Clinical Overview of Urinary Tract Infections

Background

Urinary tract infections (UTIs) are a major public health concern in the United States, affecting millions of people each year. UTIs occur when pathogens, particularly bacteria, enter the urinary system, leading to inflammation and infection. UTIs can involve the kidneys, bladder, ureters, or urethra, and they can affect people of all ages. Illness severity ranges from mild, uncomplicated infections to life-threatening sepsis of urinary origin.

Cause

Most UTIs result from bacterial infection. Escherichia coli (E. coli) causes 80-90% of cases.12 Certain strains of E. coli, known as extraintestinal pathogenic E. coli (ExPEC), can cause infections outside the gut. A subtype of ExPEC, urinary pathogenic E. coli (UPEC), is responsible for UTIs. Other bacteria that can cause UTIs include Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae complex, and Staphylococcus saprophyticus.

Types

UTIs can be categorized into several types based on the site of the infection within the urinary system. The main types include:

• Cystitis: An infection of the bladder. Symptoms include frequent urination, urgency, burning, and lower abdominal discomfort.
• Pyelonephritis: An infection of one or both kidneys. Symptoms may include fever, chills, flank pain, nausea, and vomiting. Patients may also have symptoms of cystitis.

Spectrum of UTIs

• Asymptomatic bacteriuria: The presence of bacteria in the urine without any accompanying symptoms. It is frequently identified during routine urine examinations; however, it generally does not necessitate treatment, except under specific circumstances. For example, pregnancy, where it is associated with increased risk for pyelonephritis, pre-term birth, and low birth weight leading to all pregnant women being recommended to undergo screening for asymptomatic bacteriuria at least once during early pregnancy.3
• Uncomplicated UTIs: Infection limited to the bladder in afebrile adults.4
• Complicated UTIs: Infections beyond the bladder including pyelonephritis, febrile or bacteremic UTI, catheter-associated urinary tract infections (CAUTI), or prostatitis.4
• Recurrent UTI: Certain individuals encounter multiple UTIs over time, which may be attributable to the same or different pathogens. Recurrent UTI refers to at least 2 infections in six months or at least 3 infections in one year. Recurrent UTIs can be uncomplicated or complicated.45

Related conditions

• Urethritis: An inflammation of the urethra; symptoms may include fever, pain during urination, and discharge from the urethra. If limited to the urethra, assess for infectious (e.g., chlamydia) and non-infectious causes (e.g., trauma).

• Prostatitis: An infection of the prostate gland in men, presenting symptoms similar to either cystitis or urethritis. There are four types of prostatitis: chronic prostatitis, also known as chronic pelvic pain syndrome, acute bacterial prostatitis, chronic bacterial prostatitis, and asymptomatic inflammatory prostatitis.

At-risk populations

UTIs can occur in people of all ages and sexes, in particular:

• Women of any age
• Pregnant women
• Elderly men
• Individuals with diabetes
• Catheter users
• Individuals with certain conditions, such as kidney stones, vesicoureteral reflux, and issues with bladder control

Risk factors

• Anatomical factors
  • Female anatomy: Women have a shorter urethra than men, which allows bacteria easier access to the bladder.
  • Urinary tract abnormalities: Structural abnormalities in the urinary tract can obstruct normal urine flow and increase the risk of infection.

• Sexual activity: Sexual intercourse can introduce bacteria from the genital area into the urethra

• Hormonal changes: During menopause, hormonal changes can bring about shifts in vaginal flora and lower estrogen levels, which may increase vulnerability to infection.

• Catheter use: Indwelling catheters or intermittent catheterization can introduce bacteria directly into the bladder

• Urinary retention: When conditions affect the complete emptying of the bladder, such as an enlarged prostate in men or specific neurological issues (e.g., neurogenic bladder), it can lead to stagnant urine. This creates an environment that allows bacteria to thrive.

• Diabetes: Individuals with diabetes may have weakened immune systems and elevated glucose levels in their urine, creating an environment conducive to bacterial growth.

• Immunocompromised state: An immunocompromised state due to conditions such as HIV/AIDS or medications like immunosuppressants increases susceptibility to infections.

• Personal hygiene practices: Poor hygiene practices (e.g., wiping from back to front after using the toilet) can allow bacteria to enter the urinary tract.

How it spreads

UTIs are typically caused by the introduction of bacteria into the urinary tract from external sources or from other areas of the body. Here are some common ways UTIs can develop:

• Ascending infection:
  • Urethra (urethritis) to Bladder (cystitis): The most common route for a UTI is through bacteria entering the urethra and ascending to the bladder.
  • Bladder to the kidney (pyelonephritis) via the ureters.
• Catheterization:
  • Indwelling catheters: Individuals who use indwelling urinary catheters (either short- or long-term) are at increased risk for catheter-associated UTIs because catheters can introduce bacteria directly into the bladder.
  • Intermittent catheterization: Even intermittent catheterization poses a risk, especially if proper sterile techniques are not adhered to.
• Spread from nearby organs: In some cases, bacteria may spread to the urinary tract from nearby organs, such as vesicovaginal fistulas and enterovesical fistulas (colovesical, rectovesical, ileovesical, and appendicovesical).
• Bloodstream Infection: Although infrequent, bacteria may infiltrate the urinary tract via the bloodstream in cases where an existing infection elsewhere, such as pneumonia or a skin infection, is present.

Disease burden and trends

UTIs are among the most common bacterial infections in the United States, affecting individuals across the lifespan. While UTIs are more prevalent in women, both sexes are impacted, with notable differences in incidence, severity, and outcomes by age and sex.

Although recent United States national estimates are lacking, data from various surveillance systems and studies, prior to COVID-19 pandemic, provide insight into the burden of UTIs:

• Emergency department (ED) visits: UTIs account for approximately 2.7 million ED visits annually.6
• Hospitalizations: Each year, an estimated 400,000 hospitalizations are attributed to UTIs as the principal diagnosis, with associated healthcare costs totaling approximately $2.8 billion. 7
• Complicated UTIs: The incidence of complicated UTIs is estimated at 1.01%, corresponding to roughly 2.88 million cases annually.8

Sex and age disparities

An estimated 50–80% of women will experience at least one UTI in their lifetime, and 30-40% will experience recurrent infections.9 Although less common in men, UTIs tend to be more severe in older males due to anatomical and functional abnormalities of the urinary tract.

Prevalence by age group

Using insurance claims databases,A among U.S. adults aged 18–64 years who presented to an outpatient setting with uncomplicated UTI during 2007–2016,B the prevalence in a given year was similar across age groups, ranging from 3.0% to 4.0% overall, and was higher among females than males in each group.10

Prevalence was:

• 3.8% among adults aged 18–24 years (range: 3.6%–4.0%),
• 3.6% among those aged 25–34 years (range: 3.0%–3.9%),
• 3.4% among those aged 35–44 years (range: 3.1%–3.6%),
• 3.3% among those aged 45–54 years (3.0%–3.5%),
• 3.8% among those aged 55–64 years (3.4%–4.0%).

For ages 65 and olderC

Prevalence was:

• 6.8% among adults aged 65–69 years (range: 6.6%–7.0%),
• 8.2% among those aged 70–74 years (range: 8.0%–8.4%),
• 10.0% among those aged 75–79 years (range: 9.6%–10.2%),
• 11.8% among those aged 80–84 years (11.2%–12.2%),
• 14.3% among those aged ≥85 years (13.5%–14.7%).

Economic impact

UTIs are associated with substantial health care costs in the United States, including direct costs such as outpatient visits, laboratory testing, medications, and hospitalizations, as well as indirect costs from productivity loss and complications due to recurrent infections.

Prior studies found that:

• Community-acquired UTIs are estimated to cost approximately $1.6 billion annually.11
• Complicated UTIs are associated with a median 30-day cost of approximately $2,000 per case, and more than $6 billion in annual expenditures.8
  
• Among Medicare beneficiaries with complicated UTI, total 30-day medical spending was estimated at $4.5 billion, with average spending of $6,181 per beneficiary. Acute care hospitalization was the main cost driver, with average spending of $15,438 per hospitalization.12

When pathogens such as carbapenem-resistant Acinetobacter, vancomycin-resistant Enterococci, multidrug-resistant Pseudomonas aeruginosa, extended-spectrum beta-lactamase (ESBL) Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae are antimicrobial-resistant, they increase the infection burden and add $138 million to $1.2 billion in excess healthcare costs annually.13

Testing

In healthy, premenopausal, non-pregnant women with classic symptoms, clinicians can often diagnose an uncomplicated UTI based on history and physical exam alone. When uncertainty exists, testing may include a urine sample, urinalysis, urine culture, or imaging. Other tests may include cystoscopy, blood culture, inflammatory markers, and elevated serum prostate-specific antigen (PSA) level to assess for prostatitis.141516

Patient management

Depending on the presentation, hospitalization may be required. Treat empirically.

• Antibiotics: Studies have demonstrated that antibiotic prescribing for UTIs is common and at times inappropriate, resulting in treatment failure.1718192021 Healthcare professionals must remain cognizant of the potential risk associated with infections caused by antimicrobial-resistant pathogens. Adherence to established clinical guidelines is recommended for the management of UTIs, as these guidelines are designed to optimize patient outcomes while minimizing unnecessary antibiotic use. 42214232425Antimicrobial resistance tends to increase with recurrent infections. Ongoing monitoring of patients with recurrent UTIs and reviewing antimicrobial susceptibility patterns is essential to inform effective treatment strategies.
• Pain Relief: Over-the-counter medications such as phenazopyridine may relieve discomfort but do not address the underlying infection.
• Additional measures might be required, such as frequent intermittent catheterization (which requires sterile technique), replacing an indwelling catheter, and consulting urology or other specialists such as urogynecology.
• Follow-up monitoring is not needed for uncomplicated cystitis. However, patients diagnosed with complicated UTIs should be closely monitored for potential treatment failure. Likewise, a patient exhibiting hematuria ought to undergo evaluation for persistent hematuria.
• Patients experiencing recurrent UTIs should be assessed for preventive strategies.

Long-term effects

While most UTIs can be effectively treated with antibiotics, recurrent or untreated UTIs can lead to several long-term effects and complications including:

• Recurrent infections: Some individuals may experience recurrences of UTIs, leading to chronic discomfort and the need for ongoing treatment. Repeated exposure to antibiotics can lead to the development of antimicrobial resistance and disruption of the gut microbiome26. This may also affect the vaginal microbiota.27
• Pyelonephritis: If a UTI spreads to the kidneys (pyelonephritis), it can cause permanent damage to kidney tissue, potentially leading to chronic kidney disease or renal scarring.
• Urosepsis: In severe cases, a UTI can lead to sepsis known as urosepsis, which requires immediate medical attention. Survivors of sepsis may experience long-term health issues related to impaired organ function and delayed overall recovery.2829 Genitourinary tract infections account for 16-37% of adult sepsis hospitalizations.30 Patients at increased risk for urosepsis include adults ages 65 and older, people with diabetes, immunosuppressed patients such as transplant recipients, cancer patients receiving chemotherapy or corticosteroids, and those with acquired immunodeficiency syndromes. Mortality rates for patients with sepsis of urinary origin range from 8% to 60%. 313233This clinical burden is further compounded by the growing challenge of antimicrobial resistance.
• Psychological effects: The stress and anxiety associated with recurrent infections or chronic symptoms can impact mental health, leading to feelings of frustration or depression in some individuals. Additionally, UTIs can affect quality of life.3435

Similar diseases

Several diseases and conditions can present symptoms like those of UTIs or may be related to the urinary system.

• Interstitial cystitis (IC): A chronic condition characterized by bladder pain, a sense of urgency, and an increased frequency of urination, occurring in the absence of an identifiable infection.
• Vaginitis: Inflammation of the vagina, leading to discomfort, itching, and abnormal discharge. Conditions such as bacterial vaginosis or yeast infections may present symptoms like those of a UTI.
• Kidney stones: Hard mineral and salt deposits form in the kidneys and can lead to intense pain (often occurring in waves), blood in the urine, nausea, and frequent urination.
• Bladder cancer: In its early stages, symptoms can resemble UTIs, including hematuria, a frequent need to urinate, and urgency even in the absence of infection.
• Diabetes-related conditions: Unmanaged diabetes may result in urinary problems, including frequent urination, as elevated blood sugar affects kidney function or leads to bladder dysfunction.
• Sexually transmitted infections (STIs): Some STIs can result in urethral irritation. Take a sexual history as part of routine healthcare when there are symptoms or physical exam findings suggestive of STIs.
• Fungal infections: Fungus such as Candida is commonly found in urine. It is often a sign of colonization or sample contamination, not always, infection. While less common, fungal infections due to opportunistic organisms like Cryptococcus and Aspergillus can involve the urinary tract, especially in individuals with weakened immune systems.36

Resources

• Urinary Tract Infections (UTI) | LTCF | NHSN | CDC
• Catheter-Associated Urinary Tract Infections (CAUTI) Prevention Guideline | Infection Control | CDC
• Antimicrobial Resistance Laboratory Networks | ARLN | CDC
• Emerging Infections Program | CDC
• Antibiotic Prescribing and Use | Antibiotic Prescribing and Use | CDC