Diagnosis and Management of Urinary Tract Infections in Older Women

Authors: 

Preeti N. Malani, MD

Citation: 

Pages 47 - 53

Educational Objectives
1. To identify risk factors associated with the development of UTI in older women
2. To understand the management of asymptomatic bacteriuria
3. To be able to recommend antimicrobial treatment for UTI in older women
4. To understand the major side effects and drug interactions associated with antimicrobials used to treat UTI

ACCREDITATION
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 1.0 category 1 credit toward the AMA Physician’s Recognition Award. Each physician should claim only those hours of credit that he/she actually spent in the educational activity. Valid May 1 - July 31, 2005. Estimated time: 1 hour

FULL DISCLOSURE POLICY AFFECTING CME ACTIVITIES
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or provider has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The presenting faculty reported the following: Dr. Malani has indicated that she has not received financial support for consultation, research or evaluation or has a financial interest relevant to this article. No faculty member has indicated that their presentation will include information on off-label products.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review of educational format design and approach. Please review the complete prescribing information of specific drugs or combination of drugs, including indications, contraindications, warnings and adverse effects before administering pharmacologic therapy to patients.

Urinary tract infections (UTIs) are among the most common infectious diseases in older women. Urinary tract infections in community-dwelling older women differ in terms of causative agents, risk factors, and treatment from those noted in women living in long-term care facilities. Escherichia coli remains the most common pathogen; however, gram-negative bacilli are prominent in residents of long-term care facilities. Although some predisposing factors are the same as those found in younger women, older women have additional physiological and anatomical risk factors that contribute to the development of UTIs. These differences must be taken into consideration when selecting management strategies. The use of indwelling catheters, poor functional status, and underlying medical conditions in residents of long-term care facilities contribute to an increased risk for UTIs. Antimicrobial therapy for uncomplicated UTIs is similar to that in young women, but complicated UTIs require longer courses of therapy and correction of underlying predisposing factors when feasible.

EPIDEMIOLOGY
Asymptomatic bacteriuria is the most common bacterial urinary tract problem.1 Among women older than 65 years, asymptomatic bacteriuria is found in 17-33% of those residing in the community, 23-27% of those living in residential homes, and up to 55% of those who are residents of long-term care facilities.2,3 Several longitudinal studies performed in community-dwelling older women have noted that bacteriuria frequently develops in those who are not initially colonized and that many women who are initially bacteriuric clear their urine of bacteria without any intervention.4,5

Symptomatic UTIs occur less commonly; in contrast to asymptomatic bacteriuria, only a few longitudinal studies using stringent criteria for the diagnosis of infection have been reported. Rates of symptomatic UTIs have varied from 0.9 per 1000 days among older women in the community,6 to 1-2.4 per 1000 resident-days in women residing in a long-term care facility.7 Among a group of community-dwelling women with bacteriuria followed for 6 months, the risk of developing symptomatic UTI was noted to be 16%.8 There are undoubtedly a larger number of infections among residents of long-term care facilities, many of whom are not symptomatic with infection. At the same time, UTIs represent the major source of sepsis within this patient population.

PATHOGENESIS
The pathogenesis of UTIs in older women includes those factors that are prominent in younger women—sexual activity and the genetically determined presence of receptors on uroepithelial cells that permits colonization by certain strains of E. coli.9 Women with a history of recurrent UTIs when they were young are more likely to have recurrent infections when they are older.10,11 Additionally, in older women, several other factors assume increased importance as determinants of risk. Incontinence and dysfunctional bladder emptying due to a variety of physiologic and anatomic factors, including cystoceles and prior urologic procedures, increase the risk for infection.11 In postmenopausal women, changes in the vaginal mucosa are associated with increased vaginal pH, disappearance of lactobacilli, increased vaginal and perineal colonization with uropathogenic E. coli, and increased risk of UTIs.12 In women residing in long-term care facilities, the use of indwelling catheters greatly increases the risk for UTI.13

MICROBIOLOGY
The most common cause of UTIs in older women living in the community is E. coli, accounting for 60-70% of infections.14 Other gram-negative bacilli, including Proteus mirabilis and Klebsiella pneumoniae, are more likely to cause infection in older women than in younger women. Staphylococcus saprophyticus, the second most common pathogen in young women, is rarely seen in older women, but enterococci, rare in young women, are associated with a small portion of infections in older women.10 E. coli remains the most common pathogen overall. Women who reside in long-term care facilities are at risk for infections associated with anti-microbial-resistant bacteria including Pseudomonas aeruginosa, Providencia stuartii, and Citrobacter species.3

CLINICAL MANIFESTATIONS
Healthy older women living in the community are more likely than those residing in long-term care facilities to exhibit dysuria, frequency, and urgency with lower UTI, and fever, nausea, and costovertebral angle pain and tenderness with pyelonephritis. However, even in community-dwelling older women, pyelonephritis is frequently misdiagnosed as pneumonia, gastroenteritis, or a nondefined febrile illness.15,16 Those with underlying medical problems—especially those in long-term care facilities—often have few symptoms associated with UTI. Increasing problems with incontinence, cognitive decline, and decreased functional status may be prominent findings among residents of long-term care facilities. The frequent admonition that foul-smelling urine indicates infection has been shown to be not helpful for diagnosis.17

DIAGNOSIS
Urinalysis remains an easy and useful screening test to establish the presence or absence of pyuria and bacteriuria. Although the presence of pyuria is helpful in the diagnosis of infection in young women, it is less useful in older women.18 Pyuria, without symptoms suggesting infection, increases with increasing age. Patients with asymptomatic bacteriuria often have pyuria, and those with indwelling urethral catheters routinely have pyuria.10,18,19 Thus, pyuria alone is not a reliable diagnostic finding of infection in older patients.

For older women with uncomplicated UTIs, a urine culture may not be necessary. However, cultures should always be obtained in patients with complicated infections including recurrent infection, treatment failures, and infections in hospitalized or institutionalized patients.20 The urine should be collected by the midstream, clean-catch technique. If this cannot be ensured, sterile catheterization of the bladder is appropriate. A positive culture implies only that bacteria are present in the urine, which occurs with both asymptomatic bacteriuria and infection. Quantitation can be helpful in that greater than 100,000 colony-forming units (CFU)/mL are unlikely due to contamination. However, quantitation will not differentiate asymptomatic bacteriuria from infection. Patients with infection due to enterococci may have lower colony counts, and for those with symptoms suggesting pyelonephritis, greater than 10,000 CFU/mL is accepted as indicative of infection.10

In the absence of definitive diagnostic tests for infection, clinicians should rely on the presence of symptoms suggesting infection. Patients who are asymptomatic—and especially those with indwelling urethral catheters—should not have surveillance cultures of urine performed. Bacteriuria is expected in catheterized patients, and should not be treated unless symptoms of UTI occur.

TREATMENT
Asymptomatic bacteriuria
In general, patients with asymptomatic bacteriuria should not be treated with antimicrobial agents. Several studies have affirmed that patients with asymptomatic bacteriuria do not have worse outcomes than those without bacteriuria.17,21-24 Additional reasons to not treat include the selection for increasingly resistant bacteria and the cost and side effects of antimicrobials.

Uncomplicated UTIs
Many infections that occur in healthy, community-dwelling, sexually active older women are uncomplicated, and treatment regimens are similar to those used in young women. For women believed to have lower UTI, recommendations for initial therapy include double-strength trimethoprim-sulfamethoxazole (TMP-SMX) twice daily for 3-7 days, a fluoroquinolone such as ciprofloxacin 250 mg twice daily or levofloxacin 250 mg every day for 3-7 days, or nitrofurantoin 100 mg 4 times daily/100 mg twice daily (sustained-release) for 7 days (Table I).25,26 A 3-day regimen is probably effective for many older women,25,27 but few data are available in this population and some authorities recommend 7 days of therapy.10 Single-dose therapy should not be used.

Increasing resistance to TMP-SMX has been noted in some geographic areas;26,28 however, TMP-SMX remains the drug of choice for most uncomplicated UTIs in patients who can tolerate this agent. Patients receiving warfarin or phenytoin should not be treated with TMP-SMX because of significant drug-drug interactions (Table II). If resistance among E. coli reaches 15-20% in a given geographic area, a fluoroquinolone or nitrofurantoin should be considered as first-line agents.26 Drawbacks to fluoroquinolones include higher cost as well as concerns about the development of fluoroquinolone resistance in other organisms.29 Resistance remains low for nitrofurantoin, but 4-times-daily dosing makes this agent less attractive. A twice-daily, sustained-release formulation for nitrofurantoin is available, but it carries a higher cost. Nitrofurantoin should never be used in patients with a creatinine clearance of less than 40 mL/min.

Patients believed to have upper tract infection should receive 14 days of antimicrobial therapy.30 A fluoroquinolone is recommended as the first-line agent for pyelonephritis, but TMP-SMX or ceftriaxone are also appropriate (Table I). Patients who are vomiting, appear ill, or have serious underlying diseases should be hospitalized to receive intravenous antimicrobial therapy and other supportive therapies. After stabilization, most of these patients can be discharged home on oral agents to finish a 2-week course. Women who have uncomplicated pyelonephritis and who are not toxic or vomiting can be treated with oral antimicrobials for the entire course if close follow-up can be ensured. At least one study that included older women in addition to young women demonstrated that initial therapy with oral ciprofloxacin was as efficacious as intravenous ciprofloxacin.31 Although 7 days of ciprofloxacin has been shown to be as efficacious as 14 days of TMP-SMX for pyelonephritis, the studies exclude postmenopausal women, those with diabetes mellitus, and those with urologic abnormalities.32

Complicated UTIs
Many UTIs experienced by older women are complicated by the presence of structural abnormalities, stones, or underlying diseases such as diabetes mellitus or stroke that lead to voiding difficulties.18,33 Treatment should never be shortened in this group, and follow-up urine cultures should be performed to ensure eradication. These patients are more likely to have enterococci and resistant gram-negative bacilli, especially if they have had prior UTIs treated with antimicrobials and if they reside in a long-term care facility. Initial therapy in patients who require hospitalization could include a broad-spectrum penicillin such as piperacillin-tazobactam. More than 30% of E. coli are ampicillin-resistant, making ampicillin-sulbactam less appropriate for initial therapy. After susceptibilities of the infecting organisms are complete, the simplest and least toxic regimen should be substituted to complete treatment for 14 days.

SPECIAL SITUATIONS
Recurrent UTIs
Older women who have recurrent UTIs, usually defined as more than three infections per year, are of special concern. In women who are sexually active and who have no symptoms suggesting abnormal voiding patterns, full urologic evaluation is probably not necessary unless persistent hematuria is noted. However, in women who are not sexually active and in those with voiding abnormalities, evaluation for predisposing factors should be performed. These women should undergo a thorough pelvic exam and measurement of post-void residual urine volumes. Urodynamic testing and cystoscopy may also be helpful in certain patients.11

Many times, no anatomic or physiologic abnormality is found other than changes in the vaginal mucosa, which can predispose to increased colonization with gram-negative bacilli (including E. coli) and subsequent UTIs. In these patients, correction of the vaginal changes with intravaginal estriol cream can decrease recurrences.34

In certain situations, prophylactic antibiotics can help prevent recurrent UTIs. Generally, prophylaxis can be stopped after 6-12 months. Although many patients will have no further infections, some will have recurrence of infection and may require a longer trial of prophylaxis. The regimen usually recommended is TMP-SMX, one-half of a single-strength tablet nightly or after sexual intercourse.30,35 Other regimens include daily trimethoprim 100 mg or a fluoroquinolone. Extended prophylaxis with nitrofurantoin should be avoided because of the risk of pulmonary fibrosis.

Interest in natural and herbal remedies has burgeoned in recent years. Preparations containing ingredients such as rose hips, colloidal silver, D-mannose, pink grapefruit oil, and combinations of herbs are marketed for the prevention of UTIs. Although efficacy data are limited, drug interactions are described and present a major concern.

A natural product that has been studied is cranberry juice. Cranberry juice helps prevent recurrent infections by interfering with the adherence of E. coli to uroepithelium.36 A double-blind, placebo-controlled trial in older women showed that the group receiving cranberry juice (10 oz/day for 6 months) had fewer episodes of bacteriuria and pyuria than controls.37 Antimicrobial use in the treatment group was half of that noted in the control group. One problem with this regimen is the large amount of sugar contained in cranberry juice, which poses a particular problem for persons with diabetes. Another study compared cranberry juice, cranberry tablets, and placebo, suggesting that both tablets and juice decrease the number of symptomatic UTIs.38 Although the absolute benefits of cranberry products are unclear, there does not appear to be significant risk to their use.

Patients with renal failure
Patients with renal failure must have the dosage of those antibiotics that are excreted through the kidney reduced to appropriate levels to avoid toxicity. In addition, treatment of UTIs can be accomplished only with those antimicrobial agents that achieve adequate levels in the urine. Fluoroquinolones, most penicillins, and TMP-SMX can be used, but aminoglycosides are generally ineffective and problematic because of their renal toxicity.33 Nitrofurantoin should not be used in patients with decreased renal function (creatinine clearance