In 2010, urinary tract infection (UTI) was the sixth most common diagnosis in women age 15 to 64 years and the fourth most common diagnosis in women age 65 years and older presenting to the ED.¹ The self-reported annual incidence of UTI in women is 12%, and by the age of 32 years, half of all women report having had at least one UTI. Although younger women are more likely to be affected than men by a ratio of 35:1, the gender gap decreases to 2:1 by age 66, most likely due to prostatic hypertrophy and need for instrumentation in elderly men.² All age groups from neonates to the elderly are affected, carrying risks in special populations. ³ (See chapters 132, “Urinary Tract Infection in Infants and Children” and 99, “Comorbid Diseases in Pregnancy”).

UTIs can be grouped based on the anatomic site involved as well as patient characteristics. These classifications are important when determining treatment modalities.

ASYMPTOMATIC BACTERIURIA

Asymptomatic bacteriuria is the presence of >100,000 (>10⁵) colony-forming units (CFU)/mL of a single pathogen on two successive urine cultures in a patient without symptoms.⁴

Prevalence of asymptomatic bacteriuria is up to 10% in pregnant woman, 40% in male and 50% in female residents of nursing homes, and up to 100% in patients with indwelling catheters for more than 1 month. There is evidence to suggest that asymptomatic bacteriuria may provide some protection against symptomatic infection with invasive organisms in patients with indwelling catheters⁵ and in patients with recurrent UTIs.⁶ Treatment of asymptomatic bacteriuria is recommended only in pregnant woman (see chapter 99) and in patients immediately prior to invasive urinary procedures.⁴

URETHRITIS AND CYSTITIS

Infections of the lower urinary tract include urethritis and cystitis. Acute cystitis is an infection isolated to the bladder. Acute cystitis without coexisting pyelonephritis in otherwise healthy, nonpregnant young females with no obstruction is a benign illness with a 24% spontaneous cure rate; less than 1% of patients go on to develop pyelonephritis.⁷ Competent ureteral valves prevent ascent of the bacteria into the kidneys in most cases. The diagnostic criterion in acutely symptomatic patients is a positive urine culture of ≥10² to >10³ CFU/mL.⁸ Urethritis, commonly associated with sexually transmitted diseases, presents with similar symptoms but typically is associated with a vaginal discharge or irritation.

PYELONEPHRITIS

Pyelonephritis is an infection of the upper urinary tract. Acute pyelonephritis involves the renal parenchymal and pelvicalyceal system. Pyelonephritis is differentiated from cystitis primarily by clinical findings: a syndrome of flank pain or costovertebral angle tenderness, with or without fever, in the setting of a positive urine culture of 10⁵ CFU/mL, and frequently other systemic symptoms such as nausea or vomiting. Infections of the upper urinary tract can progress into three patterns of renal infection not commonly considered part of the UTI spectrum: acute bacterial nephritis, renal abscess, and emphysematous pyelonephritis. These diagnoses are made based on imaging studies performed in patients who have an inadequate or atypical response to treatment for presumed acute pyelonephritis.

UNCOMPLICATED URINARY TRACT INFECTION

Uncomplicated UTI is a UTI in a patient without structural or functional abnormalities within the urinary tract or kidney parenchyma, without relevant comorbidities that place the patient at risk for more serious adverse outcome, and not associated with GU tract instrumentation.^9,10 This classification is thus limited to young, healthy, nonpregnant women with normal anatomic and functioning urinary tracts. Women are more susceptible than men to UTI due to a shorter urethra for uropathogenic bacteria to ascend. The traditional diagnostic criterion dating from 1960 had been a positive urine culture of 10⁵ CFU/mL; however, in symptomatic patients, low-colony-count infections with ≥10² to 10³ CFU/mL are clinically valid.^8,9,10

COMPLICATED URINARY TRACT INFECTION

Complicated UTI is infection involving a functional or anatomically abnormal urinary tract or infection in the presence of comorbidities that place the patient at risk for more serious adverse outcomes.¹¹ Risk factors for complicated UTI, including UTI in males, are listed in Table 91-1.⁹ The diagnostic criterion is the isolation of 10⁵ CFU/mL of urine culture. Unfortunately, patients with complicated UTIs are a very heterogeneous group, and few clinical trials have been conducted to guide management. In general, patients in this group are more likely to be infected with resistant organisms.¹¹ Although older literature categorized pyelonephritis as a complicated UTI, current guidelines do not.^10,11,12 Uncomplicated pyelonephritis refers to the clinical syndrome of fever and flank pain or tenderness with or without vomiting in a patient with an anatomically normal urinary tract without comorbidities. However, the recommended management of patients with uncomplicated pyelonephritis is similar to recommendations for patients with complicated UTI and differs from the management of patients with uncomplicated cystitis (see “Treatment” later in the chapter).

RECURRENT URINARY TRACT INFECTION

Recurrent UTI is defined as two uncomplicated UTIs in 6 months or three or more uncomplicated UTIs in the preceding 12 months.^13,14 Recurrent UTIs can be classified into two different categories that affect treatment decisions: relapse and reinfection. Relapse of UTI is a recurrence of a UTI within 2 weeks of treatment completion caused by the same organism from a focus within the urinary system, and represents treatment failure. Reinfection is a recurrent UTI caused by a different bacterial isolate or by the previously isolated bacteria after a negative intervening culture or a period of 2 weeks between infections.¹³ Reinfection is more common than relapse. Behavioral factors can lead to increased risk for uncomplicated UTIs. The concentration of bacteria in the female bladder may increase 10-fold after sexual intercourse, whereas the use of a diaphragm and spermicide is also associated with recurrent UTI, probably because the spermicide enhances vaginal colonization with Escherichia coli.¹⁵

MICROBIOLOGY

UTIs typically arise from ascending infection from the urethra to the bladder, although hematogenous and lymphatic spread can occur. Uropathogenic organisms often have adhesins, fibrillae, or pili that allow the bacteria to adhere to and invade the uroepithelium.^15,16 E. coli remains the most common pathogen by a large margin (Table 91-2).

First reported in 1983, but with an increase since 2000,¹⁷ community-acquired extended-spectrum β-lactamase–producing E. coli has emerged as a small but growing source of antibiotic resistance, affecting approximately 4% to 6% of outpatients with UTI.^17,18 Emergence of this resistant isolate of E. coli has important implications for treatment (see “Treatment” later in the chapter)¹⁹ and can increase mortality in those affected.²⁰

Several anatomic, genetic, and age-related factors increase risks for bacterial invasion of the urinary tract. Select women have specific uroepithelial cell E. coli–binding glycolipids that promote fecal coliform colonization of the vagina.² In postmenopausal women, decreased estrogen has been associated with a conversion of vaginal flora from lactobacillus to E. coli and other Enterobacteriaceae.² Incomplete bladder emptying disrupts the bladder’s ability to eradicate bacteria from its mucosal surface, increasing its susceptibility to infection, especially in patients with neurogenic bladder, women with uterine prolapse, and men with prostate hypertrophy.

Clinical features of UTI vary by anatomic site involved and the patient’s risks for complicated UTI. Asymptomatic bacteriuria is a laboratory-based diagnosis (see “Pathophysiology and Definitions” discussed earlier).

URETHRITIS

In males, dysuria with a urethral discharge indicates urethritis (see chapter 149, “Sexually Transmitted Infections”). UTI is uncommon in healthy young adult males, but if the clinical diagnosis does not suggest urethritis or prostatitis in a male with dysuria, bacteriuria is likely due to UTI. In women, Chlamydia infection should be suspected in the following settings: a new sexual partner, a partner with urethritis, examination findings of cervicitis, or low-grade pyuria with no bacteria seen on urinalysis. Concurrent gonorrhea is common with Chlamydia infections.

CYSTITIS

Symptoms and signs of cystitis are frequency, urgency, hesitancy, suprapubic pain, visible (gross) hematuria, and/or suprapubic tenderness. The nature and severity of symptoms are determined by the etiologic organism(s), the portions of the urinary tract involved, and the patient’s ability to mount an immune and inflammatory response.¹² A history of vaginal discharge or irritation is more often associated with vaginitis, cervicitis, or pelvic inflammatory disease than with UTI. Fever is uncommon with simple cystitis.

PYELONEPHRITIS

Flank pain, costovertebral angle tenderness, or specific renal tenderness to deep palpation may be associated with cystitis because of referred pain. However, when these findings occur, especially in association with fever, chills, nausea, vomiting, or prostration, the clinical diagnosis is acute pyelonephritis. Patients with pyelonephritis may or may not have coexistent symptoms of cystitis. The presentation of pyelonephritis may be subtle, and it might be difficult to distinguish lower from upper UTI, especially in patients who do not experience pain normally (those with spinal cord injury), immunocompromised patients, and the aged. A missed diagnosis of cystitis is unlikely to lead to patient deterioration^7,9; in contrast, missed pyelonephritis could lead to untreated sepsis.

UROSEPSIS

Patients with urosepsis may or may not exhibit the symptoms listed above for cystitis or pyelonephritis. As graded by the European Section for Infections in Urology,^10,21 simple urosepsis presents with temperature change (>38°C or <36°C), rising heart rate (>90 beats/min), elevated respiratory rate (>20 breaths/min), and commonly leukocytosis. Severe urosepsis includes hypotension, and/or organ dysfunction, and/or hypoperfusion as evidenced by lactic acidosis, oliguria, or acute altered mental status. Uroseptic shock adds the criteria of hypotension or ongoing evidence of hypoperfusion despite adequate fluid resuscitation (see chapter 150, “Toxic Shock Syndromes”).

COMPLICATED URINARY TRACT INFECTION

For patients at risk for complicated UTI (Table 91-1), the clinical features and the classic presenting signs and symptoms of UTI may vary widely or be entirely absent. Fever, pain, and an inflammatory response may be absent. Suspect UTI in more complicated cases involving patients with atypical and diverse signs and symptoms, including weakness, malaise, altered mental status, fever, and flank or abdominal pain. Guidelines suggest the following criteria be used to define symptomatic catheter-associated UTI: new onset or worsening of fever, rigors, altered mental status, malaise, or lethargy with no other identified cause; flank pain; costovertebral angle tenderness; acute hematuria; pelvic discomfort; and in those whose catheters have been removed, dysuria, urgent or frequent urination, or suprapubic pain or tenderness.^22,23 In patients with spinal cord injury, increased spasticity, autonomic dysreflexia, and sense of unease are also compatible with catheter-associated UTI.²²

A definitive diagnosis of UTI combines appropriate historical findings with laboratory confirmation.^9,24 However, a clinical diagnosis of acute uncomplicated cystitis can be made with a moderate probability based on a history of dysuria, frequency, and urgency, in the absence of vaginal discharge or irritation, in women who have no other risk factors for complicated UTIs.¹⁰ However, the false-positive rate for the diagnosis of UTI based on history alone has been reported to be 33% in outpatients^24,25 and as high as 43% in ED patients. Although empiric treatment of uncomplicated cystitis based on history alone in select women continues to be advocated by some experts,¹⁰ three systematic reviews do not recommend history-based diagnosis due to inaccuracy,^26,27,28 and other authors advocate laboratory confirmation to reduce the growing problem of antibiotic resistance.^19,29,30

The clean-catch, midstream voiding specimen is as accurate as urine obtained by catheterization if the patient follows instructions carefully. If the sample is properly collected, it should contain no or few epithelial cells. Bacteria in urine double each hour at room temperature, so urine should be refrigerated if not sent directly to the laboratory. Catheterization is indicated if the patient cannot void spontaneously, is too ill or immobilized, or is extremely obese. Avoid unnecessary catheterization, because 1% to 2% of patients develop a UTI after a single catheter insertion.

Visual inspection or assessment of the odor of the urine is generally not helpful in determining infection because cloudiness and odor are caused by noninfectious etiologies. Table 91-3 lists normal reference values for urinalysis. UTI often results in positive dipstick test for protein in the urine, but this finding is not specific enough to be useful in diagnostic decision making to rule in infection.

Values for individual laboratories may differ from the listed norms in Table 91-3. Dipstick testing is performed on a fresh uncentrifuged urine specimen and is quick and easy to perform at the bedside. Urine for microscopic analysis is routinely centrifuged prior to analysis. If examination of uncentrifuged urine is desired, make a specific request to the laboratory to account for different normal values between centrifuged and uncentrifuged specimens.

NITRITE REACTION BY DIPSTICK TEST

The urine nitrite reaction has a very high specificity (>90%), and a positive result is very useful in confirming the diagnosis of a UTI caused by bacteria that convert nitrates to nitrite, primarily the coliform bacteria, including E. coli. Enterococcus, Pseudomonas, and Acinetobacter species do not convert nitrates to nitrites in the urine and therefore are not detected by the nitrite test. Unfortunately the urine nitrite reaction has a low sensitivity (~50%), so it is not always useful as a screening examination because a negative result does not exclude the diagnosis of UTI.

LEUKOCYTE ESTERASE REACTION BY DIPSTICK TEST

Using positive culture results as the criterion standard, the leukocyte esterase urine dipstick test has an overall sensitivity of 48% to 86% and a specificity of 17% to 93% for identifying infection. Performance varies by clinical setting. In the ED, using culture findings of 10⁵ CFU/mL as the criterion, a positive leukocyte esterase reaction result has a sensitivity of 77% and a specificity of 54%. The sensitivity of positive leukocyte esterase reaction result for detecting infection decreases for specimens with less bacterial growth at culture, ranging from a sensitivity of 79.5% when culture growth is >10⁵ CFU/mL to 50.4% when culture growth is 10³ CFU/mL. Therefore, if the clinician uses a lower culture threshold to define infection, the leukocyte esterase test performs with lower sensitivity to detect infection. In summary, a positive urinary dipstick nitrite or leukocyte esterase test result supports the diagnosis of UTI, but a negative test result does not exclude it.

URINE WBC COUNT OR PYURIA BY MICROSCOPY

The assessment of pyuria using standard centrifuged urine is imperfect due to variable specimen preparation techniques. A WBC count of >5 cells/high-power field (HPF) in a centrifuged specimen from a symptomatic patient is abnormal. Although the combination of pyuria and bacteriuria is likely to be found with typical coliform infection, lower degrees of pyuria with or without bacteriuria may be clinically significant, especially in the presence of UTI symptoms.

In a symptomatic patient who has <5 WBCs/HPF in a centrifuged specimen, other causes of false-negative pyuria should be considered such as dilute precentrifuged urine, systemic leukopenia, or patient self-treatment with leftover antibiotics. Pyuria may be intermittent or absent if the patient has an obstructed and infected kidney. In men, >1 or 2 WBCs/HPF in a centrifuged specimen can be significant when bacteria are present. Urethritis and prostatitis are far more likely causes of pyuria in young males who are sexually active and complain of dysuria, regardless of the presence or absence of urethral discharge.

BACTERIURIA BY MICROSCOPY

Bacteriuria is a sensitive tool for detection of UTI in the symptomatic patient. The presence of any bacteria on a Gram-stained specimen of uncentrifuged urine (>1 bacterium/HPF or 1000×) is significant and highly correlates with culture results of >10⁵ CFU/mL. For Gram-stained centrifuged specimens, >1 bacterium/HPF (1000×) is 95% sensitive and >60% specific to predict a culture with 10⁴ CFU/mL. Both of these methods of looking for bacteria under the microscope fail to detect low-colony-count UTI or infection caused by Chlamydia. False-positive results can occur when vaginal or fecal contamination is present. Female patients with symptoms suggestive of UTI and vaginal discharge or dyspareunia should have a pelvic examination to investigate for pelvic inflammatory disease.

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