US Pharm. 2010;35(8):HS-6-HS-10.
Urinary tract infections (UTIs) are the most common nosocomially acquired infection in the United States in both the hospital and the long-term care setting.1-3 In most hospitals, catheter-associated (CA) bacteriuria accounts for approximately 40% of all nosocomially acquired infections annually.1-4 Although multiple risk factors exist, 80% of nosocomial infections are CA.5 This is not implausible considering that 20% to 25% of patients admitted to an acute-care hospital receive catheterization at some point during their stay.1,2,6 UTIs also account for 15% of nosocomial bacteremia.7 These infections have been estimated to cost from $600 to more than $2,800 per event, and most are largely avoidable with preventive practices.6,8 In 2008, the Centers for Medicare and Medicaid Services initiated the practice of denying compensation for such events.9 This action has likely contributed to the recent updating of existing guidelines to focus on the prevention, diagnosis, and management of CA-UTIs.9,10 This article will review key guideline initiatives.
Identification of Infection
Distinguishing between a bacterial presence (or colonization) and a symptomatic infectious process is the basis for treatment decisions. The 2009 Infectious Diseases Society of America (IDSA) guidelines define CA-UTI as “the presence of symptoms or signs compatible with UTI with no other identified source of infection along with ≥103 colony-forming units (cfu)/mL of ≥1 bacterial species” from a catheterized or previously catheterized (≤48 hours) urine sample.4 The CDC's definition of CA-UTI is comparable, but it requires a positive urinalysis if the culture is between 103 cfu/mL and 105 cfu/mL.11
Common symptoms associated with CA-UTIs may include fever, flank pain, costovertebral tenderness, hematuria (nonmenstrual), and new-onset delirium. There also may be increased frequency or tenderness upon urination after the catheter is removed.4,12 In patients with spinal cord injuries, the signs and symptoms of CA-UTI may include discomfort or pain over the kidney or bladder or during urination; new-onset incontinence; fever; increased spasticity or hyperreflexia; malaise; lethargy; or a sense of unease, according to the National Institute on Disability and Rehabilitation Research Consensus Statement.13
The IDSA has classified the absence of symptoms in the presence of bacteria (≥105 cfu/mL of ≥1 bacterial species in the catheterized patient) as asymptomatic CA bacteriuria (CA-ASB).4 In most CA-ASB studies, treatment resulted in only a temporary sterilization of the urine, not eradication of the bacteria. Moreover, once the catheter was removed, 33% to 50% of patients with bacteriuria cleared on their own.14 Thus, treatment of CA-ASB increases the risk of development of drug resistance or adverse events associated with an unnecessary therapeutic agent.14 Therefore, urine samples from asymptomatic catheterized patients should not be screened for infection. Exceptions include pregnant women; patients undergoing urologic surgery, with or without a prosthesis; attempts to control an extremely resistant nosocomial bacterial strain within a patient care unit; and immunosuppressed patients in whom infection could be related to a serious complication, such as bacteremia.4,14
Risk Factors for CA-UTI
The risk of introducing bacteria into the urine after a single catheterization is 1% to 5%.13 Some CA-UTIs are similar to uncomplicated UTIs in that the bacteria are associated with the individual's own intestinal or skin flora.4,13 These organisms are introduced into the urinary tract with catheter insertion. Thus, catheterization should be limited.4,13,15
Since the incidence of bacteriuria associated with indwelling catheterization is between 3% and 8% per day, it is essential to limit the duration of catheterization.4 Once catheter placement has occurred, contamination from external sources offers another possible mechanism for infection. External contamination can occur when health care providers use improper techniques to empty the catheter bag. Improper emptying can result in the backup of urine into the tubing.4,15 Also, the external environment can cross-contaminate the catheter. Contamination may occur in the bag, as well as in the exterior or interior of the tubing. Contamination of the exterior of the tubing is more common.4
Furthermore, some bacterial pathogens can produce a biofilm, which is an adherent layer of accumulated microorganisms and their extracellular products.4,13,15 The biofilm protects the organism against both host defenses and antibiotic therapy. Migration to the bladder can occur within 1 to 3 days.4 Biofilms also contribute to an increased risk of antimicrobial resistance, as the microorganisms are able to share genetic material at a faster rate.4 Additionally, some bacterial biofilms have the ability to alter the urine pH, facilitating the development of catheter encrustations. These encrustations obstruct urine flow and increase the risk of CA-UTI.
The duration of catheterization is also a risk factor. Nearly all patients who are catheterized for more than 30 days (long-term catheterization) will experience bacteriuria.4 These severely ill patients also are at risk for upper-UT inflammation, which increases the risk of bacteremia. Long-term catheterization infections are often polymicrobial, which requires a broader treatment spectrum.4,16 Additionally, not only does catheterization increase the risk of bacteremia, it also increases the risk of other complications, like deep venous thrombosis, as a result of limited mobility. These complications result in extended stays and increased costs.17
General CA-UTI risk factors include nonuse of systemic antibiotics; female sex (likely anatomical); catheter insertion outside the operating room, or deviation from the optimal sterile environment; absence of a catheter chamber clip; rapidly fatal underlying illness; older age; diabetes; and elevated serum creatinine at the time of diagnosis.4,15,16 These last several events are associated with breaches in or decreased response to the host's defense mechanisms, which also increases the risk of infection. Even after the catheter is removed, the patient remains at risk for bacteriuria for at least 24 hours.18
Prevention
Although 25% to 75% of CA-UTIs are believed to be preventable, a study conducted in 2005 determined that 56% of the 600 U.S. hospitals surveyed had no monitoring system in place to identify the number of catheters placed and that 74% did not identify the duration of use.9,19 Utilization of prevention initiatives is the key component for reducing costs and risks associated with these infections.
Since the primary prevention method is to limit catheter use, the development of an indication checklist and educational sessions on catheter use for health care providers are key initiatives.4,13,15,19 When catheterization is necessary, the use of an intermittent or suprapubic catheter (after a surgical procedure) should be considered as an alternative to a short-term (<30 days' duration) or long-term catheter.4 Condom catheters in males are common in Veterans Administration hospitals. These catheters, along with portable bladder scanners, have been shown to help reduce infection rates.19 Unfortunately, condom catheters cannot be used on men with small penises, those with ulcerated or irritated skin, or those with obstructed urine flow. Although the use of antimicrobial-impregnated catheters has not been shown to reduce the risk of CA-UTIs, nitrofurazone and silver alloy-coated catheters may reduce or delay the risk of bacteriuria. More studies are currently needed to determine the place of antimicrobial-coated catheters in the treatment and prevention of CA-UTIs.4,12,20
Should an indwelling catheter be deemed necessary, aseptic techniques and sterile equipment should be utilized for both insertion and maintenance of the closed catheter system.4 Initial cleaning of the meatal area prior to insertion can reduce bacterial transfer; however, whether daily cleansing after insertion offers reduced infection rates remains controversial.14 After insertion, the use of universal precautions--such as gloves and gowns--is recommended when urine is emptied.4,15 The second key initiative is to limit the duration of use.4,15 Interventions that have been shown to be effective include a nurse-led multidisciplinary catheter-rounds team, automatic stop orders, and reminders in the hospital computer system.4,14
To reduce the risk of contamination and backflow, all catheter systems should have a closed drainage system and drain below the level of the patient's bladder.4 Additionally, prophylactic antibiotics should not be added to urine collection bags, as no benefit has been established.4
Treatment
Urine Culture Techniques: The presence of pyuria or odorous or cloudy urine should not be associated with CA-UTI in asymptomatic patients, yet their absence decreases the likelihood of infection.4 Ideally, when a urine culture from a patient with a short-term indwelling catheter is warranted, the urine sample should be obtained directly through the catheter port or by using a sterile needle to puncture the catheter tubing.4 In patients with long-term indwelling catheters, the catheter ideally should be changed prior to the collection of the laboratory sample. This has been shown to reduce the incidence of sample contamination by catheter biofilm. If this is not possible, the catheter should be changed early in the treatment course.12,21
Antimicrobial Therapy: Routine use of prophylactic antimicrobials at the time of catheter removal or replacement has not been shown to be beneficial. One prospective, randomized trial involving more than 500 patients examined the use of three doses of trimethoprim/sulfamethoxazole versus no treatment and found a significant decrease in rates of both CA-UTI and bacteriuria with treatment; more studies are needed, however. Women with CA-ASB after 48 hours of a short-term catheter removal may be considered candidates for prophylactic treatment with trimethoprim/sulfamethoxazole.
Antimicrobial agent selections for a CA-UTI depend on the Gram stain and culture results. Routinely, 60% to 80% of CA-UTIs have gram-negative origins, including Escherichia coli, Klebsiella, Pseudomonas, Proteus, and Enterobacter species. The other 20% to 40% are gram-positive, with Enterococcus and Staphylococcus species being the most common.22 Empiric treatment should consider factors that increase the risk of drug resistance, including the duration of hospital stay, prior antimicrobial agents, residence at a long-term care facility, and local resistance patterns.4,23
Urinary fluoroquinolones such as ciprofloxacin and levofloxacin may be considered in patients with mild-to-moderate infections who do not have alterations in mental status and are considered hemodynamically stable.16,23 Moxifloxacin is not recommended, as it does not achieve effective concentrations in the urine. Broad-spectrum cephalosporins such as ceftriaxone or cefepime may be used.16,23 In patients with urosepsis or those who are hemodynamically unstable (hypothermia, tachycardia >90/min, tachypnea >20/min or Pco2 <33 mm Hg, leukocytosis [>12 x 109 L] or leukopenia [<4 x 109 L]), a broader-spectrum drug like piperacillin-tazobactam or a carbapenem may be necessary. These agents also may be prescribed for Enterococcus species that are susceptible to ampicillin (TABLE 1).
In cases of CA-ASB with Candida, catheter removal should be a sufficient treatment. If symptomatic candiduria is identified, blood cultures should be drawn to assess for systemic infection. Rather than ascending from the kidneys, Candida often descends from a systemic blood infection. Systemic treatment with oral fluconazole 200 mg/day for 2 weeks is recommended for cystitis. For pyelonephritis, oral fluconazole 200 mg/day to 400 mg/day for 2 weeks may be administered for susceptible strains. Alternatives for resistant strains of Candida include flucytosine 25 mg/kg four times daily or amphotericin B 0.3 mg/kg/day to 0.7 mg/kg/day systemically.23
Treatment of CA-UTIs may include the use of antibiotics for 3 days in women under 65 years of age whose catheter has been removed; otherwise, a period of 7 days may be prescribed when a quick response is identified. A study comparing levofloxacin 750 mg once daily for 5 days with ciprofloxacin 500 mg twice daily for 10 days found that these agents were equally effective. Thus, a duration of therapy of 5 days may be used with levofloxacin.24 If the patient's response to therapy is delayed, the duration may be extended to 10 to 14 days.4
Conclusion
Most CA-UTIs are costly and preventable. The development and implementation of protocols based on current guidelines not only will reduce inappropriate uses, but also may lessen antibiotic resistance. When catheterization is necessary, the duration of use should be limited. If infection occurs, empiric therapy should be based on the suspected pathogens and the hospital's antibiogram. Once cultures are available, antibiotic selections should be refined to narrow the antimicrobial spectrum. Treatment duration should be limited to 7 to 14 days, depending upon treatment response. Catheter removal is a key factor, as catheterization not only increases a patient's risk of nosocomial infection, but also heightens the risk of other complications, resulting in extended stays and increased costs.
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