Symptomatic urinary tract infections and asymptomatic bacteriuria in elderly women can be frequently encountered in outpatient clinics, how to diagnose, treat, prevent and manage urinary tract infections in elderly women in the community?On February 26, 2014, JAMA conducted a review on urinary tract infections in elderly women, and the main contents are compiled below.
I. Case report
Mrs. M, 91 years old, lives with her partner in a retirement community. She has a past history of coronary heart disease, hyperlipidemia, hypertension, diabetes mellitus, cerebrovascular disease and hypothyroidism. Recently, she presented to Dr. N with increased chronic urinary frequency and incontinence. Her urinary tract infection started in her college days and in the last few years she has developed urinary incontinence. Currently, she has frequent urination (every 2-3 hours) and nocturia (waking up once every 2 hours).
In 2008, her fluid intake was limited to 1 cup for dinner, as prescribed by her primary care physician, followed by drinking only the amount of medication she was taking. Over the past few months, her urinary frequency and incontinence have worsened. Recently, she has started using adult diapers. She is still sexually active. There is no dysuria or hematuria and no dizziness or lightheadedness.
Previous treatment with oxybutynin and tolterodine was ineffective in treating overactive bladder, and meprobamate and sofranexin improved symptoms transiently. The use of these drugs has been discontinued. Urinary incontinence worsened and a urine culture was required. Previous 6 urine cultures were positive for E. coli, >105 colony forming units/mL. Multiple courses of antibiotics have not improved the symptoms of urinary incontinence.
Overview of urinary tract infection
1. Recommended approach to the evaluation and treatment of urinary tract infections in elderly women
Bacterial infections are the most common type of urinary tract infection, with more than 8 million outpatients and 1 million emergency room visits and approximately 100,000 patients requiring hospitalization in the United States each year. Women of all ages are approximately twice as likely as men to be seen in outpatient urinary tract infections.
A urinary tract infection (UTI) is defined as an infection of the urinary system that may involve the lower or upper and lower urinary tract. Asymptomatic bacteriuria, symptomatic urinary tract infections, and sepsis-associated urinary tract infections all required hospitalization (Table 1).
Asymptomatic bacteriuria is defined as the absence of any symptoms or signs of urinary tract infection and a urine culture colony (same urinary tract pathogen) count of ≥105 CFU/ml on 2 consecutive clean midstream urines. asymptomatic bacteriuria is a state of colonization and does not require treatment.
Diagnosis of symptomatic urinary tract infection requires that the patient has signs and symptoms of urinary tract infection, as well as laboratory tests (≥105 CFU/mL for bacteriuria and ≥10 leukocytes/high magnification field for pus urine).
Simple symptomatic urinary tract infection with bladder infection presenting with fever without known cause, increased urinary urgency or frequency, pus urine, pressure pain in the suprapubic area, pressure or percussion pain in the cribriform angle, and laboratory tests suggestive of urinary tract infection. Fever is usually absent when the symptoms of urinary tract infection are confined to the bladder.
Complex urinary tract infections are defined as symptomatic urinary tract infections caused by functional or structural abnormalities, previous urinary tract instrumentation, systemic systemic disease such as renal insufficiency, diabetes mellitus or immunodeficiency, or organ transplantation. Pusuria is the presence of white blood cells in the urine.
The high prevalence of chronic genitourinary symptoms, which can increase cognitive impairment and comorbidities with increasing age, continues to make the management and treatment of symptomatic urinary tract infections a challenge.
In the case described above, Mrs. M had several risk factors for symptomatic urinary tract infections: postmenopause, urinary incontinence, history of symptomatic urinary tract infections, and sexual activity. Some evidence suggests that recurrent urinary tract infections may be associated with genetic factors. Diabetes mellitus is also an important risk factor for recurrent urinary tract infections in women.
Recurrent urinary tract infections with the same or different uropathogens are common in outpatients, leading to repeat visits, increased treatment or prophylactic use of antimicrobials, and patient anxiety and depression.M Mrs. M has only exacerbation of urinary frequency symptoms without other urinary tract infection-specific symptoms and therefore does not meet the diagnostic criteria for symptomatic urinary tract infection.
The exacerbation of chronic urinary incontinence could be due to the use of continuous diuretics or the natural progression of the incontinence course. The fact that antibacterial drugs did not improve Mrs. M’s incontinence symptoms also suggests that her urinary tract infection should not be classified as a symptomatic urinary tract infection.
III. Diagnosis, treatment and prevention
1. Clinical presentation and diagnosis of asymptomatic bacteriuria and symptomatic urinary tract infection in the elderly
Asymptomatic bacteriuria is common, and its incidence increases with age. It is 3.5% in the general population, increasing to 16%-18% in women older than 70 years, and some longitudinal studies have reported that it affects 50% of older women. In this population, it is generally benign at the beginning.
Sterile or aseptic older adults tend to have specific genitourinary symptoms, including increased urinary urgency, urinary incontinence, difficulty urinating, and nonspecific symptoms – such as loss of appetite, malaise, lethargy, and weakness as experienced by Mrs. M in the case report.
In a longitudinal prospective study of ambulatory older adults, the bacterial phenotype of urine samples obtained at 6-month intervals suggested that more than 30% of patients with bacteriuria were self-limiting, and another 30% were initially free of bacteriuria and subsequently progressed to bacteriuria (Table 2). In elderly people with chronic incontinence and limited mobility, 45% may have pusuria (≥10 leukocytes) and 43% have bacteriuria (≥105 CFU/ml). Women with asymptomatic bacteriuria with pus urine also met the laboratory criteria for symptomatic urinary tract infections, but not the clinical criteria for symptomatic urinary tract infections because they lacked signs and symptoms of urinary tract infections.
As for Mrs. M, chronic urinary incontinence makes it difficult to distinguish between symptomatic urinary tract infections (with the possibility of causing urinary tract infection or pyelonephritis) and asymptomatic bacteriuria (benign ones). Hematuria aseptic and pus urine may not be associated with infection. The incidence of genitourinary symptoms is higher in older adults, and the evaluation of symptomatic urinary tract infections in older women in most studies requires both physical signs and symptoms of urinary tract infection (≥2 genitourinary signs and symptoms), plus laboratory confirmation of urinary tract infection (bacteriuria and pusuria), to establish a diagnosis of urinary tract infection in older patients.
Urinary urgency and incontinence are present in older women even in the absence of urinary tract infections. Chronic difficulty in urination is also common and worsens with age. Several recent studies, by defining the validity of clinical features of urinary tract infections and laboratory evidence of urinary tract infections, have provided guidelines for use in differentiating asymptomatic bacteriuria from symptomatic urinary tract infections.
Significant correlations were found between laboratory-confirmed urinary tract infections and acute voiding difficulties, changes in urinary characteristics, and altered mental status in older adults in social welfare facilities. Of these clinical features, acute dyspareunia (duration < 1 week) was the most effective predictor of laboratory-confirmed urinary tract infections.
In a Spanish epidemiological study of 343 women aged 14-90 years, the pretest probability of new-onset urinary symptoms in patients with urinary tract infection was 0.48, and the positive likelihood ratios for new-onset dyspareunia, urgency, and frequency were 1.31, 1.29, and 1.16, respectively. this study reinforces the concept that new-onset dyspareunia is the most discriminatory clinical manifestation of symptomatic urinary tract infection.
When assessing new-onset dyspareunia, timing, severity, and localization are important. Both urinary tract infections and urinary incontinence can occur with increased frequency or urgency of urination. Therefore, a diagnosis of urinary tract infection based on these symptoms alone is not reliable. In contrast, new-onset dyspareunia is specific for symptomatic urinary tract infections and, if present, suggests the need for further diagnostic evaluation.
In elderly female patients with a high incidence of asymptomatic bacteriuria and progressive worsening incontinence, the diagnosis of symptomatic urinary tract infection still requires evaluation of emerging signs and genitourinary symptoms and consideration of other diagnoses. There is no clear answer to how to assess urinary urgency. Although urinary tract infections are a serious problem, some randomized controlled studies have found that 25%-50% of women with symptoms of urinary tract infection recover within 1 week without the use of antimicrobial drugs.
Spontaneous improvement of symptoms occurred in 50% of community-dwelling non-intubated female patients who delayed antimicrobial therapy (Table 2). Therefore, when assessed for symptomatic urinary tract infections, delaying antimicrobial therapy generally does not result in adverse outcomes. Symptoms such as dizziness and confusion cannot be attributed to urinary tract infection.
A clinical situation similar to Mrs. M’s is likely to have been treated with hydration in addition to antimicrobial therapy during hospitalization, and restoration of hydration status resulted in improvement of clinical symptoms. In women with urinary urgency, they are often asked to restrict fluid intake, leading to dehydration. Therefore, when the diagnosis of symptomatic urinary tract infection is in doubt, antimicrobial therapy should be delayed in favor of further evaluation and consideration of supportive therapy, such as increased fluid intake (Table 2).
Principles of urinary tract infection detection and treatment
2. The role of urine testing in the diagnosis of symptomatic urinary tract infections in the elderly
The use of urine test strips, urinalysis and culture can be challenging in elderly patients because of the high incidence of bacteriuria and pusuria, but may not be clinically significant. As for the case of Mrs. M, all urine tests assessing leukocyte esterase, nitrite, pusuria, and bacteriuria were positive over a 2-year period.
Urine test strips, although simple and convenient, are fickle in nature. The sensitivity and specificity of urine test strips tests to assess changes in leukocyte esterase, nitrite, or both in older adults was assessed by the age of the study population, clinical suspicion of urinary tract infection, and laboratory definition for the use of urinary tract infection (bacteriuria alone – bacteriuria levels > 102-105 CFU/ml, or bacteriuria plus pus urine).
The sensitivity and specificity of positive urine test strips in elderly patients were 82% and 71%, respectively. Other studies in elderly patients have shown a range of 92%-100% negative predictive values for paper testing. Urine test paper analysis should be performed on an outpatient basis, primarily to rule out rather than establish a diagnosis of urinary tract infection.
Patients with a low pretest probability of urinary tract infection who test negative for leukocyte esterase and nitrite test strips rule out the presence of infection and reduce the need to obtain urine and urine cultures (Table 3). The high false-positive rate limits the validity of the test paper test. Further urine testing is necessary for the high pretest probability of urinary tract infection in patients with urinary tract infections.
On the basis of clean laboratory urine collection, the presence of pus urine is confirmed if at least 10 leukocytes per high-powered view, the urine culture is positive (≥105 CFU/mL biologic colony formation), and the urine culture confirms the presence of pathogenic bacteria.
In the outpatient setting, urine specimens should be collected cleanly by the patient. In female patients, the labia should be separated and the urethral area cleaned by wiping from front to back using an antibacterial soap solution prior to urination. The initial urine stream should be discharged into the toilet or potty, catching the midstream urine into a sterile container. If the patient does not have easy access to clean collected urine specimens (e.g., obesity, arthritis), routine specimens, although less desirable, can be used.
3. When to send urine for testing
When to send urine to the laboratory for testing in the clinical management of elderly patients with chronic nonspecific symptoms is somewhat difficult. Because of the high prevalence of asymptomatic bacteriuria in older women, the pre-test probability of positive urine or urine bacterial culture testing is high. A variety of complications can lead to urinary symptoms (e.g., urinary urgency, frequency, and difficulty urinating). In a study of elderly patients complaining of poor health (anorexia, difficulty staying asleep, weakness, lethargy, fatigue, and debility), the presence of bacteria was found to be absent in urine with frequent incontinence. Therefore, when there is chronic nocturia, urinary incontinence, or lack of well-being in a general sense, urine should not be routinely sent for testing.
Urinalysis should be performed when there is fever, acute dyspareunia (duration < 1 week), new or worsening urgency, urinary frequency, new incontinence, hematuria, and percussion pain or pressure in the suprapubic area or cribriform angle. Acute dyspareunia is more useful to identify urinary tract infections and other genitourinary symptoms (Figure).
In patients with cognitive impairment, persistent altered mental status and changes in urinary characteristics that do not respond to other interventions (i.e., hydration) suggest the need for urinalysis. Given the known recurrence of bacteriuria in elderly patients, urine testing should not be performed after treatment of urinary tract infections. Evaluation of clinical outcomes should be based on improvement in symptoms without the need for repeat urine testing. The figure below depicts a clinical line of care that, although not clinically validated, can be applied to the treatment of elderly patients.
4. Principles of treatment for the elderly
Some studies have shown that treatment of asymptomatic bacteriuria does eradicate urinary bacteria. However, reinfection rates, side effects of antimicrobial drugs and increasing isolation of drug-resistant bacteria were more common in the treated group than in the non-treated group. There was no difference in genitourinary morbidity or mortality between the treated and non-treated groups.
For the past three decades, infection physicians have opposed screening or treatment of asymptomatic bacteriuria in community or welfare-dwelling older adults. However, geriatrics and the primary caregivers of the elderly have consistently insisted on determining the presence of nonspecific changes that may be associated with urinary tract infections.
In patients with dementia, 75% of patients with urinary tract infections are not satisfied with the minimum standard of initial antibiotic therapy received, but still receive antibiotics. Two important issues need to be considered when treating urinary tract infections in elderly patients: the choice of antibiotic and the course of therapy.
The choice of antibiotic should be guided by the bacterial pathogen (if known), the local resistance rate, the spectrum of adverse effects, and the patient’s comorbidities. Among community-dwelling older women, the predominant causative organisms are Escherichia coli (51.4%), Klebsiella pneumoniae (4.1%), Aspergillus chimaera (3.3%), and Enterococcus faecalis (2.5%).
Resistance rates are variable, but outpatient urinary isolates are more resistant in the United States than in Canada. fluoroquinolone resistance is highest in elderly patients 65 years and older. Fluoroquinolones are the most commonly used antibiotics in outpatient clinics today. from 2005 to 2009, the resistance rate of fluoroquinolone E. coli isolates increased from 464 to 1116 per 100,000 person-years in outpatients aged >80 years. The rate of fluoroquinolone plus cotrimoxazole resistance in E. coli isolates increased from 274 to 512 per 100,000 person-years.
Broad-spectrum β-lactamase-producing Gram-negative bacteria were associated with community-acquired acute simple urinary tract infections. These bacteria had high rates of resistance to oral antimicrobials, including amoxicillin-clavulanic acid (69.6% resistant), ciprofloxacin (84.8% resistant), and cotrimoxazole (75.9% resistant). Furantoin (15% resistant) and fosfomycin (0% resistant) remain effective in the treatment of these bacterial infections.
A 3-day cotrimoxazole is recommended as standard treatment for urinary tract infections. Fluoroquinolones are only recommended as first-line empiric therapy in communities where methotrexate-sulfamethoxazole resistance rates are greater than 10-20%. Despite these recommendations, the use of cotrimoxazole has not changed significantly, while the use of ciprofloxacin has increased. Current guidelines continue to recommend cotrimoxazole as first-line empiric therapy for patients with community-living resistance rates of less than 20%.
Recently, revised guidelines include furantoin as one of the first-line drugs for the treatment of urinary tract infections. However, the FDA states that a contraindication to this drug is a patient’s creatinine clearance of <60 mL/min/1.73m2. This evidence of contraindication is limited and is based on a patient's inadequate furantoin concentration with a urinary creatinine clearance of less than <60 mL/min/1.73m2.
Recent evidence suggests that furantoin, can be safely used in patients with creatinine clearance ≤40 mL/min/1.73m2. Furantoin achieves very low plasma concentrations, 40% of which are excreted in the urine, maintains a very low resistance rate after 60 years of use, and it is relatively low cost. Furantoin should be considered for the treatment of cystitis in the elderly only. Furantoin can have pulmonary toxicity. Patients receiving this drug should be evaluated promptly when they develop new pulmonary symptoms.
Because of the presence of highly resistant strains, fosfomycin may be effective in the elderly. But it is more expensive than other oral medications. Vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and ultra broad-spectrum beta-lactamase (ESBL) gram-negative rods are usually susceptible to fosfomycin, and although its antimicrobial effect is lower than that of other first-line drugs, it is an attractive oral agent for the selection of resistant strains in outpatients.
In addition, when all oral agents are unavailable, short courses of outpatient intravenous antibiotic therapy are another viable option that can be administered without hospitalization.
The optimal course of treatment for the elderly is unknown. A recent review of 15 studies (1644 years old women) showed no difference in short- to medium-term clinical failure between short-course (3-6 days) and long-course (7-14 days) oral antibiotic therapy. Monotherapy was preferred in most patients compared to short-course therapy, but with a higher rate of persistent urinary tract infections.
Treatment options for outpatients with mono-urethral infections
5. Ongoing management of urinary tract infections
Repeated urine testing is not necessary in elderly patients. In patients with recurrent symptomatic urinary tract infections (Table 1), long-term use of antimicrobials should be considered, with 6-12 months of application effective in reducing urinary tract infection episodes.
Furantoin 50 mg/day given to elderly patients had minimal adverse effects and was not resistant after 1 year of treatment. Six months of methotrexate (40 mg/200 mg /d), methotrexate (100 mg /d), and furantoin (100 mg /d) are also effective, but sulfadoxine-resistant E. coli strains are common in patients treated with methotrexate-based chemotherapy regimens.
Treatment process of urinary tract infection in elderly women
IV. Prevention
Recent studies on postmenopausal women have shown a higher incidence of symptomatic urinary tract infections due to sexual activity, suggesting that post-sexual symptomatic urinary tract infections can occur in older women. It is therefore necessary to ask older women about their recent sexual status. Sexually transmitted infections can cause urinary tract symptoms, and if the presence of vaginal discharge is present, an evaluation for sexually transmitted infections should be performed.
As for younger women, early urination after sexual intercourse and free intake of appropriate fluids during the day are recommended. In addition, prophylactic application of antimicrobial drugs can prevent urinary tract infections in young women and may be considered after sex.
A study in older women showed that a 300-ml cranberry juice cocktail reduced laboratory evidence of urinary tract infections at 6 months. Subsequent studies have produced conflicting results, in part due to inadequate cranberry standardization of the active ingredient. The available evidence suggests that cranberry is effective in reducing the risk of urinary tract infections in middle-aged and older women with a history of recurrent urinary tract infections (Table 4).
Oral estrogen therapy has still not been found to be effective in reducing the risk of urinary tract infections compared with placebo; however, vaginal estrogen cream reduced urinary tract infections in 2 studies.
Evaluation of medications leading to urinary retention and urinary evaluation for conditions predisposing to urinary tract infection, such as pelvic organ prolapse, bladder lesions, or kidney stones, should be performed before initiating these prevention strategies.
Prevention of urinary tract infections
V. Summary
Asymptomatic bacteriuria, urinary incontinence, and symptomatic urinary tract infections are common in older women, and determining which patients require antibiotic therapy is difficult.
Establishing a diagnosis of symptomatic urinary tract infection requires careful clinical evaluation, urinalysis and laboratory evaluation of urine cultures. New-onset dyspareunia is one of the best indicators of a potentially symptomatic urinary tract infection.
The incidence of genitourinary symptoms is higher in older adults and urine should be tested if there is no other identifiable cause and the patient’s symptoms worsen dramatically. Nonspecific symptoms such as a general lack of well-being should not be the only reason for urine testing.
Once the diagnosis of symptomatic urinary tract infection has been established, antimicrobial drugs should be selected through a previously understood susceptibility profile of uropathogens, taking into account the possible side effects of the antimicrobial drugs, potential interactions with other drugs, and the patient’s comorbidities.