The urine is normally free of bacteria. Bacteriuria indicates the presence of bacteria in the urine. Bacteriuria can be symptomatic or asymptomatic. Pyuria is the presence of white blood cells in the urine and, when seen in conjunction with bacteriuria, is indicative of a true infection. Asymptomatic bacteriuria (ASB) is the isolation of bacteria from the urine in significant quantities consistent with infection, but without the local or systemic genitourinary signs or symptoms. The presence of ASB in the absence of symptoms or pyuria is often referred to as colonization. Cystitis refers to the symptoms of dysuria, urgency, frequency, and/or suprapubic pain. Infection (bacterial cystitis) is only one of many causes of this symptomatology, but one which is generally easy to prove or disprove with a simple urine culture.

Other important definitions include:

2. Suppressive antimicrobial therapy: Prevention of a clinically symptomatic infection in an asymptomatic patient whose urinary tract is colonized with bacteria.

3. Nosocomial urinary tract infection (UTI): Those that occur in hospitalized or institutionalized patients.

Urinary tract infections (UTIs) can be classified as to their site of origin. Cystitis refers to the nonspecific clinical syndrome of dysuria, urinary frequency, urgency, and suprapubic pressure. Fever, chills, and flank pain can indicate the presence of pyelonephritis, an interstitial inflammation caused by bacterial infection of the renal parenchyma. Surprisingly, based on symptoms, it can be remarkably difficult to differentiate infection involving the upper tracts from bacteriuria confined to the bladder. Many patients with pure lower tract symptoms will have positive cultures of renal pelvic and ureteral urine if catheterization of the upper tracts is performed. Conversely, some patients with flank pain will be found to have only cystitis on differential urine cultures. Fortunately, from a practical standpoint, it is not generally an important distinction, and localizing the site of infection in clinically uncomplicated infections is unnecessary.

UTIs can also be classified in terms of the anatomic or functional status of the urinary tract and the overall health of the patient. An uncomplicated infection indicates it is occurring in an otherwise normal urinary tract in a healthy individual. A complicated infection is one occurring in a functionally or structurally abnormal urinary tract, in a host with a compromised immune system, or an infection with bacteria of increased virulence or antimicrobial resistance (i.e., nosocomial UTI).

Perhaps the most useful classification of UTI for the primary care provider is that devised by Tom Stamey of Stanford University and based on the relationship of UTI episodes with each other. First infections refer to isolated or remotely occurring bacterial cystitis. These are the most common infections in women, occurring in 25% to 30% of women between the ages of 30 and 40 years. Unresolved bacteriuria occurs when the urine cannot be sterilized despite antibiotic treatment. Common causes include preexisting or acquired bacterial resistance, inadequate coverage of a second organism, rapid reinfection with a new organism during therapy, azotemia preventing access of the antibiotic to the urinary tract, and noncompliance with treatment. Recurrent infection is an infection diagnosed after successful treatment of an antecedent infection. This category represents 95% of recurrent UTIs in women. The other 5% may be caused by bacterial persistence. In this category, sterilization of the urine is short-lived, and within weeks, a relapse with the identical organism occurs. Such infections indicate a site of persistent infection within the urinary tract that could be a manifestation of an infected staghorn calculus, enterovesical fistula, or infected anatomic anomaly such as a diverticulum in the urinary tract.

UTIs are considered to be the most common bacterial infection. They are generally associated with minimal morbidity except among specific subpopulations. Eleven percent of women report having had a UTI during any given year, and more than half of all women have had at least one UTI in their lifetime. One in three women have a UTI before the age of 24 years. This contrasts with men, in whom infection is uncommon until after the age of 50 when the problem of an enlarged prostate and outlet obstruction may occur. Between 3.5 and 7 million office visits a year are the result of UTI, and direct costs exceed $1.6 billion. It is difficult to assess the true incidence of UTI because urine cultures are not often done in the outpatient setting, and symptoms are variable.

Symptomatic UTI is especially common among sexually active women. Modifiable behavioral risk factors include the use of a diaphragm and spermicides for contraception and frequency of sexual intercourse among premenopausal women. Estrogen deficiency is another risk factor, as is antimicrobial use itself. In women with a first UTI, 24% will have a second episode within 6 months, and up to half of women will have a second infection within a year. The risk of recurrent uncomplicated bacterial cystitis remains unchanged whether the initial episode is left untreated to clear spontaneously, or treated with short-term, long-term, or prophylactic antimicrobial therapy. Symptomatic episodes in the healthy population are more of a nuisance than a threat to health. No association between recurrent infections and renal scarring, hypertension, or renal failure has been established in patients with uncomplicated, simple recurrent UTI.

ASB is present in 3% of women in their early 20s, rising from 1% with the onset of intercourse in the late teenage years. It increases 1% per decade. The incidence of ASB in the pregnant population is similar to the nonpregnant population, but the implications are more concerning. The risk during pregnancy for pyelonephritis is increased substantially in those harboring bacteria in the urinary tract, especially during the end of the second and beginning of the third trimester. Studies suggest a 20% to 40% incidence of pyelonephritis if ASB is untreated in this population.

Diabetes increases the risk of UTI and bacteriuria among female but not male patients. UTIs in ambulatory patients with diabetes are considered complicated, with a heightened risk for pyelonephritis and severe complications if left untreated. UTI is more common in the multiple sclerosis population and can herald acute exacerbations and progression of the disease. Approximately 11% to 25% of elderly, noncatheterized patients can develop transient ASB, and persistent colonization in the elderly may affect up to 50% of geriatric women and be extremely difficult to eradicate.

The paradigm of uncomplicated UTIs is that bacterial virulence appears to be crucial for overcoming normal host defenses. With complicated UTI, the paradigm is reversed, in that bacterial virulence is much less important, and host factors tend to be critical.

The bacteria responsible for UTIs are normally present in the bowel. Escherichia coli is the most common, accounting for 85% of community-acquired infections and up to 50% of nosocomial infections. New research from Kylie Mansfield in Wollongong, Australia, suggests that the specific serotype of the lipopolysaccharide of the E. coli cell wall may determine whether or not ATP is released from the urothelium when it is stretched, resulting in either clinical cystitis or just asymptomatic colonization. Other common organisms include Proteus sp., Klebsiella sp., Enterococcus faecalis, and Staphylococcus saprophyticus. The female urethra is short, and bacteria generally enter the bladder in an ascending fashion.

Vaginal mucosal introital colonization generally precedes infection and is determined by bacterial adherence, the receptive characteristics of the epithelial surface, and the fluid that bathes both surfaces. Estrogens and pH affect attachment and colonization of the vaginal mucosa. Host defense mechanisms include the antiadherence properties of the vaginal and bladder mucosa, the hydrokinetic clearance of bacteria through voiding, and changes in urine pH and composition that may inhibit bacterial growth. Women with recurrent UTIs demonstrate increased adherence of bacteria in vitro to uroepithelial cells when compared to findings in women who have never had an infection. Studies suggest that this may be genetically determined.

Kunin has found strong statistical evidence that the female urethra has a powerful antimicrobial defense mechanism that appears to differ in women with and without recurrent UTI. The female urethra is lined by cells identical to those of the vagina that respond readily to estrogens. The normally functioning urethra may help to protect the bladder from cystitis through the shedding of uropathogens bound to exfoliating urethral cells; trapping of bacteria by mucus secreted by the paraurethral glands; intermittent washout by urine, local production of immunoglobulins, cytokines and defensins; and mobilization of leukocytes.

It is generally believed that some failure with the host defense mechanism allows for colonization of the introitus and vaginal mucosa in women subject to recurrent bacterial infection from reinfection outside the urinary tract. While colonized, these women can experience repeated infections for 6-12 months or more, each readily treated with antibiotics, but recurring within weeks or months. This introital colonization is of limited duration, and may resolve after 1 or 2 years and leave the patient asymptomatic until the next episode of colonization when subsequent bouts of infection begin.

Recent research by Gregory Anderson, Scott Hultgren, and colleagues at Washington University in St. Louis has demonstrated a new and possibly important mechanism by which E. coli can seed the bladder urine in the absence of introital colonization. They have shown in animal models that bacteria can subvert the innate host defense responses by invasion into the bladder superficial cells. Intracellular bacteria mature into biofilms, creating podlike bulges on the bladder surface. Pods contain bacteria encased in a polysaccharide-rich matrix surrounded by a protective shell of uroplakin. This can provide an internal reservoir of bacteria capable of causing clinical bacterial cystitis.

S. saprophyticus and enterobacterial species adhere to uroepithelial cells through different adhesive mechanisms than E. coli. After attachment, Proteus spp., K. pneumoniae, and S. saprophyticus each produce urease, which catalyzes the hydrolysis of urea in urine and causes the release of ammonia and CO₂. This elevates the urinary pH and can lead to the formation of bladder or kidney stones.

Risk factors for UTI include sexual intercourse, use of a diaphragm or cervical cap, and spermicidal jelly, which can alter the normal vaginal flora. The ABO-blood group nonsecretor phenotype is at increased risk for vaginal colonization with uropathogenic bacteria. Urologic instrumentation, diabetes, and age-related changes in the elderly patient are also risk factors. Low estrogen levels allow vaginal pH to rise, resulting in a higher likelihood of vaginal colonization with E. coli. The use of oral contraceptive agents is unrelated. Personal hygiene habits are not generally related to recurrent UTI, and it is wise to assure patients that this represents a biologic phenomenon rather than a result of poor cleanliness.

The history is a critical component in the diagnosis of UTI. The diagnosis is often made on history alone. The probability of bacterial cystitis in a woman with dysuria, urinary frequency, or gross hematuria is about 50% in the primary care setting. Urethritis and vaginitis can also cause acute dysuria in women. Cystitis is usually caused by enteric gram-negative bacilli or S. saprophyticus. Urethritis is caused by Chlamydia trachomatis, Neisseria gonorrhoeae, or herpes simplex virus. Vaginitis is caused by candidal species or Trichomonas vaginalis. Pyuria is rare in vaginitis but common in urethritis and cystitis. A positive urine culture is usually present in bacterial cystitis. Symptoms of cystitis are usually severe and more acute than those in urethritis, which can be mild, gradual in onset, and include vaginal discharge.

Symptoms suggesting vaginitis such as vaginal irritation or discharge reduce the likelihood of a diagnosis of cystitis by 20%. Dysuria and frequency in the absence of vaginal discharge raise the probability of acute UTI to 90%. If the woman has a history of culture-documented bacterial cystitis and experiences similar symptoms, the chance of a true infection approaches 90%.

If a urine culture is performed, it should be a carefully collected, midstream specimen to decrease the likelihood of any vaginal contamination. Approximately one third of women with acute symptomatic cystitis caused by E. coli, S. saprophyticus, or Proteus sp. have colony counts of midstream urine specimens ranging from 10² to 10⁴ CFU/mL. Thus a pure culture in the presence of symptoms must be considered significant, regardless of colony count.