Bacteriuria

Etiology

There are multiple ways for the urinary tract to become colonized or infected with bacteria. Typical patients who often colonize the urine are those older than 65 years of age or who have one of the following: chronic indwelling urinary catheters, neurogenic bladders, or a urinary stoma. Postmenopausal women may be at higher risk for colonization due to a loss of an acidic vaginal pH. Some individuals can begin colonizing with bacteria within 48 hours of urinary catheter placement. Common bacteria and fungi colonizers include Escherichia coli, Enterococcus species, and Candida species. Colonized patients may be asymptomatic, but some patients will become symptomatic due to an infection that must be treated. Women are more likely than men to develop UTIs as a result of their anatomy. E. coli is the most common pathogen associated with UTIs.[5][6][7][8]

Epidemiology

The occurrence of asymptomatic bacteriuria versus urinary tract infections varies among different patient populations. Younger, healthy individuals can have asymptomatic bacteriuria, but it is rare compared to older adults. The Infectious Diseases Society of America found a prevalence of 1% to 5% in healthy, premenopausal women and 1.9% to 9.5% in pregnant women. Increasing age is a risk factor, but prevalence is typically higher in females and those living in a long-term care facility (with or without a catheter). Women and men at least 70 years old were found to have a prevalence of 10.8% to 16% and 3.6% to 19%, respectively. Long-term care residents also had increased prevalence with 25% to 50% in women residents and 15% to 40% in male residents. Long-term use of indwelling urinary catheters is also associated with a 100% prevalence of asymptomatic bacteriuria, unlike short-term usage with up to 23% prevalence. Female diabetics have also shown an increased prevalence rate when compared to male diabetics, 9% to 27% versus 0.7% to 11%, respectively.

In regards to UTIs, women are more likely to develop them than men, although an increase is seen in men after the age of 50. Approximately 50% of women will develop at least one UTI within their lifetime, with 1 in 3 women having a UTI by the age of 24. In younger women, UTI recurrence is 25% within 6 months of the first occurrence. If pregnant women with asymptomatic bacteriuria are not treated, up to 40% will develop a UTI, but the actual incidence of UTIs in pregnancy is as low as 4%. UTIs are the second most common infection for all elderly individuals not in long-term care, accounting for 25% of all infections.  Individuals with indwelling urinary catheters are at higher risk of developing UTIs. The most common nosocomial infection in hospitals and nursing homes is catheter-associated urinary tract infections (CAUTIs).

Pathophysiology

Females frequently develop UTIs due to the urethra being close to the vagina and rectum, which can lead to the unintentional introduction of fecal flora into the urinary tract. The bacteria ascend from the urethra to the bladder in cystitis. If the bacteria ascend from the bladder via the ureters to the kidneys, then pyelonephritis develops. Pyelonephritis can also occur due to the seeding of the kidneys from bacteremia via the lymphatic system. When males develop UTIs, including prostatitis, it is usually due to an obstruction such as a urinary stone or enlarged prostate. The insertion of a chronic indwelling urinary catheter is also a risk factor for the development of UTIs. Organisms can be introduced into the urinary tract from a catheter via a patient's fecal or skin contaminants or healthcare personnel contact. Urinary catheters can lead to the growth of uropathogens by providing a site for adhesion in addition to disrupting normal host defenses.

History and Physical

Individuals with symptomatic bacteriuria from a lower UTI commonly present with frequency, urgency, dysuria, and suprapubic pain with a rapid onset over a 24-hour period. Elderly patients often present with mental status changes, although other reasons for confusion or delirium should be part of the differential diagnosis. There are also nonspecific symptoms that can occur, such as fatigue, irritability, malaise, nausea, headache, abdominal discomfort, and back pain. For those individuals presenting with an upper UTI, the symptoms mentioned above can still be identified in addition to fever and flank pain. Individuals with UTIs may present with cloudy, dark, bloody, or foul-smelling urine, but any one of these factors presented alone should not automatically determine a UTI diagnosis.

Evaluation

If an individual presents with urinary tract symptoms consistent with a UTI or if a patient presents with severe sepsis of unknown origin, then a UTI must be considered as part of the differential diagnosis. The urinalysis (UA) and urine culture are the most important laboratory findings used to determine if an individual has a UTI or not.  First, a UA must be evaluated to determine if the urinary white blood cells (WBC) and leukocyte esterase (LE) values are abnormally high, indicating pyuria and possible infection. Other abnormalities may be observed from a UA of an individual with a UTI, including a positive nitrite value.[6][9][10]

If the UA is considered significant for a UTI in a symptomatic patient without other reasons for the abnormal findings (e.g., the asymptomatic individual with chronic urinary catheter placement), then empiric antibiotic treatment should be started. Empirically treating a negative UA can be appropriate if the patient is neutropenic and determined to have a UTI based on other factors, including a significant number of organisms in the urine culture with signs and symptoms of an infection. When a UA is collected via a voided specimen, it is considered to be contaminated if there are more than 20 squamous cells under a microscopic high-power field, and the sample should be recollected before antibiotic initiation to determine if empiric therapy is truly indicated. If the UA finds elevated WBCs (more than 10) and LE (positive value), but the individual has a chronic indwelling catheter, additional consideration should be placed on ensuring the patient has clinical symptoms of a UTI before starting treatment. A chronic indwelling urinary catheter with bacteriuria may irritate the bladder wall resulting in pyuria without an actual infection.

Once the urine culture results are available, it should be determined if the colony-forming unit (CFU) per milliliter (mL) is considered significant for UTI versus possible contamination. In specimens collected from a voided specimen, greater than or equal to 100,000 CFU/mL is considered diagnostic for an individual who has a positive UA. There is more controversy with the CFU/mL cut-off in specimens collected from a urinary catheter, so signs and symptoms should be an even more important factor in the diagnostic evaluation. Technically, individuals with greater than or equal to 1000 CFU/mL from a catheter specimen can have a UTI. Since urine collected correctly from a catheter should contain fresh, uncontaminated urine, a lower threshold for CFU/mL is justified compared with voided specimens. If 3 or more organisms are identified in the cultured urine, this suggests that the specimen is contaminated.

Imaging studies are not routinely indicated in cystitis or acute uncomplicated pyelonephritis but can be helpful in certain scenarios. Individuals with persistent symptoms after 48 to 72 hours of appropriate antibiotic therapy should undergo evaluation of the upper urinary tract, as well as those pyelonephritis patients who appear severely ill. Computed tomography (CT) scanning without contrast is usually the imaging study of choice, but contrast is needed when renal perfusion studies are required. Since there are no clinical signs that can reliably differentiate simple acute pyelonephritis from a dangerous, obstructed pyonephrosis that requires urgent surgery, consider an imaging study if there is a history of kidney stones or clinical suspicion of a stone.

Treatment / Management

Adults determined to have asymptomatic bacteriuria should not typically be treated unless pregnant, undergoing a genitourinary procedure, or immunocompromised (e.g., neutropenic, possibly renal transplant). Before antibiotics are initiated in individuals with a known UTI, urinary catheter removal or exchange should occur if it was not previously completed prior to urine specimen collection. Multiple antibiotics are available for the treatment of UTIs. These include fluoroquinolones, sulfamethoxazole/trimethoprim, beta-lactams, and nitrofurantoin (the latter only indicated for cystitis).

Increasing bacterial resistance to commonly used oral antibiotics has increased the necessity of carefully reviewing culture susceptibility results. The resistance of commonly encountered UTI pathogens occurs not only in the inpatient setting but in outpatients as well. E. Coli and Klebsiella species are now becoming resistant via extended-spectrum beta-lactamase (ESBL) positive or Amp C producers. There are some exceptions, but these resistance mechanisms lead to in vivo clinical failures with all penicillins, cephalosporins, and monobactams. Carbapenems are typically the drug class of choice in these multi-drug-resistant pathogens.

Local antibiogram data should be reviewed to determine the best empiric therapy options for UTIs. This requires determining the best option for organisms such as E. Coli, Klebsiella species, and Proteus species. Preferably the susceptibility for a given organism should be 80% to 90% or higher from recent local urine susceptibility data. Empiric therapy should also be determined by an individual's allergies and any recent urinary cultures from the individual in case any multi-drug resistant organisms need to be covered.

Once an individual's culture susceptibility results are known, therapy should be modified to ensure an antibiotic with the narrowest spectrum to cover the organism(s) being treated is used while still obtaining appropriate penetration in the bladder and kidneys as necessary. If the patient also has a bloodstream infection due to the same organism as the UTI, a bactericidal antibiotic is preferred. It should have at least 90% oral bioavailability if an oral antibiotic is an appropriate option for both sites of infection. Any antibiotics requiring renal dosing should be evaluated based on the individual's creatinine clearance or estimated glomerular filtration rate. Once the antibiotic has been de-escalated appropriately, one additional step should be taken to ensure antimicrobial stewardship practices are implemented.

Healthcare providers should ensure that the duration of therapy is sufficient to eradicate the pathogen(s) but not excessively long to cause adverse events or resistance. Uncomplicated cystitis patients are typically treated from 3 to 7 days, depending on the antibiotic chosen. In uncomplicated pyelonephritis, therapy ranges from 5 to 14 days based on antibiotic therapy. In complicated cystitis and pyelonephritis, treatment can last as long as 7 to 14 days, depending on the individual circumstance. Of note, more studies continue to evaluate the shorter length of therapy for urinary infections.

Differential Diagnosis

• Acute pyelonephritis
• Bladder cancer
• Chlamydia (chlamydial genitourinary infections)
• Cystitis nonbacterial
• Emphysematous pyelonephritis
• Emphysematous cystitis
• Interstitial cystitis
• Pelvic inflammatory disease

Prognosis

Some women with recurrent UTIs that have been treated for asymptomatic bacteriuria have been found to have higher rates of symptomatic UTIs and a higher prevalence of antibiotic-resistant bacteria.

For most patients presenting with UTIs, the prognosis is good unless the individual develops severe sepsis. In severely septic patients, choosing the best antibiotic based on local susceptibility data from the antibiogram, the clinical history, and the individual patient's characteristics is vital to successful outcomes since the risk of mortality increases every hour without the correct antibiotic therapy. In addition, avoiding unnecessary treatment is also vital to successful outcomes.