Chapter 91: Urinary Tract Infections and Hematuria

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.

COMBINED RESULTS OF DIPSTICK TESTING, URINE CELL COUNTS, AND HISTORICAL INFORMATION

Two meta-analyses found that classic historical findings of cystitis were weak predictors of positive culture or failed to predict cystitis.^27,28 Vaginal discharge weakly decreased the likelihood of cystitis; however, in both studies, diagnostic accuracy was significantly improved using dipstick testing, particularly a positive test for nitrites.^27,28 A 2013 systematic review of four ED-based studies pooled 948 patients using a reference culture threshold of 10⁴ to 10⁵ CFU/mL and found that no single historical variable of cystitis could rule in or rule out infection, but a dipstick test positive for nitrates, moderate pyuria, and/or bacteriuria were accurate predictors of a UTI,²⁶ effectively ruling in the diagnosis of UTI. However, no single test or combination of testing results can effectively rule out UTI in women presenting to the ED with symptoms of cystitis. Therefore, there will be a subset of women for whom test results are equivocal who should either be treated empirically or receive phone-in treatment based on culture, if follow-up cannot be assured in 2 to 3 days.

URINE AND BLOOD CULTURE

For the patient with typical symptoms of cystitis or an uncomplicated UTI and "positive" findings on urinalysis—pyuria on microscopic examination, bacteria in a Gram-stained specimen, positive leukocyte esterase test result, and/or positive urine nitrite test result—urine culture is not required. The vast majority of patients respond to empiric therapy. Urine culture should be performed for the following patients: those with complicated UTI, pregnant women, adult males, patients with relapse or reinfection, and septic patients. If the patient is symptomatic, a single positive culture result is significant.

Results of blood cultures in patients admitted for clinical pyelonephritis are positive in 25% to 29% of cases; organisms in blood culture match those in urine culture in 97% of cases, and blood culture results usually do not alter management. The primary indication for blood cultures in patients with suspected UTI is clinical sepsis.

Renal imaging studies are not indicated in otherwise healthy patients with acute pyelonephritis who can be managed as outpatients. Male, elderly, diabetic, or severely ill patients with acute pyelonephritis should be considered for imaging, particularly if there is a renal stone or a poor initial response to antibiotic therapy. The kidneys can be imaged with bedside US to evaluate for obstruction and focal parenchymal abnormalities. Plain film radiography and US have poor sensitivity for detection of intrarenal gas formation in emphysematous pyelonephritis. If kidney or ureteral stones or emphysematous pyelonephritis are suspected, CT is the best imaging modality.⁹

Table 91-4 lists the differential diagnoses for dysuria.

ACUTE CYSTITIS AND UNCOMPLICATED URINARY TRACT INFECTION

Selection of antibiotics depends on the organism suspected of causing the infection, the patient's ability to adhere to the treatment regimen, local resistance patterns, potential drug toxicity, and cost. The Infectious Disease Society of America and the European Society for Microbiology and Infectious Disease published updated recommendations on antibiotics for uncomplicated UTI in 2010 (Table 91-5).¹² Other guidelines have been incorporated.¹⁰

Table 91-5 contains treatment recommendations for three separate groups of patients with UTI: (1) uncomplicated lower tract disease, (2) complicated UTI or pyelonephritis, and (3) women with UTI symptoms in whom coexistent urethritis cannot be excluded.^10,12

Three-day regimens are recommended for uncomplicated infections in nonpregnant women.¹² A total of 3 to 6 days of therapy is sufficient for treating uncomplicated UTIs in elderly women; however, patient selection guidelines must be strictly adhered to because most elderly women have comorbidities that exclude them from the classification of "uncomplicated UTI."³¹ Trimethoprim-sulfamethoxazole continues to be recommended because it is inexpensive and has limited side effects. Rates of resistance to trimethoprim-sulfamethoxazole are reported to be over the 20% threshold for treatment exclusion in the western and southern United States;³² however, hospital culture data primarily reflect complicated UTI, and trimethoprim-sulfamethoxazole treatment may be successful for uncomplicated UTI.³³ Fosfomycin has less efficacy than short courses of other regimens. Within regions, local resistance patterns vary widely and change rapidly. Currently, recommendations are to avoid trimethoprim-sulfamethoxazole as the first-line empiric agent of choice when local resistance rate exceeds 20%, unless treating based on the results of urine culture with sensitivity testing.

Nitrofurantoin is indicated for treatment of UTI in pregnancy, although it is not effective against Staphylococcus saprophyticus. A 5-day course of extended-release nitrofurantoin is as effective as 3 days of trimethoprim-sulfamethoxazole therapy.³⁴ A single 3-gram dose of fosfomycin is a first-line choice for uncomplicated UTI¹² because the resistance rate is only 2%.³⁵ Both nitrofurantoin and fosfomycin are recommended oral agents in the event of extended-spectrum β-lactamase–producing E. coli infection, because resistance is reported to be only 6% and 3%, respectively.³⁶

Because of bacterial resistance to traditional antibiotics used for UTI, use local sensitivities to guide the substitution of alternative agents such as cephalosporins. Third-generation cephalosporins are highly effective against enterobacteria, whereas first-generation cephalosporins are more effective against staphylococci. Amoxicillin-clavulanate is less effective than fluoroquinolones or oral cephalosporins for UTI due to enterobacteria. It also often leads to selection of Klebsiella. Aminopenicillins are therefore not recommended as first-line therapy in uncomplicated UTI.

If the patient has UTI symptoms and there is also suspicion of Chlamydia or Neisseria gonorrhoeae infection (cervicitis and/or salpingitis), antibiotic treatment is more complex. The patient should be tested³⁷ and empirically treated³⁸ for Chlamydia and N. gonorrhoeae (see Table 91-5; also see chapter 149. Fluoroquinolones were formerly recommended in this setting as a treatment for both cystitis and urethritis, but the Centers for Disease Control and Prevention no longer recommend them due to N. gonorrhoeae resistance. If coexistent cystitis is suspected in a patient with clinical urethritis, add a recommended treatment for cystitis (Table 91-5) to the treatment for urethritis; alternatively, culture the urine and treat for cystitis pending results.

ACUTE PYELONEPHRITIS AND COMPLICATED URINARY TRACT INFECTION

Recommendations for antibiotic therapy and cultures for patients whose condition is stable enough for outpatient treatment are listed in Table 91-5. Antibiotics for inpatient management are listed in Table 91-6.^10,12, For patients whose vital signs are unstable, see chapter 150, "Toxic Shock Syndromes." After clinical improvement has been achieved with parenteral antibiotics, treatment should be changed to oral agents as listed in Table 91-5. Patients may require fluid resuscitation with crystalloids to replace fluid losses due to vomiting or sweating. Although treatment courses as short as 5 days have been studied in patients with pyelonephritis and catheter-associated infections,^9,10 guidelines recommend a total of 7 to 14 days of therapy for the majority, regardless of whether or not parenteral therapy is used.¹⁰ Men with UTI without immunocompromise may have improved outcomes with therapy for 7 days, rather than 14 days.^39,40 For patients with sepsis syndrome, a total of 21 days of treatment may be required to eradicate bacteriuria.¹⁰

RECURRENT INFECTION

Women presenting to the ED with an acute UTI and a history of greater than two UTIs in 6 months or greater than three UTIs in 12 months should be cultured, treated empirically, and referred to a primary care physician in 1 to 2 weeks for repeat culture and possible prophylaxis.^41,42,43 The patient can be treated with recommended treatments for uncomplicated cystitis from Table 91-5 including 3-day regimins,⁴¹ unless the recurrence is a relapse (see "Pathophysiology and Definitions" discussed earlier). Treat relapse with an alternative agent, such as one of those recommended for complicated UTI (Table 91-5).⁴¹ Prophylaxis may take the form of continuous, postcoital, or intermittent self-treatment during symptomatic episodes.^41,42,43 Woman with recurrent UTI using spermicide with contraception should be encouraged to inquire about an alternative method of contraception.^41,42,43

The decision to admit a patient with UTI is based on age, host factors, and response to initial ED interventions. Admit patients who are unable to retain fluids and medication or those with systemic signs of UTI and a stone (see chapter 94, "Urologic Stone Disease"), and choose antibiotics as listed in Table 91-6. Eighty-four percent of patients are discharged.⁴⁴ Healthy females tolerating fluids and medication with uncomplicated pyelonephritis are candidates for outpatient management.⁴⁵ Adjunctive therapies at discharge include increased fluids and frequent voiding to diminish tissue contact with bacteria. An oral bladder analgesic, such as phenazopyridine (200 milligrams PO three times daily), reduces dysuria. Cranberry juice appears to be mildly effective in reducing the incidence of recurrent infection. There is no conclusive evidence that postcoital voiding prevents cystitis.⁴³ Ask patients to return to the ED if they experience increasing pain, fever, or vomiting. Consider systemic analgesics and antiemetics for patients with pyelonephritis.

Overall, approximately 1% to 3% of patients with acute pyelonephritis die from the infection, with younger patients experiencing the fewest complications. Factors associated with an unfavorable prognosis are advanced age and general debility, renal calculi or obstruction, a history of recent hospitalization or instrumentation, diabetes mellitus, evidence of chronic nephropathy, sickle cell anemia, underlying carcinoma, and immunocompromised state (e.g., chemotherapy, human immunodeficiency virus infection/acquired immunodeficiency syndrome [HIV/AIDS]).

Dangerous complications of acute pyelonephritis include acute papillary necrosis with possible ureter obstruction, septic shock, perinephric abscesses, and emphysematous pyelonephritis.

PREGNANCY

See chapter 99 for a detailed discussion.

PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS INFECTION/ACQUIRED IMMUNODEFICIENCY SYNDROME

In HIV/AIDS patients, resistance to TMP-SMX is increased due largely to its use in Pneumocystis jiroveci prophylaxis. Fluoroquinolones should be the initial antibiotic used for UTI in these patients unless urine culture and sensitivity test results are available to guide therapy. Most UTIs in HIV/AIDS patients are caused by typical pathogens or common sexually transmitted disease organisms. Mycobacterium tuberculosis is an infrequent cause of UTI in the HIV/AIDS population. Close outpatient follow-up (recheck in 1 week) and possible infectious disease consultation are warranted when treating UTI in this population (see chapter 154, "Human Immunodeficiency Virus Infection").

PRACTICE GUIDELINES

The European Association of Urology updates its "Guidelines on Urogenital Infections" yearly.¹⁰ The Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases updated its "International Clinical Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women" in 2010.¹² "Complicated Urinary Tract Infection in Adults" guidelines were published by the Canadian Association of Medical Microbiology and Infectious Diseases in 2005.¹¹

INTRODUCTION AND EPIDEMIOLOGY

Gross hematuria is visible to the eye, whereas microscopic hematuria is a laboratory diagnosis. Other pigments, particularly myoglobin, may discolor the urine and simulate gross hematuria. UTI is the most common cause of hematuria associated with urgency, dysuria, and nocturia^26,27; however, these symptoms are also common in the much smaller group of patients who ultimately are diagnosed with cancer of the urinary tract.^46,47 Painless hematuria is more often due to neoplastic, hyperplastic, and vascular causes.

It takes approximately 1 mL of whole blood per liter of urine to result in visible hematuria. Gross hematuria may also result in false proteinuria. The incidence of gross hematuria in the general population and in patients presenting to the ED is unknown. However, gross hematuria is more common in premenopausal women due to UTIs and contamination with menstrual blood.⁴⁸ The incidence of bladder cancer associated with gross hematuria rises with increasing age.

The American Urological Association recently redefined microscopic hematuria as ≥3 red blood cells (RBCs)/HPF (400×) on a properly collected and centrifuged urinary specimen in the absence of an obvious benign cause,⁴⁸ removing the prior American Urological Association requirement for a positive repeat specimen (one of the next two) as part of the definition. Hematuria from malignant causes is frequently intermittent.⁴⁸ Normal urine contains a small number of RBCs, usually too few to be detected by routine chemical dipstick testing or microscopic urinalysis. Population-based studies have found at least one episode of transient microscopic hematuria in 4% to 13% of individuals.

Any process that results in infection, inflammation, or injury to the kidneys, ureters, bladder, prostate, male genitalia, or urethra may result in hematuria (Tables 91-7 and 91-8).⁴⁹

In men >50 years old, tumors of the prostate or elsewhere in the ejaculatory system and benign prostatic hypertrophy are considerations when hematuria is present. In patients <40 years, common causes are infections and inflammatory conditions, including prostatitis, urethritis, sexually transmitted diseases, epididymo-orchitis, calculi with inflammation, and tuberculosis. Testicular tumors may occur in men younger than 50 years old.

False hematuria occurs when the urine appears bloody but dipstick test results are negative for blood and there are no RBCs on microscopic evaluation, or blood has been added to a previously blood-free specimen by the patient (Table 91-9). Free hemoglobin, myoglobin, or porphyrins in the urine result in a positive urine test strip reaction for blood.

A careful history, including information regarding sexual activity, recent urologic procedures, medications used, and HIV and tuberculosis risk factors, should be obtained. The patient's general health and condition, vital signs, abdomen, external genitalia, and prostate in males should be evaluated.

Initial hematuria is the appearance of blood at the beginning of micturition, with subsequent clearing, and suggests urethral disease including cancer. Gross hematuria more often indicates a lower tract cause.²⁶ In younger patients, microscopic hematuria is most often caused by nephrolithiasis or UTI.²⁶ In older patients, infections and nephrolithiasis remain common causes of hematuria; however, hematuria in patients >50 years old warrants follow-up because renal, bladder, and prostate cancer increase in frequency and may coexist with UTI or kidney stones.^46,48 Risk factors for uroepithelial cancer are age >50 years, male sex, smoking, family history of bladder cancer, occupational exposures in the chemical, rubber, or leather industries (e.g., exposure to dyes, benzenes, or aromatic amines), and excessive analgesic use.⁴⁶ Hematuria in a patient taking oral anticoagulants should not be attributed to the anticoagulant alone, because the incidence of underlying disease is up to 80% in patients referred to urology for evaluation.⁴⁶ Expanding abdominal aortic aneurysms may erode into the urogenital tract or cause inflammation or obstruction from direct pressure.

Malignant hypertension, embolic renal infarction, and renal vein thrombosis are other serious diagnoses that can cause hematuria. In pregnancy, hematuria can be associated with UTI, nephrolithiasis, or pre-eclampsia. Recent instrumentation of the urinary tract may produce hematuria.

The reported incidence of hematuria in HIV-infected patients is 18% to 50%. Causes include UTI, chlamydial and gonococcal urethritis, glomerulonephritis, neurogenic bladder, thrombocytopenia, subclinical uroepithelial Kaposi's sarcoma, and urethral trauma. However, in up to 80% of patients, no specific cause is found.

The physical examination should note the vital signs and the patient's appearance. Hypertension and edema imply nephrotic syndrome. A new heart murmur (endocarditis) or atrial fibrillation increases the likelihood of embolic disease and renal infarction. A full genital-urinary examination is essential for both males and females. Systemic signs need to be correlated to potential diseases that cause hematuria (Table 91-8).

Potential causes of hematuria are often suggested by considering the patient's age, sex, demographic characteristics, habits, potential risk factors, history of recent GU instrumentation, and comorbidities.⁴⁸

LABORATORY TESTING

A clean-catch midstream urine collection is appropriate for most patients. Catheter-collected specimens are recommended for women with a vaginal discharge or menstrual or vaginal bleeding; however, urethral catheterization induces hematuria in 15% of patients. Brown or smoke-colored urine, along with dysmorphic RBCs, cellular casts, and proteinuria, suggests a glomerular source.⁴⁸ Red, clotted blood in the urine indicates a source below the kidneys.

A urine dipstick test for blood can detect as little as 150 micrograms/L of free hemoglobin, corresponding to 5 to 20 intact RBCs/mL on microscopic analysis. False-negative results may be obtained with urine dipstick tests for blood if the urine has a high concentration of ascorbic acid (>5 milligrams/dL) or a high specific gravity. False-positive results occur in the presence of free hemoglobin, myoglobin, or porphyrins.

For patients with a clinical picture that does not provide a clear cause of hematuria on dipstick analysis (or indication for an urgent evaluation), urinalysis with microscopy should be performed to confirm hematuria before further work-up.⁴⁸ Hemorrhagic cystitis with invasive infection of the bladder wall by bacteria resulting in shedding and bleeding is a common cause of hematuria and resolves with appropriate antibiotic treatment.

For patients taking anticoagulants, obtain appropriate coagulation studies in the ED, with imaging at follow-up for older patients to exclude malignancy.

The finding of normal RBCs on microscopic examination of the urine together with bacteriuria and leukocytes in a young healthy patient supports UTI as the probable cause of hematuria. Additional laboratory studies may be needed depending on the results of the history, physical examination, and presumptive differential diagnosis. The presence of normal RBCs without evidence of infection should prompt further urologic evaluation to determine the site of bleeding; however, in stable patients without an urgent cause suggested by history and physical examination, an outpatient evaluation is appropriate.

IMAGING

Initial upper and lower urinary tract imaging for hematuria is now typically done with noncontrast helical CT or renal US.^48,50 Helical CT clearly delineates most renal tumors, obstructions, or stones and their precise location.^48,50

Renal US is useful when screening for obstruction, hydronephrosis, or abdominal aortic aneurysm. It is the study of choice in pregnant patients with suspected nephrolithiasis. However, renal US rarely identifies or locates stones in the ureters that are not large enough to give findings of obstruction. Renal US also does not provide any assessment of renal function—normal enhancement and excretion of contrast by both kidneys. Helical CT with contrast provides this important information.

Gross hematuria in patients with blunt or penetrating trauma to the abdomen, flank, or back warrants an aggressive approach to identify the source of bleeding and to guide management (see chapter 265, "Genitourinary Trauma").⁴⁸

Treatment of hematuria is directed at the cause (Tables 91-7 and 91-8). Outpatient management and referral for follow-up are appropriate for patients in hemodynamically stable condition without an apparent life-threatening cause of the hematuria. The urgency for follow-up depends on the presence of gross hematuria or risk factors for significant disease (Table 91-10).^48,50 Patients with gross hematuria or listed significant risk factors should ideally be reevaluated at follow-up within 2 weeks.

The American Urological Association guideline recommends referral to urology to assess for urinary tract malignancy in all patients with microscopic hematuria without an obvious benign cause.⁴⁸, Follow-up within 1 month is acceptable for patients with microscopic hematuria without significant risk factors.

Gross hematuria may lead to intravesical clot formation and bladder outlet obstruction. See chapter 92, "Acute Urinary Retention" for management.

Patients with intractable pain, intolerance of oral fluids and medications, significant comorbid illness, bladder outlet obstruction, evidence of hemodynamic instability, or possible life-threatening causes of hematuria should be admitted, and the appropriate specialist should be consulted.

PRACTICE GUIDELINES

Practice guidelines include those from the American Urological Association.⁴⁸