A. Introduction. Urinary tract infections (UTIs) are extremely common and include cystitis, pyelonephritis, and urosepsis.
a. Etiology. Escherichia coli accounts for approximately 80% of all infections. Staphylococcus saprophyticus, group B Streptococcus, Klebsiella species, Proteus mirabilis, Enterococcus species, and other bacteria account for the rest.
i. Women are more susceptible than men to UTIs because the female urethra is shorter and straighter—factors that facilitate bacterial access to the bladder. In addition:
1. Sexual intercourse and the use of diaphragms and spermicide are predisposing factors for UTI in women.
2. In postmenopausal women, estrogen deficiency may predispose patients to acute cystitis (from increased colonization with E. coli).
ii. In men, UTI is often associated with urinary obstruction (e.g., bladder outlet obstruction due to prostate enlargement).
iii. In both men and women, UTI may be caused by obstruction due to nephrolithiasis or use of indwelling catheters.
B. Clinical Manifestations of Urinary Tract Infections
a. Dysuria (i.e., pain or burning with urination) is usually present and is commonly associated with other irritative symptoms (i.e., urinary frequency, urgency, and nocturia). Although dysuria often indicates acute cystitis, it is important to remember that other disorders may also present with dysuria.
MNEMONIC: A “FUND” of irritative symptoms may indicate the presence of a UTI:
b. Suprapubic or costovertebral angle pain or tenderness is usually indicative of cystitis or pyelonephritis, respectively.
c. Fever usually indicates a systemic response, possibly due to pyelonephritis. Hypotension and altered mental status may indicate sepsis in the setting of urinary tract infection.
C. Differential Diagnosis of Dysuria. Dysuria does not always signal acute cystitis. It is especially important to consider the alternative causes of dysuria in men because acute cystitis is less common in men than in women. Non-UTI causes of dysuria (by gender) include the following:
i. Infectious causes
1. Urethritis (e.g., from Neisseria gonorrhea, Chlamydia trachomatis, or herpes simplex virus) causes dysuria. Compared with the dysuria from acute cystitis, the dysuria of urethritis usually evolves gradually, is less severe, and is less often accompanied by urinary frequency and urgency. A history of vaginal discharge or a new sexual partner also raises suspicion for urethritis.
2. Vaginitis (e.g., from Candida or Trichomonas) usually presents with a malodorous vaginal discharge. The patient may also complain of dyspareunia.
ii. Noninfectious causes
1. Interstitial cystitis may present with dysuria, urinary leukocytes, and a negative urine culture. Interstitial cystitis can be caused by infectious and noninfectious causes infiltrating the bladder wall.
2. Chemotherapy and pelvic irradiation may cause symptoms that mimic UTI.
3. Nephrolithiasis often presents with dysuria.
i. Bladder pathology may result in dysuria in both men and women, but the relative paucity of UTIs in men increases the likelihood that some other diagnosis is responsible. Both bladder stones and tumors should be considered in men with dysuria.
ii. Prostate syndromes. With the exception of acute bacterial prostatitis (which usually results in dysuria that is accompanied by significant systemic toxicity), prostate syndromes may be easily confused with cystitis. Laboratory testing is usually needed to differentiate among these disorders (see section E in this chapter).
iii. Urethritis from gonorrhea or chlamydia is often associated with purulent penile discharge.
iv. Nephrolithiasis often presents with dysuria and hematuria.
D. Laboratory Studies. Not all the following tests need to be obtained in every patient. The indications for tests are discussed in section E.
a. Urine dipstick testing allows for the determination of urinary pH, leukocyte esterase, nitrite, blood, and protein levels.
i. Urinary pH. An alkaline urine may indicate a urea-splitting organism (e.g., Proteus).
ii. Leukocyte esterase usually indicates the presence of inflammatory cells (i.e., white blood cells [WBCs]) and therefore infection. The sensitivity may exceed 75%. False-positive results may occur with urinary contamination.
iii. Nitrite is detected when certain species of the Enterobacteriaceae family are present. The sensitivity is relatively low, and false-positive results are noted with bacterial contamination. The presence of nitrite without leukocyte esterase does not necessarily suggest UTI.
iv. Blood in the urine may indicate myoglobin, hemoglobin, or intact red blood cells (RBCs). Cystitis can cause hematuria, but other causes of bladder pathology should also be considered (e.g., a malignancy anywhere along the urinary tract).
v. Protein in the urine may indicate a glomerulopathy, although low levels of proteinuria occur in bladder irritation or hematuria. Large numbers of WBCs may lead to a false-positive protein determination.
b. Urine microscopic analysis. The presence of more than 5 leukocytes per high-power field denotes pyuria and is indicative of some urinary tract abnormality. Gram staining may also be performed but is not a sensitive test for UTI. Sterile pyuria (i.e., pyuria with a negative urine culture) may occur with contained bacterial infections (renal abscesses), systemic bacterial infections (endocarditis), nonbacterial infections (miliary tuberculosis), inflammatory processes (interstitial nephritis), and partially treated UTI.
c. Urine culture is the gold standard for diagnosing UTI. Previously, a colony count of 105 was considered the cutoff point for diagnosing a UTI, but more than 50% of symptomatic women have a lower colony count. In fact, the presence of as few as 100 colonies may signal infection in a woman who has symptoms.
d. Prostatic secretion analysis. Prostatic secretions may be elicited through prostate massage. In older adult men with possible chronic prostatitis, a urinalysis with culture is often sent before and after prostate massage.
e. Urine pregnancy test. Because pregnant patients are often treated with different antibiotics and with a longer course of therapy, a urine pregnancy test should be obtained in patients for whom pregnancy is a possibility.
f. Renal imaging (ultrasound or computed tomography [CT] scan). In patients who are systemically ill, and especially in those with a history of kidney stones or a presentation compatible with urolithiasis, an ultrasound may be obtained to rule out “pus under pressure” (i.e., an infection behind an obstruction that mimics an abscess).
E. Approach to the Patient
a. Uncomplicated cystitis
i. Women. Empiric treatment is an appropriate approach in healthy, nonpregnant women who present with the classic symptoms of acute UTI without any evidence of pyelonephritis (i.e., no systemic symptoms such as fever, costovertebral angle pain, or nausea) or another cause of dysuria (urethritis, vaginitis). Another option is to obtain a urinary dipstick, which is usually the only test that is required. If the urinary dipstick is negative or the patient has pelvic pain or abnormal vaginal discharge, a pelvic examination and a urine culture are indicated.
ii. Men. A urine dipstick and culture are generally performed before therapy.
b. Uncomplicated pyelonephritis. Patients usually present with irritative symptoms associated with fever, costovertebral angle pain or tenderness, or both. The urinary dipstick is usually positive, and a urine culture is usually sent for definitive diagnosis and to ascertain the antimicrobial sensitivities of the causative organism.
c. Recurrent cystitis (e.g., three or more episodes per year) is much more common in women than men. Before diagnosing recurrent cystitis, rule out relapse.
i. If the relapses occur early after the completion of therapy, the same species and strain of organism is isolated, then additional urologic evaluation is usually necessary.
ii. If the recurrences occur later, a different organism is isolated, then additional evaluation (e.g., for structural abnormalities of the urinary tract) is often unnecessary.
d. Complicated UTIs may occur in men or women and are often suspected in patients whose conditions relapse or do not improve with initial therapy. A complicated infection results when a patient has an anatomic or functional abnormality of the urinary tract or a resistant infection. Catheter-associated UTI (see Chapter 4) is considered to be complicated. A urine culture is always recommended in these cases.
e. Asymptomatic bacteriuria. In most patients, screening for asymptomatic bacteriuria is unnecessary. Exceptions include:
i. Pregnant women are screened and treated if the bacteria count is 10,000 CFU/mL or more (to decrease the risk of pyelonephritis).
ii. Patients undergoing renal or urologic procedures also benefit from screening.
f. Prostate syndromes. The presence of obstructive symptoms (i.e., hesitancy, difficulty starting and stopping the stream, decreased urinary flow) may favor a diagnosis of chronic prostatitis or prostatodynia. Of note, prostate tenderness on examination is not a sensitive marker for these disorders. If a prostate syndrome is suspected, a urine sample is obtained for urinalysis and culture, and then a second sample is obtained following prostate massage.
i. Chronic bacterial prostatitis. An increase in leukocytes usually occurs with massage; culture of prostatic secretions is positive.
ii. Chronic inflammatory nonbacterial prostatitis usually demonstrates an increase in leukocytes after massage, but the culture is negative.
iii. Chronic noninflammatory, nonbacterial prostatitis (prostatodynia) is a diagnosis of exclusion that is made when the patient has typical symptoms but no increase in leukocytes with massage and a negative culture.
a. Uncomplicated cystitis. Empiric therapy is generally appropriate when the urine dipstick test is positive. It may also be appropriate for patients with no alternative diagnosis and a high clinical suspicion for UTI.
i. Trimethoprim (TMP)/sulfamethoxazole (SMX) (e.g., TMP 160 mg/SMX 800 mg) can be administered orally twice daily for 3 days. A longer course of therapy (e.g., 7 days) may be appropriate in higher risk patients (e.g., patients with diabetes, older adult patients). Men should be treated for 7 days.
ii. Nitrofurantoin and fosfomycin are recommended as other first-line agents. Nitrofurantoin must be given for at least 5 days. Fosfomycin can be given as a one-time single dose.
iii. Fluoroquinolones are second-line agents that can be substituted if the patient has a sulfa allergy or if resistant strains have emerged in the local area. Always think twice before using fluoroquinolones because important side effects such as tendon rupture and Clostridium difficile may occur with these agents.
iv. β-Lactams such as amoxicillin are second-line agents that are generally less efficacious than the first-line agents listed previously.
v. Amoxicillin or nitrofurantoin can be given in pregnancy.
b. Resistance. There is growing worldwide resistance of E. coli to typical antibiotic choices.
i. Amoxicillin and TMP/SMX resistance is estimated to be >20%.
ii. Oral cephalosporins, amoxicillin/clavulanate, and fluoroquinolones resistance is generally <10% but is increasing.
c. Uncomplicated pyelonephritis
i. Outpatient treatment is appropriate for many patients. TMP/SMX (TMP 160 mg/SMX 800 mg orally twice daily) may be prescribed for 14–21 days unless resistant strains of bacteria have emerged in the area (in which case a fluoroquinolone would be an appropriate agent).
ii. Inpatient treatment may be necessary for diabetic patients, older adult patients, and patients who appear severely ill or are unable to maintain hydration secondary to nausea and vomiting. Inpatient treatment is also recommended for pregnant patients. A third-generation cephalosporin, a fluoroquinolone, or the combination of ampicillin and gentamicin is often used.
d. Recurrent cystitis is often an indication for prophylaxis.
i. General recommendations. Postmenopausal women may benefit from topical estrogen to help prevent E. coli colonization. Women who use diaphragms or spermicide should consider alternative methods of birth control. These measures may obviate the need for prophylaxis.
1. Postcoital prophylaxis is often used in patients who relate their UTIs to sexual intercourse. TMP/SMX, nitrofurantoin, or cephalexin may be taken after intercourse, and patients should be advised to urinate soon after intercourse.
2. Daily prophylaxis with TMP/SMX, nitrofurantoin, or cephalexin may be used in patients with recurrent UTIs unrelated to sexual intercourse. Less frequent strategies such as thrice-weekly TMP/SMX or fosfomycin every 10 days is also effective.
3. Self-diagnosis/early therapy may be preferred in patients who have infrequent recurrences (e.g., two episodes per year). Patients initiate their own 3-day treatment with the onset of symptoms.
e. Complicated UTIs. If a resistant organism is the cause, therapy is generally aimed at the organism and often given for an extended period (e.g., 10–14 days or longer). A fluoroquinolone may be used in outpatients, while broad-spectrum intravenous antibiotics may be required for initial inpatient therapy. If the infection is related to the use of a urinary catheter (see Chapter 4), urine culture and appropriate antimicrobial treatment for 7–14 days is usually required.
If a patient develops a catheter-related infection and still needs the indwelling urinary catheter, the catheter should be replaced before initiating antimicrobial treatment (because biofilm development along the surface of the catheter harbors microorganisms and may “protect” them from the antimicrobial agent).
f. Prostate syndromes
i. Chronic bacterial prostatitis. Prolonged treatment for 4–6 weeks is required, preferably with a fluoroquinolone.
ii. Chronic nonbacterial prostatitis (inflammatory and noninflammatory). Often treated as chronic bacterial prostatitis with a prolonged course of antibiotics, although the efficacy of this practice is questionable. This should not be repeated unless positive cultures are later obtained.
iii. α-blocking agents may help relieve bladder neck and urethral spasms associated with bacterial and nonbacterial causes of prostatitis.
Suggested Further Readings
Chenoweth CE, Gould CV, Saint S. Diagnosis, management, and prevention of catheter-associated urinary tract infections. Infect Dis Clin North Am 2014;28:105–19.Find this resource:
Gupta K, Hooton TM, Naber KG, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: a 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52:e103–e20.Find this resource:
Lipsky BA, Byren I, Hoey CT. Treatment of bacterial prostatitis. Clin Infect Dis 2010;50:1641–52.Find this resource:
Nicolle LE. Uncomplicated urinary tract infection in adults including uncomplicated pyelonephritis. Urol Clin North Am 2008;35:1–12.Find this resource:
Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016;62:e1–e50.Find this resource: