Introduction

Urinary tract infection (UTI) is the most common type of infection in women. Recent estimates indicate that evaluation and treatment of urinary tract infections result in $1.6 billion in direct costs annually in the United States. The most common infectious agent associated with UTIs is Escherichia coli. Risk factors include sexual activity, spermicide use, prior UTI, urinary obstruction, and congenital anomalies of the urinary tract. In women with typical symptoms, empiric treatment may be initiated without the need for an office visit or laboratory evaluation. Nitrofurantoin, trimethoprim-sulfamethoxazole, fluoroquinolones, and β-lactams have been shown to be effective in the treatment of UTIs. Prophylaxis should be considered in women with recurrent infections. Special considerations should be given to pregnant women, postmenopausal women, and women with diabetes mellitus or indwelling catheters who develop UTIs.

Scope of the problem

Urinary tract infections are important in women’s health because they are the most common bacterial infection.[1] Review of the 2009–2010 combined data of the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) estimates that UTIs account for an estimated 5.4 million primary care office visits annually and another 2.3 million emergency room visits annually.[2] Although most patients with UTIs are treated as outpatients, 16.7%, or approximately 110,000 annually, require hospitalization.[3] Recent estimates are that evaluation and treatment of UTIs result in $1.6 billion in direct costs annually in the United States.[3]

Definitions

“Bacteriuria” is defined as the presence of 10⁵ colony-forming units of bacteria per milliliter of urine collected from midstream urine on two consecutive urinations.[4] When a patient has bacteriuria but no associated symptoms, she is diagnosed with asymptomatic bacteriuria. This is particularly important in pregnant patients and will be discussed in detail later in the chapter.

Symptomatic infection of the urinary tract is a UTI and may involve the urethra, bladder, ureters, and/or kidneys.[5] Infections of the lower tract (bladder and urethra) are commonly referred to as cystitis; whereas, infections of the upper tract (kidney and ureters) are referred to as pyelonephritis.

The vast majority of UTIs are uncomplicated and do not progress to more serious infections; these are referred to as uncomplicated UTIs. On the other hand, patients who are pregnant, have chronic medical conditions (e.g., diabetes, neurogenic bladder, immunosuppression, or renal insufficiency), urinary obstruction, or calculi and who present with UTIs are considered to have complicated UTIs.[6] As seen later in the chapter, UTIs in these patients have implications for both length of treatment and empirical antibiotic treatment choice.

A final important differentiation is between recurrent and resistant UTIs. Resistant UTIs are those that fail to demonstrate resolution of bacteriuria following 7–14 days of appropriate antibiotic treatment.[7] Recurrent UTIs are defined as a subsequent UTI following successful treatment of an initial UTI in a six-month period of time or at least three UTIs within a year.[5]

Pathophysiology

Urinary tract pathogens reside as normal flora in the bowel. Prior to the development of a UTI, these bacteria colonize the vagina and/or urethra. The bacteria may subsequently spread to the urethra and then ascend to the bladder. Men are thus less likely than women to develop UTIs. The distance between the anus and the opening of the urethra is significantly greater in men. The tissue surrounding the opening of the urethra is dry in men; the moist environment in women facilitates both bacterial migration and growth. Moreover, the urethra is longer in men than in women.[8]

Vaginal colonization appears to be an important step in the development of UTI in most women. Colonization is more likely in women with changes in the normal vaginal flora and specifically lactobacilli.[9] Additionally, in some women pathologic bacteria are able to adhere more readily to the vaginal mucosa. Research has demonstrated that these women are more likely to develop recurrent UTIs.[10]

Once bacteria have entered the bladder, the organisms must adhere to the epithelium of the bladder. In pathogenic bacteria, particularly E. coli, adhesive organelles called Type 1 pili have a terminal molecule, FimH, which binds to the uroepithelium.[11] The bacteria can then invade the epithelial cells and begin to replicate, ultimately forming biofilms.[12] These biofilms are able to resist the host defenses of white blood cell influx and shedding of the bladder epithelium.[12]

The virulence of the uropathogenic bacteria is enhanced by the presence of a variety of structural components that assist in decreasing the effectiveness of the body’s immune and inflammatory responses. These include the presence of fimbria, flagella, a polysaccharide coating, adhesins such as FimH, and siderophores.[13]

Proteus mirabilis produces a urease that converts urea to ammonia and leads to precipitation of struvite and apatite crystals around the bacteria. These crystals provide a defense for P. mirabilis against antibiotics and can serve as a nidus for growth of other bacteria as well. Therefore, in patients with known calculi and symptoms of UTI, P. mirabilis infection should be strongly considered even if the culture does not grow out the species. Likewise, when urinary cultures grow Proteus, the patient should be evaluated for the presence of urinary calculi.[14]

Epidemiology/risk factors

Urinary tract infections are more common in women than men, with NAMCS and NHAMCS data demonstrating that 84% occur in women.[3] Furthermore, the infections occur with increased frequency in sexually active women.[15] In women over the age of 18, 10.8% report at least one UTI annually, and it is estimated that by age 24, one in three women will have at least one UTI requiring treatment.[16] Over the course of their lifetimes, women have an approximately 60% risk of having at least one UTI.[16]

Both modifiable and nonmodifiable factors have been associated with an increased risk of recurrent UTI. Several studies have demonstrated that specific blood group phenotypes (Lewis nonsecretors in particular) have higher rates of UTI secondary to increased adherence of bacteria to the epithelial cells.[17] Additionally, other nonmodifiable risk factors include a prior history of UTI, urinary obstruction, and congenital anomalies of the urinary tract.[15, 18] Furthermore, at least one study identified an increased risk of UTI in women whose mother had a history of UTI.[19]

Modifiable risk factors include those related to contraceptive use (spermicides, spermicide-coated condoms, and oral contraceptives) and those related to frequency of intercourse (≥4 times/month).[19] Spermicides increase the risk for UTI by allowing increased growth of E. coli following alteration of normal vaginal flora.[20] A study of sexually active college women demonstrated that compared to women who had not had intercourse during the week, women who had had intercourse three times had a 2.6-fold increase in relative risk whereas women who had daily intercourse had a ninefold increase in relative risk of UTI development.[21] Data suggests that this increase in risk is related to both trauma to the urethra and the mechanical introduction of bacteria into the urethra.[22, 23]

Research has failed to show a relationship between voiding habits, personal hygiene practices, and beverage consumption and recurrent UTIs.[19]

History

Patients with uncomplicated lower tract UTIs will frequently describe dysuria (difficulty and/or pain with urination), frequency (decreased latency between episodes of urination often associated with small volumes of urination), and/or urgency (sensation that one has to urinate immediately). They may also report hematuria, pyuria, and suprapubic discomfort or pain. Patients with upper tract infections, in addition to the symptoms just mentioned, may report nausea, vomiting, fevers, chills, and flank pain.

Although dysuria is common in women with UTIs, it can also be seen in women with urethritis and vaginitis. Differentiation of the three potential etiologies may be possible based on concomitant symptoms and timeline of symptom development. UTIs are commonly associated with pyuria and hematuria, but only pyuria is seen in urethritis, and neither is typically seen in vaginitis. Symptoms in UTI are typically acute in onset and severe in nature, whereas symptoms in urethritis and vaginitis tend to be more gradual in onset and milder in nature. Furthermore, vaginitis is often associated with vaginal discharge, odor, and pruritus not seen in UTI or urethritis.[24]

History of previous UTI is important to assess, as is a history of any complicated UTI.

Medical and surgical history should focus on factors that would increase the risk of UTI in general and also complicated UTI. Such factors include pregnancy, diabetes, neurogenic bladder, immunosuppression, renal insufficiency, urinary obstruction, or history of calculi. A history of urogenital surgeries should be obtained.

Physical exam

In general, physical examination is not diagnostic in the evaluation of UTI. It may be useful in differentiating lower tract infections from upper tract infections as both fever and costovertebral angle tenderness are more consistent with upper tract infections.[25] Additionally, in patients with vague or unclear symptoms, pelvic examination may reveal a vaginal source of symptoms instead of a urinary source.

Laboratory

Urinalysis and urine culture are the gold standards of UTI diagnosis. Typically, women are instructed to provide a midstream urine sample for evaluation after cleansing the perineum with a bacterial wash and while spreading the labia to prevent contamination. The use of these three techniques in the collection of the urine is designed to minimize the risk of contamination of the sample with skin flora. One randomized controlled trial (RCT) has called these techniques into question demonstrating similar contamination rates (29% and 32%, respectively) in women who provided a nonmidstream urine sample without cleansing versus women who provided properly collected midstream urine.[26]

Urinalysis can confirm the presence of bacteriuria and pyuria in patients with UTI symptoms. Pyuria is commonly defined as the presence of 10 or more leukocytes per high-powered field when examining an unspun urine.[27] As noted earlier, bacteriuria is the presence of >10⁵ colony-forming units of bacteria per milliliter of urine.[4]

Urinalysis is frequently carried out with a dipstick instead of a microscope. Urine dipsticks evaluate for a combination of factors present in the urine including nitrite, leukocyte esterase, protein, glucose, ketones, hemoglobin, bilirubin, urobilinogen, acetone, pH, and specific gravity. A meta-analysis of studies looking at the sensitivity and specificity of the components of a urine dipstick used to diagnose UTI found that either a positive nitrite or leukocyte esterase are associated with a sensitivity of 75% and a specificity of 82%.[28] Individual studies have demonstrated sensitivities of 75%–96% and specificities of 94%–98% with a positive leukocyte esterase.[29]

Urine culture should be considered in all women who have symptoms consistent with pyelonephritis, women with both UTI symptoms and vaginal discharge, women with recurrent UTIs, and women with a history of resistant UTIs.[6, 30, 31]

Additionally, in patients with symptoms consistent with pyelonephritis or with comorbid conditions which increase the risk of sepsis (e.g., diabetes mellitus), blood cultures should be obtained.[32]

Radiology

The vast majority of UTIs do not require any form of radiologic imaging. If there is a concern about possible urocalculi, obstruction, or anatomic anomaly, imaging may be helpful. Although plain films can be useful in identifying a radiopaque stone, ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI) offer the ability to identify anatomic anomaly, hydronephrosis, abscess, and stones.[34] Indications for imaging our summarized in Table 35-2.

Treatment

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