more specific to long-term catheterization: catheter obstruction, urinary tract stones, local periurinary infections, chronic renal inflammation, renal failure and, over years, bladder cancer. Two-thirds of febrile episodes in aged long-term catheterized patients are caused by UTI."O However, the actual incidence is surprisingly low, about 1 Most such episodes last for febrile episode per 100 days of a day or less and resolve without antibiotic therapy or catheter change."" Acute pyelonephritis is undoubtedly the source of some of these febrile episodes. Moreover, autopsies have revealed acute pyelonephritis in more than one third of patients dying with long-term catheters in place."' UTIs are the most common source of bacteremias in nursing homesh7and the indwelling urethral catheter increases the risk for bacteremia by almost 60 times.H9Even "nonpathogens" such as P. stuartii or M. rnorganii may cause ba~teremia.6~. lo In long-term catheterized patients, catheter obstruction may be a 6x The material that obstructs urinary catheters is composed of bacteproblem.4R, ria, glycocalyx, Tamm-Horsfall protein, and precipitated 63, 71, 77 P. rnirabilis bacteriuria is associated with catheter obstru~tion,4~,probably because of this organism's potent urease,4I, which hydrolyzes urea to ammonia, increasing urine pH and causing crystallization of struvite and apatite in the catheter lumen. Electron microscopy has demonstrated these crystals within the bacterial biofilm.", 77 Although some catheter obstructions are associated with the onset of fever, most are not,11upossibly because of early detection and removal of the obstructed catheter. The urease of P. rnirabilis (and possibly other organisms) may also cause formation of "infection stones."60,Iu4 Bladder stones may crust around the catheter balloon and are relatively benign.z8Renal stones, however, may be more serious and are associated with chronic pyelonephritis.los, Chronic renal inflammation is common in long-term catheterized persons and is related directly to the duration of catheterization.ih,112 The more specific chronic pyelonephritis, that is, chronic renal inflammation with deformed calyces and overlying parenchymal scarring, is also related to duration of catheterization but is found in only a minority of chronically inflamed kidneys and is associated with hydronephrosis or, as noted, renal stones.Ios,'I2 Complications of long-term catheterization in men may include urethritis, urethral fistulae, epididymitis, scrota1 abscess, prostatitis, and prostatic abscess.'os For patients catheterized for years, bladder cancer may occur.42,5h PREVENTIVE TECHNIQUES Postponement of Bacteriuria
Only two catheter hygiene principles are universally recommended. One is to keep the closed catheter system closed. A plastic collection bag fused to the
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distal end of the collection tube means urine can always be contained within a lumen “closed” to the contaminated environment. Most catheter systems now have ports in the distal catheter for needle aspiration of urine. Urine specimens should be obtained by needle and syringe without opening the catheter-collection tube junction,14,21. 34. 83. 113. 119 The second principle is to remove the catheter as soon as possible. Two prospective studies, with criteria for continued catheterization developed a priori, demonstrated that a substantial proportion of days of catheterization are ~nnecessary.~~, 3y Increasing attention is being directed at removing catheters earlier.36,l I y If the catheter can be removed before bacteriuria develops, postponement of bacteriuria becomes prevention. Although many logical modifications have been applied to the urethral catheter and its care, none have uniformly and markedly improved on the ability of the closed catheter system to postpone bacteriuria. These unsuccessful ventures have included local antibacterial agents as bladder irrigation or as a component of the catheter itself. An example of the latter is the use of silvercoated catheters, intended to exploit the antibacterial effect of silver ions. Several randomized trials have been performed and have yielded conflicting results.40, 54, ss, 57, R7, q5 The largest studies did not show a lower incidence of bacteriuria associated with silver-coated 87 The use of systemic antibiotics, however, has been shown repeatedly to postpone bacteriuria in the catheterized patient. As a matter of fact, in the general hospital, about 80% of patients are administered systemic antibiotics sometime during their catheterization. For the most part, these antibiotics are administered because of prophylaxis for surgical operations or treatment of nonurinary infections, not as prophylaxis against catheter-associated UTI. These studies and the few randomized trials that have been performed indicate that systemic antibiotics are associated with a diminished incidence of bacteriuria. Those which followed patients long enough, however, revealed that antibiotics were effective for the first several days and then resistant organisms began to appear in the urine.”, 76 Consequently, most authorities feel that antibiotics to postpone bacteriuria are not indicated because of side effects, cost, and emergence of resistant bacteria in the patient and in the medical unit4h, loo, lox; however, there may be exceptions to this generalization. For instance, patients at high risk for the complications of catheter-associated bacteriuria, for example, renal transplant18and granulocytopenic patients, might benefit from antibiotic prophylaxis during short-term catheterization. Prevention of the Complications of Bacteriuria
If bacteriuria cannot be postponed indefinitely, might treatment of bacteriuria in the asymptomatic patient prevent complications such as fever, acute pyelonephritis, and bacteremia? The data that are available suggest that this approach is not particularly useful. Garibaldi et aP2 noted in hospitalized patients that symptomatic catheter-associated UTIs tended to occur on the first day when bacteriuria appeared. Therefore, in many patients, there is no asymptomatic bacteriuria to treat in order to prevent symptomatic UTI. Still, what about those catheter-associated bacteriurias that are asymptomatic? The data from Garibaldi et a1 suggest that, if one were to assume that antibiotics were 100% effective in preventing symptomatic UTIs, 250 urine cultures would be required to prevent one symptomatic UTI. In long-term catheterized patients, the practice of antibiotic therapy of asymptomatic bacteriuria has
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been tested in a prospective trial. There was no effect on the incidence of febrile episodes and, indeed, the only change was a marked increase in antibioticresistant organisms.'"'' These investigations suggest that, in general, asymptomatic bacteriuria need not be treated as long as the catheter, short-term or long-term, remains in place; however, several exceptions may pertain. One is for particular bacterial strains in a given institution that are causing a high incidence of bacteremia from catheter-associated bacteriuria; Serrntia mnrcescens has been such an organism.45,l U 1 A second is if such therapy is part of a plan to control a cluster of infections by a particular organism in a medical unit. A third is for those patients who may be at high risk for serious complications; these may include granulocytopenic patients, solid organ transplant patients, and pregnant women. A fourth includes patients who undergo urologic surgery (and perhaps other types of surgery, particularly those involving prostheses). These possibilities should be evaluated by controlled trials. Some patients with long-term catheters have recurrent obstructions of the catheter, which in many is associated with infections by Proteus mirnbilis and consequent encrustation with struvite and apatite crystals. The simple approach of daily catheter irrigation with normal saline seems to be ineffective in diminishing obstructions.31Interestingly, methenamine preparations may diminish the incidence of obstruction, possibly because of biochemical alteration of salt ~olubility.'~ The question exists whether catheter-associated bacteriuria should be treated after the removal of the catheter. The natural history is not all together clear, although it should be understood in the context of the host. For instance, of hospitalized women 65 years of age or less, 74% resolved their bacteriuria spontaneously within 14 days following catheter removal, compared with only 4% of older women.2i This study reported that the administration of antibiotics markedly improved the clearance rate among older women. However, the longterm effect of eradicating postcatheterization asymptomatic bacteriuria, for example, in terms of symptomatic UTI, is unclear. Long-term studies of the natural history and antibiotic therapy of post-catheterization bacteriuria would be welcomed.
Prevention of Urethral Catheterization
The above studies indicate that if a catheter remains in place, clinicians can only postpone bacteriuria but that once it occurs, clinicians seem unable to prevent its complications. Clearly the most effective means to prevent catheterassociated bacteriuria-and its complications-is to prevent catheterization itself. Several devices have been explored as options to the urethral catheter.
Condom Catheters For men with urinary incontinence, condom-type collectors that empty through a collection tube into a drainage bag have been widely used. Urine within these condom catheters may develop high concentrations of organisms, and the urethra and skin may be colonized with ur~pathogens.'~,~~', h4 To distinguish bladder bacteriuria from skin contamination, careful collection of urine in a new condom by well-trained individuals is necessary.iz,R1 Although no properly designed controlled trials have been performed, parallel studies in the same
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institution of condom catheters and urethral catheters suggest a substantially lower incidence of bacteriuria with condom catheter^.'^, Ro Intermittent Catheterization
Insertion and removal of a sterile or clean catheter several times a day provides periodic bladder emptying4,*,'16 and has become the standard of care for patients with spinal injuries. Nevertheless, because the incidence of bacteriuria is about 1% to 3% per catheterization, by 2 or 3 weeks most patients undergoing intermittent catheterization are bacteriuric. The 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 f~nction.~, Oral antibiotics and methenamine compounds and bladder instillations of povidone iodine and chlorhexidine preparations have been shown to postpone bacteriuria for short periods in intermittently catheterized patients.43,R2 Resistant organisms, however, appear (in some studies even in the placebo group, a finding attributed to nosocomial spread of resistant organisms from the antibiotic The effects of systemic or bladder antimicrobial agents on longterm consequences, antibiotic resistance, adverse reactions, and medical costs remain unclear. Suprapubic Catheterization
Because the anterior abdominal skin carries a lower density of bacteria than the periurethral area, suprapubic catheterization has been used in several types of surgery and seems to yield lower rates of bacteriuria.-?,'Ih For comfort and convenience, significantly more patients may prefer suprapubic over urethral catheter^.'^ Additional well-designed trials should identify different populations now using short-term and long-term urethral catheters that might benefit from suprapubic catheters. lntraurethral Catheters
Devices that are totally contained within the urethra have been introduced to relieve urinary retention because of benign prostatic hypertr~phy.~?, 74 Early reports have suggested low incidences of bacteriuria and symptomatic infection over weeks and months of use. Properly designed studies of these devices are awaited with interest. TREATMENT OF COMPLICATIONS Symptomatic Bacterial UTI
For the patient who develops fever or signs of bacteremia, sources outside the urinary tract should be sought and catheter obstruction and periurethral infection (including epididymitis and prostatitis) should be ruled out. After cultures of urine and blood, these patients should be treated with parenteral antibiotics, the selection based on urine Gram stain and knowledge of organisms in the medical unit. Seven to 10 days of therapy is usually sufficient and need not all be parenteral. The occasional patient with bladder symptoms, such as
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lower abdominal pain without fever or other evidence of systemic infection, may benefit from an oral antibiotic. Because of the likelihood of bacteria sequestered in a biofilm on the catheter surface, a reasonable decision might be to replace or remove the catheter during antibiotic therapy, although the few data available are not particularly supportive of this concept.s1
Candiduria
Candiduria may develop in catheterized patients, and its incidence is directly related to the duration of catheterization, hospitalization, and antibiotic use.zhThe incidence of catheter-associated candiduria seems to be increasing, particularly in recent years.6It is generally asymptomatic, but complications can include fungus balls in the bladder or renal pelvis, fever,',38,7"renal infection including renal and perirenal abscesses,106 and disseminated candidiasis. Management of asymptomatic catheter-associated candiduria is unclear. Removal of the catheter results in the disappearance of candiduria in about one third of patients. For asymptomatic patients whose candiduria persists or who must remain catheterized, several management techniques have been tried. Irrigation with amphotericin B at various concentrations has been used over the last several decades37,'I7 as have short courses of intravenous amphotericin B. Fluconazole has been a noteworthy addition to our armamentarium. A small prospective study comparing oral fluconazole with amphotericin B irrigation demonstrated that although equivalent proportions of patients were cleared of their candiduria, significantly more patients receiving amphotericin B irrigation died within 1 month than did those receiving oral fluconazole.3RThese investigators speculated that in some of their patients, the candiduria was evidence of preexisting candidemia. This interpretation underscores the fact that the indwelling catheter acts not only as a source for ascending candiduria, but also as a marker for the patient ill with acute and chronic diseases who is at risk for disseminated candidiasis from nonurinary sources. In the latter case, the observed candiduria may represent a hematogenously infected kidney, a possibility that should always be considered in the acutely ill, febrile patient.
Prevention of Patient-PatientTransmission
Once a catheter-associated UTI has developed, transmission among patients may lead to clusters of nosocomial infections. Fifteen percent or more of nosocomial bacteriurias may occur in such c1usters.lo,9" Furthermore, plasmids encoding antibiotic resistance can move between bacteria,". 92 and such plasmid transfer has been a phenomenon suspected to occur in urine of catheterized patients.9K DNA transmission has been demonstrated in urine at room temperature for 4 to 8 hours in vitro9'; these conditions are those in the collection bag of the patient with polymicrobial bacteriuria. To prevent or control nosocomial outbreaks, it is important to use gloves and wash hands between patientst5, and to segregate catheterized patients from each other.58To limit the number of patients at risk, urethral catheterization and its duration should be minimized, and excellent catheter hygiene maintaining the integrity of the closed catheter system should be practiced.
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SUMMARY
Millions of urethral catheters are used each year. This device subverts several host defenses to allow bacterial entry at the rate of 3% to 10% incidence per day, and its presence encourages the organism’s persistent residence in the urinary tract. Most catheter-associated bacteriurias are asymptomatic. The complications in short-term catheterized patients include fever, acute pyelonephritis, bacteremia, and death; patients with long-term catheters in place are at risk for these complications and catheter obstruction, urinary tract stones, local periurinary infections, chronic renal inflammation, chronic pyelonephritis, and, over years, bladder cancer. The closed catheter system has been a magnificant step forward in the prevention of catheter-associated bacteriuria. Indeed, only two catheter principles are universally recommended: keep the closed catheter system closed and remove the catheter as soon as possible. Most modifications of the closed catheter system have not improved markedly on its ability to postpone bacteriuria. On first inspection, systemic antibiotics seem to be an exception to this rule, but their use results in infection of the bladder with resistant organisms, including candida. This and the effect of side effects on the patient and emergence of resistant bacteria in the medical unit have led most authorities to conclude that antibiotics are not useful for prevention of bacteriuria, nor for treatment of bacteriuria in the asymptomatic catheterized patient. For symptomatic patients, usually with fever or signs of sepsis, treatment of bacteriuria with appropriate systemic antibiotics and removal or replacement of the urethral catheter are indicated. Gloves, hand washing, and segregation of catheterized patients can minimize nosocomial clusters. Because clinicians can only postpone bacteriuria, and once it occurs, clinicians seem unable to prevent its complications, methodologies other than urethral catheters should be used for urine drainage assistance whenever possible. These options include condom, intermittent, suprapubic, and intraurethral catheterization for appropriate patients. The few data available suggest that each one of these catheterization options yields a lower incidence of bacteriuria-and its consequent complications-than urethral catheterization. References 1. Ang BSP, Telenti A, King B, et al: Candidemia from a urinary tract source: Microbiological aspects and clinical significance. Clin Infect Dis 17662-666, 1987 2. Amundsen S, Wang C, Schwan W, et al: Role of Escherichia coli adhesins in urethral colonization of catheterized patients. J Urol 140:651-655, 1988 3. Arpi M, Renneberg J: The clinical significance of Staphylococcus auyeus bacteriuria. J Urol 697-700, 1984 4. Bakke A: Physical and psychological complications in patients treated with clean intermittent catheterization. Scand J Urol Nephrol 15O(Suppl):1-61, 1993 5. Bergquist D, Bronnestam R, Hedelin H, et al: The relevance of urinary sampling methods in patients with indwelling Foley catheters. Br J Urol 52:92-95, 1980 6. Bonsema D, Adams J, Pallares R, et al: Secular trends in rates and etiology of nosocomial urinary tract infections at a university hospital. J Urol 150:414416, 1993 7. Britt MR, Garibaldi RA, Miller WA, et al: Antimicrobial prophylaxis for catheterassociated bacteriuria. Antimicrob Agents Chemother 11:240, 1977 8. Brun-Buisson C, Philippon A, Ansquer M, et al: Transferable enzymatic resistance to third-generation cephalosporins during nosocomial outbreak of multiresistant Klebsiella pneumoniae. Lancet ii:302-306, 1987
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9. Bryan C, Reynolds K: Hospital-acquired bacteremic urinary tract infection: Epidemiology and outcome. J Urol 132494-498, 1984 10. Bukhari S, Sanderson P, Richardson D, et al: Endemic cross-infection in an acute medical ward. J Hosp Infect 24261-271, 1993 11. Cox AJ, Hukins DWL, Sutton TM: Infection of catheterised patients: Bacterial colonisation of encrusted Foley catheters shown by scanning electron microscopy. Urol Res 17:349-352, 1989 12. Daifuku R, Stamm W: Association of rectal and urethral colonization with urinary tract infection in patients with indwelling catheters. JAMA 252:2028-2030, 1984 13. Daifuku R, Stamm W: Bacterial adherence to bladder uroepithelial cells in catheterassociated urinary tract infection. N Engl J Med 3141208-1213, 1986 14. DeGroot-Kosolcharoen J, Guse R, Jones JM: Evaluation of a urinary catheter with a preconnected closed drainage bag. Infect Control Hosp Epidemiol9:72-76, 1988 15. Ehrenkranz NJ, Alfonso BC: Failure of bland soap handwash to prevent hand transfer of patient bacteria to urethral catheters. Infect Control Hosp Epidemiol 12654-662, 1991 16. Emori T, Banejee S, Culver D, et al: Nosocomial infections in elderly patients in the United States, 19861990. Am J bled 91:289>293S, 1991 17. Fierer J, Ekstrom M: An outbreak of Providencia stuartii urinary tract infections: Patients with condom catheters are a reservoir of the bacteria. JAMA 245:1553-1555, 1981 18. Fox BC, Sollinger HW, Belzer FO, et a1 A prospective, randomized, double-blind study of trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation: Clinical efficacy, absorption of trimethoprim-sulfamethoxazole,effects on the microflora, and the cost-benefit of prophylaxis. Am J Med 89:255-274, 1990 19. Garibaldi RA, Brodine S, Matsumiya S: Infections among patients in nursing homes. Policies, prevalence and problems. N Engl J Med 305:731-735, 1981 20. Garibaldi RA, Burke JP, Britt MR, et al: Meatal colonization and catheter-associated bacteriuria. N Engl J Med 303:316-318, 1980 21. Garibaldi RA, Burke JP, Dickman ML, et a1 Factors predisposing to bacteriuria during indwelling urethral catheterization. N Engl J Med 291:215, 1974 22. Garibaldi RA, Mooney BR, Epstein BJ, et a1 An evaluation of daily bacteriologic monitoring to identify preventable episodes of catheter-associated urinary tract infection. Infect Control 3:466-470, 1982 23. Gordon D, Bune A, Grime B, et a1 Diagnostic criteria and natural history of catheterassociated urinary tract infections after prostatectomy. Lancet 1:1269-1271, 1983 24. Gribble M, Puterman M Prophylaxis of urinary tract infection in persons with recent spinal cord injury: A prospective, randomized, double-blind, placebo-controlled study of trimethoprim-sulfamethoxazole. Am J Med 95:141-152, 1993 25. Haley RW, Hooton TM, Culver DH, et al: Nosocomial infections in U.S. hospitals, 1975-1976: Estimated frequency by selected characteristics of patients. Am J Med 70947-959, 1981 26. Hamory BH, Wenzel RP: Hospital-associated candiduria: Predisposing factors and review of the literature. J Urol 120:444448, 1978 27. Harding GKM, Nicolle LE, Ronald AR, et a1 How long should catheter-acquired urinary tract infection in women be treated? A randomized controlled study. Ann Intern Med 114:713-719, 1991 28. Hardy AG: Complications of the indwelling urethral catheter. Paraplegia 6:5, 1968 29. Hartstein AI, Garber SB, Ward TT, et al: Nosocomial urinary tract infection: A prospective evaluation of 108 catheterized patients. Infect Control 2:380-386, 1981 30. Hirsh DD, Fainstein V, Musher DM: Do condom catheter collecting systems cause urinary tract infection? JAMA 242:340-341, 1979 31. 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 149:441443, 1989 32. Horan T, Culver D, Gaynes R, et al: Nosocomial infections in surgical patients in the United States, January 1986 to June 1992. Infect Control Hosp Epidemiol 1473-80, 1994
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107. Warren JW: Providencia stuartii: A common cause of antibiotic-resistant bacteriuria in patients with long-term indwelling catheters. Rev Infect Dis 8:6147, 1986 108. Warren JW: The catheter and urinary tract infection. Med Clin North Am 75:481493, 1991 109. Warren JW, Anthony WC, Hoopes JM, et al: Cephalexin for susceptible bacteriuria in afebrile, long-term catheterized patients. JAMA 248:454-458, 1982 110. Warren JW, Damron D, Tenney JH, et al: Fever, bacteremia, and death as complications of bacteriuria in women with long-term urethral catheters. J Infect Dis 155:11511158, 1987 111. Warren JW, Muncie HL Jr, Hall-Craggs M: Acute pyelonephritis associated with the bacteriuria of long-term catheterization: A prospective clinico-pathological study. J Infect Dis 158:1341-1346, 1988 112. Warren JW, Muncie HL Jr, Hebel JR, et al: Long-term urethral catheterization increases risk of chronic pyelonephritis and renal inflammation. J Am Geriatr SOC 42:1286-1290, 1994 113. Warren JW, Platt R, Thomas RJ, et al: Antibiotic irrigation and catheter-associated urinary tract infections. N Engl J Med 299570, 1978 114. 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 149:15351537, 1989 115. Warren JW, Tenney JH, Hoopes JM, et al: A prospective microbiologic study of bacteriuria in patients with chronic indwelling urethral catheters. J Infect Dis 146:719723, 1982 116. Webb RJ, Lawson AL, Neal DE: Clean intermittent self-catheterisation in 172 adults. Br J Urol 6520-23, 1990 117. Wong-Beringer A, Jacobs R, Guglielmo J: Treatment of funguria. JAMA 26727802785, 1992 118. Wyndaele J-1, Maes D Clean intermittent self-catheterization: A 12-year followup. J Urol 143:906-908, 1990 119. Zimakoff JDA, Pontoppidan 8, Larsen SO, et al: The management of urinary catheters: Compliance of practice in Danish hospitals, nursing homes and home care to national guidelines. Scand J Urol Nephrol 29:299-309, 1995 120. Zimmerli W, Lew PD, Waldvogel FA: Pathogenesis of foreign body infection. Evidence for a local granulocyte defect. J Clin Invest 73:1191-1200, 1984
Address reprint requests to John W. Warren, MD Division of Infectious Diseases University of Maryland School of Medicine 10 South Pine Street, Rm 9-00 Baltimore, MD 21201