Key points

Introduction

Both urinary tract infection (UTI) and asymptomatic bacteriuria (ASB) are common among elderly adults and represent a significant health care burden. UTIs are responsible for 15.5% of infectious disease hospitalizations in adults aged 65 or older, second only to pneumonia, and they are responsible for 6.2% of infectious disease-related deaths. Despite their frequency, differentiating between ASB and true UTI remains controversial among health care providers. In light of emerging antibiotic-resistant pathogens, this distinction has become increasingly important, because although symptomatic UTI requires appropriate antibiotic therapy, ASB does not.

Introduction

Both urinary tract infection (UTI) and asymptomatic bacteriuria (ASB) are common among elderly adults and represent a significant health care burden. UTIs are responsible for 15.5% of infectious disease hospitalizations in adults aged 65 or older, second only to pneumonia, and they are responsible for 6.2% of infectious disease-related deaths. Despite their frequency, differentiating between ASB and true UTI remains controversial among health care providers. In light of emerging antibiotic-resistant pathogens, this distinction has become increasingly important, because although symptomatic UTI requires appropriate antibiotic therapy, ASB does not.

Purpose of this review

This article will review proposed definitions of ASB and UTI, highlight emerging research in causes and prevention of bacteriuria and UTI in the elderly, and examine improvements in patient outcomes over the past 20 years with improved practice guidelines. The authors’ search criteria for the literature review utilized the PubMed database with the following key words: urinary tract infection, asymptomatic bacteriuria, bacteriuria, urinary tract microflora, urinary tract infection treatment, urinary tract infection risk factors, and combinations thereof. For inclusion, papers must have been published after 1980 and written in English. Exclusion criteria included foreign journal articles not translated to English.

Definitions of asymptomatic bacteriuria

As defined by the Infectious Disease Society of America (IDSA), ASB is the presence of 10ˆ5 colony-forming units per milliliter (CFU/mL) or more of 1 bacterial species in 2 consecutive urine specimens in women, or a single urine specimen in men, in the absence of clinical signs and symptoms of UTI. A single specimen containing greater than or equal to 10ˆ5 CFU/mL of a bacteria species is sufficient when obtained by catheterization in both men and women.

Definitions of urinary tract infection

For the purpose of this article, UTI means infection localized anywhere along the urinary tract, manifesting as cystitis, pyelonephritis, or prostatitis. Despite several consensus guidelines proposed by various interest groups in recent years, a concise definition of UTI and associated symptoms does not exist. Conserved criteria typically include pyuria as evidenced by presence of leukocyte esterase or white blood cells on urinalysis, symptoms attributable to the urinary tract, and a urine culture confirming a pathogenic source. Of these components, what constitutes urinary tract symptoms is most variable. Typical symptoms include fever greater than 38 C or chills, dysuria, frequency, urgency, new-onset or worsening incontinence, and suprapubic or flank pain. Clinicians often include lethargy, confusion, or a change in baseline function, but this can be particularly difficult to assess in complicated patients with baseline impaired cognition or extensive comorbidities.

Challenges and controversy in diagnosis

Several challenges exist in the evaluation of urinary symptoms in the elderly patient. Symptoms of UTI are highly variable, often nonspecific to infection, and can be difficult to assess in patients with limited communication abilities or poor baseline function. Additionally, problems are frequently encountered in the collection, testing, and interpretation of urine specimens. Urine specimens should be obtained midstream by clean catch, or by in-and-out catheter when controlled voiding or cooperation is problematic. Chronic indwelling catheters should be removed and a new catheter inserted prior to obtaining samples, as biofilm is ubiquitous to long-term catheters. However, explanation and adherence to these collection standards are lacking. A prospective observational study by Pallin and colleagues examined emergency department cases at a major academic hospital that included urinalysis as part of their evaluation. By postencounter interview, it was found that 57% of the 137 participants received no instruction on urine collection, and that only 6% of participants had in fact used proper midstream clean-catch technique. Improper collection leads to specimen contamination by normal genitourinary flora, increasing the likelihood of false-positive urinalysis or misinterpretation of normal flora as pathogenic infection.

Results of urinalysis are often misinterpreted and mishandled. Pyuria, for example, can be a useful laboratory component in making the diagnosis of UTI but can also lead clinicians astray. Although absence of pyuria has strong negative predictive value for ASB or UTI, presence of pyuria is poorly specific for clinically significant infection. Pyuria may be present in up to 45% of chronically disabled or incontinent adults, and in up to 90% of institutionalized adults, regardless of colonization or infection status. A retrospective review of 339 cases from 2 academic centers found that pyuria was present in 70% of cases of UTI and 42.3% of cases of ASB, but was associated with inappropriate antimicrobial treatment by an odds ratio of 3.27 (95% confidence interval [CI], 1.49–7.18). Specimens that do demonstrate pyuria should reflexively be sent for urine culture for confirm presence of a pathogen, but this step remains a common struggle in many health care institutions. In the observation study by Pallin and colleagues, only 59% of samples with positive urinalysis were sent for urine culture, but again positive urinalysis regardless of symptoms was associated with antibiotic treatment by an odds ratio of 4.9 (95% CI, 1.7–14). These findings highlight the necessity of skilled history taking, examination, and complete diagnostic urine testing for the appropriate treatment of elderly patients.

Epidemiology

Microbiology

Although some differences in common urinary tract pathogen prevalence are noted, Escherichia coli remains the most commonly cultured organism in both community-dwelling and institutionalized adults. Studies examining community-dwelling women report E coli isolates in 75% to 82% of positive urine culture, with the majority of remaining cultures attributed to Klebsiella, Proteus mirabilis and enterococcus. Similar organisms are responsible for both ASB and UTI in institutionalized adults. Two large cohort studies of long-term care residents found E coli to be the most common urinary isolate, accounting for 54.6% to 69% of positive cultures. One study found enterobacteriaceae species to account for 34.8% of remaining cultures, while the second distributed these between Klebsiella (12%) and Enterococcus faecalis (8%). Other common hospital-associated pathogens like Pseudomonas aeruginosa, vancomycin-resistant enterococci, and Candida spp have been identified in this population as well.

Patients with indwelling catheters are uniquely at higher risk for biofilm-associated organisms, polymicrobial infections, and yeast colonization and infection. Large epidemiologic studies in both Europe and North America show that E coli remains the most common cause of both ASB, accounting for 21.4% of positive cultures, and UTI, accounting for 31% to 35.3% of positive cultures in this population. Indwelling catheters are uniquely associated with biofilm organisms, making colonization and infection by P mirabilis, P stuarti, and P aeruginosa significantly more common. Candida spp are also particularly common in these patients, accounting for 12.9% of catheter-associated UTI by some estimates.

Risk factors

Many genetic, behavioral, and comorbid host factors have been speculated as risk factors for both ASB and UTI. Some of these represent modifiable behavioral factors, while others are more inherent to the patients overall health. Multiple studies support a history of UTI as a primary risk factor for future infection, conveying as high as a fourfold to sevenfold risk compared with patients who have never had a symptomatic UTI. This, combined with the growing understanding of uropathogen virulence and patient genetic variations, seems to imply that a certain percent of the population is inherently more susceptible to UTIs. Comorbid conditions including diabetes, dementia, incontinence, and iron deficiency anemia have all been described as independent risk factors for ASB and UTI.

In premenopausal women, lactobacilli predominate the vaginal flora and are responsible for the relatively acidic pH of the vagina. This acidic environment is lost in postmenopausal women, and is implicated in the increased colonization and infection by E coli and enterococcus species. Sexual activity has been associated with UTI in postmenopausal women, particularly within a 2 week period after activity, although this association is less robust than in premenopausal counterparts.

In men, benign prostatic hypertrophy has been established as a risk factor for UTI. Although it is reasonable to presume this association is a product of urinary stasis, the relationship may in fact be more complicated. Interestingly, a cross-sectional study by Truzzi and colleagues of 196 healthy participants found an association between bacteriuria and postvoid residuals greater than 180 mL in men, but this association has not been reproducible in ambulatory postmenopausal women

Pathophysiology

Our understanding of urinary tract colonization and infection has greatly expanded over the past decade, and substantial new evidence has highlighted the complicated interplay between protective host factors and pathogen virulence factors that determine the likelihood of infection. In the disease-free state, the urinary mucosa acts as a protective barrier from infectious attacks. Certain bacteria can evade this protective function by binding specific mucosal receptors, which in turn may initiate a rapid inflammatory response by the host. For example, P-fimbriated E coli , responsible for the majority of symptomatic UTIs, bind a glycosphingolipid receptor on the mucosal surface, triggering various inflammatory cascades, engaging submucosal tissue, and in some cases, leading to direct invasion of deeper tissues and the blood stream.

It is now being suggested that what differentiates ASB from symptomatic infection is not necessarily the virulence factors of the invading bacteria, but a combination of virulence factors and the inherent genetic makeup and immune response of the host. Multiple mouse studies have correlated various genetic variations with decreased initial inflammatory responses, and therefore increased likelihood of ASB. Similar findings have been mirrored in human studies. Specific TLR4 mutations have been associated with ASB in children, while other polymorphisms of the same receptor seem to protect from recurrent cystitis in adults. On the other hand, genes that exaggerate host inflammatory responses or blunt antimicrobial efforts are associated with decreased bacterial clearance, and more severe bladder and kidney infection. In both mice and human studies, polymorphisms of IRF3, a component of interferon signaling, have been associated with a majority of subjects. This concept was further highlighted by Marschall and colleagues, in a prospective cohort study demonstrating that while patient comorbidities could be correlated to presence of ASB, none of 12 E. coli virulence genes tested could be associated with likelihood of ASB.

The human microbiota and its complicated, symbiotic role in maintaining health have gained substantial attention throughout many disciplines over recent years. It is now being suggested that the healthy urinary tract is not a sterile environment, but in fact is populated by a dynamic set of microorganisms that change throughout time based on environmental and behavioral factors. Routine culture media are designed to produce common uropathogens but do not support the growth of many slow-growing, fastidious, or anaerobic organisms. However, advanced detection technologies have shown many other microbiota in the urinary tract of healthy adults, bringing to question the role of bacteria outside the context of disease. A recent review by Whiteside and colleagues reports multiple genera including Jonquetella, Parvimonas, Proteiniphilum, and saccharofermentas in the urinary tract of healthy patients over age 70, through polymerase chain reaction (PCR) and detection of 16s rRNA subunits. A study by Santiago-Rodriguez and colleagues also demonstrated viral communities in 20 individuals, including bacteriophages and low-risk or novel strains of human papiloma virus, but flora components were unassociated with history of urinary tract health. Although the exact role of these symbiotic organisms is still poorly understood, it is postulated that their metabolic byproducts may convey antimicrobial advantages and contribute to urinary health.