Current Diagnosis & Treatment in Infectious Diseases

Section II - Clinical Syndromes

16. Urinary Tract Infections

Walter R. Wilson MD

Nancy K. Henry PhD, MD

COMMUNITY-ACQUIRED URINARY TRACT INFECTIONS

Essentials of Diagnosis

Acute Cystitis-Urethritis

  • Women and girls older than 2 years.
  • Acute onset dysuria, increased frequency urination.
  • Pyuria ≥ 5–10 erythrocytes/high-power field of centrifuged urine or positive leukocyte esterase test.
  • Positive urine culture (1000–100,000 colony forming units/mL) for Escherichia coli, other Enterobacteriaceae, enterococci, or Staphylococcus saprophyticus.

Acute Pyelonephritis

  • Fever, chills, flank pain.
  • Pyuria.
  • Positive urine Gram stain for gram-negative bacilli.
  • Positive urine culture (≥ 100,000 colony forming units) or blood culture with gram-negative bacilli.

Acute Prostatitis (subjects older than age 35)

  • Fever, chills, dysuria, increased frequency of urination, low back or pelvic pain.
  • Pyuria.
  • Positive urine culture for gram-negative bacilli or enterococci.

Chronic Prostatitis

  • Middle-aged to elderly men.
  • Chronic intermittent dysuria, increased frequency of urination, pelvic pain.
  • Enlarged prostate.
  • Positive culture of prostatic secretions or voided urine after massage for gram-negative bacilli or enterococci. The number of colony forming units of bacteria should be 10-fold greater than the number in urine obtained before prostatic massage.

General Considerations

Infections involving the urinary tract are among the most common infectious diseases. Bacteriuria is defined as bacteria present in the urine. Bacteriuria may be asymptomatic or may be present in association with acute or chronic infection of the kidney, bladder, prostate, or urethra. Acute cystitis-urethritis is a syndrome consisting of dysuria, urgency, and increased frequency of urination with or without upper tract infection. Acute pyelonephritis is an infection of the kidneys and is described as a syndrome of fever and flank pain with or without dysuria. The term acute prostatitis describes a syndrome of fever, perineal and low-back pain, dysuria, urgency, and increased frequency of urination. Chronic urinary tract infection (UTI) refers to persistence or frequent reinfection of the kidney, bladder, or prostate.

  1. Epidemiology.
  2. Children.During infancy, the frequency of bacteriuria is 1–2% and is more common in boys during the first 3 months; thereafter, it is more common in girls. Lack of circumcision increases the risk of UTI in infant males. Among preschool children, bacteriuria is more common in females than in males, and, when present in males, bacteriuria is usually associated with congenital abnormalities. The prevalence of bacteriuria among school girls is 1–2%, and ≥ 5% have bacteriuria before finishing high school. Of these girls, ~ 3% develop symptomatic UTI. School girls with bacteriuria are at greater risk of developing bacteriuria in adulthood. Bacteriuria is rare among school boys, and, when present, it is associated with structural abnormalities.
  3. Adults.Prevalence of bacteriuria in nonpregnant females is 1–3%. At least 10–25% of females develop symptomatic UTI during their lifetimes. The risk of subsequent UTIs is greater than the risk of the initial UTI. The prevalence of bacteriuria among adult men is low (< 0.1%) and is associated with anatomic abnormalities, such as obstruction.
  4. Pregnancy.Pregnant women are at increased risk of bacteriuria, and the prevalence ranges from 4–7%. Beginning as early as the seventh week of gestation, dilatation of the uterus and renal pelvis occurs, and the bladder tone decreases, which may result in urinary stasis in the bladder. The majority of pregnant women with bacteriuria have bacteriuria detected at the first prenatal visit. Of pregnant women with bacteriuria, ~ 25% develop their infection during pregnancy.

 

Bacteriuria during pregnancy increases the risk of pyelonephritis during the latter stages of pregnancy. If untreated, ~ 20–40% of patients with bacteriuria early in pregnancy develop acute pyelonephritis later in pregnancy. Of pregnant women without bacteriuria early in gestation, < 1% develop acute pyelonephritis, which emphasizes the importance of early detection and treatment. Acute pyelonephritis is associated with premature delivery in 20–50% of patients. The eradication of bacteriuria probably reduces the frequency of prematurity and low birth weight. The association of bacteriuria and hypertension in pregnancy is not clear.

  1. Elderly.Among individuals older than 65 years, ≥ 10% of men and 20% of women have bacteriuria. Risk factors include prostatic hypertrophy in males, bladder prolapse in females, soiling of the peritoneum, neurogenic bladder, and the use of a chronic indwelling urinary catheter.
  2. Microbiology.E coliis the most common cause of acute uncomplicated community-acquired UTI, accounting for ~ 95% of cases. In recurrent infections, especially in association with structural abnormalities, the relative frequency increases for infection caused by other microorganisms, such as Proteus species, Klebsiella species, Enterobacter species, and enterococci. Nosocomial acquisition, especially in association with urinary catheterization, is often caused by E coli, Pseudomonas species, or other gram-negative nosocomial microorganisms (see section on “Nosocomially Acquired Infection” later in this chapter). Urea-splitting microorganisms, such as Proteus species, are associated with calculus formation. S saprophyticus accounts for 5–15% of acute cystitis in young sexually active females. Type 2 adenovirus may cause acute hemorrhagic cystitis in children and is more common in young boys than in girls.
  3. Pathogenesis.
  4. Routes of infection.Bacteria may cause UTIs by three possible routes: ascending, hematogenous, or lymphatic. Of these, the ascending route, especially in women, is probably the most common. Uropathogenic microorganisms colonize the vaginal introitus and periurethral area where they may ascend through the urethra, enter the bladder, multiply, and ascend the ureters to the renal pelvis and parenchyma. Urethral massage, sexual intercourse, or other factors enhance entry of microorganisms into the female urethra. In the male urethra, the mechanism of ascending infection is less understood than in females. Hematogenous infection of the kidney occurs uncommonly in gram-negative bacteremia, although gram-negative bacteremia originating from the urinary tract is one of the most common sources of bacteremia. S aureusbacteremia may cause intrarenal or perinephric abscess. Lymphatic spread of infection to the urinary tract is thought to be uncommon.
  5. Microbial factors.Although virtually any microorganism is capable of causing UTI, E coliis responsible for the majority of infections (Box 16-1). Uropathogenic strains of E coli are selected from the fecal flora by the presence of virulence factors that enhance colonization of vaginal and periurethral cells, attachment to uroepithelium, and invasion of tissue. These factors include adhesions, resistance to serum bactericidal activity and phagocytosis, presence of a high amount of K antigen, and hemolysin production. Of these, adhesion is the most important property of uropathogenic E coli.

Fimbriae are the major type of surface adhesions of uropathogenic E coli. A number of specific, morphologic and functional E coli fimbriae have been identified. The two most important of these are P fimbriae and type 1 fimbriae. E coli expressing P fimbriae attach to globoseries, glycolipid receptors in the kidney, and are the strains most associated with acute pyelonephritis. These receptors are distributed throughout the urinary tract but are most prevalent in the kidney. The attachment of these strains is not inhibited by mannose, and the strains are referred to as mannose resistant. Type 1-fimbriaed E coli bind to mannose-containing receptors in the urinary tract and are more likely to cause cystitis than pyelonephritis. Attachment of these strains is inhibited in the presence of mannose, and these strains are referred to as mannose susceptible. Type 1 fimbriae increase the susceptibility of E coli to phagocytosis, but uropathogenic E coli fail to express type I fimbriae in renal parenchyma. Polymorphonuclear leukocytes lack a receptor for P fimbriae, which inhibits the phagocytosis of these strains. Nonfimbriated uropathogenic E coli bacteria express a variety of adhesions that bind to uroepithelium.

Proteus mirabilis and Klebsiella species also express fimbriae, which are responsible for attachment. S saprophyticus adheres more readily to uroepithelial cells than does Staphylococcus epidermidis or S aureus. The production of urease by Proteus species and other microorganisms increases the potential of these microorganisms to cause pyelonephritis. Bacterial K-antigen inhibits phagocytosis. Most uropathogenic bacterial strains produce hemolysins, which facilitate tissue invasion and enhance renal cell damage.

  1. Host factors.Many host factors increase susceptibility to UTI. The most common of these is obstruction of normal urinary flow, resulting in stasis. This may occur as the result of extrarenal obstruction from congenital abnormalities, malignancies, calculi, vesicoureteral reflux, prostatic hypertrophy, neurogenic bladder, pregnancy, or other conditions.

Vesicoureteral reflux caused by congenital abnormalities or neurogenic bladder is highly associated with UTI. Reflux results in a residual pool of urine in the bladder after voiding which, when infected, predisposes to upper tract infection and renal scarring. Incomplete bladder emptying from any cause, such as prostatic hypertrophy, similarly results in residual urine in the bladder, which increases susceptibility to UTI.

Urinary tract instrumentation is another common cause of UTI. A single catheterization of the bladder results in bacteriuria in 0.1–1% of patients. Virtually all patients with a chronic indwelling urinary catheter develop UTI.

In sexually active women, the use of a diaphragm with spermicidal jelly increases the susceptibility to UTI. Spermicide may cause pH changes that increase colonization of the vagina with uropathogens. Diabetics are more susceptible to infection in general, including UTI. The presence of glucose in the urine enhances bacterial growth.

A variety of factors protect the host from UTI. With the exception of the urethral mucosa, the normal urinary tract is resistant to colonization by bacteria and rapidly clears most microorganisms that gain access to the bladder. High or low urine osmolality, high urea concentration, and low urinary pH inhibit the growth of microorganisms. Tamn-Horsfall protein secreted by cells in the ascending loop of Henle contains mannose, which binds type 1-fimbriated E coli. Mannose-bound strains prevent microorganisms from binding to uroepithelial cells, and the complexes are flushed from the urinary tract during micturition. Prostatic secretions contain zinc, which inhibits growth of bacteria in urine.

BOX 16-1 Microbiology of Community-Acquired Urinary Tract Infection

Dysuria-Pyuria Syndrome in Females

 

Children

Adults

More Frequent

· Escherichia coli

· E coli

· Staphylococcus saprophyticus (young, sexually active patients)

Less Frequent

· Other Enterobacteriaceae

· Enterococci

· Streptococcus agalactiae

· Other Enterobacteriaceae

· Enterococci

Other Community-Acquired Infection

 

Children

Adults

More Frequent

· E coli

· E coli

Less Frequent

· Other Enterobacteriaceae

· Enterococci

· Other Enterobacteriaceae

· Enterococci

Clinical Findings

  1. Signs and symptoms.Many patients with bacteriuria, especially older patients, are asymptomatic. Among neonates and children < 2 years of age, symptoms may be nonspecific and include fever, vomiting, irritability, and failure to thrive. Children older than 2 years usually develop increased frequency of urination and dysuria; with acute pyelonephritis, nausea, vomiting, fever, chills, and flank and abdominal pain may occur.
  2. Acute cystitis-urethritis.Adult women with acute cystitis-urethritis typically have acute onset of dysuria, urgency, and increased frequency of urination. Fever is usually not present in uncomplicated cystitis-urethritis. Physical examination in women with cystitis-urethritis may reveal suprapubic tenderness.
  3. Acute pyelonephritis.Adults with acute pyelonephritis present with fever, chills, and flank or back pain. On physical examination, flank tenderness is common.
  4. Acute prostatitis.Men with acute prostatitis complain of fever, chills, and perineal and low-back pain together with dysuria and increased frequency of urination. The prostate is exquisitely tender in men with acute prostatitis. Physical examinations of the prostate in acute prostatitis should be avoided because of severe pain and the risk of inducing bacteremia.
  5. Chronic prostatitis.Men with chronic prostatitis describe chronic intermittent episodes of dysuria and increased frequency of urination. On physical examination, the prostate is often enlarged, and tenderness may be present but is often absent.
  6. Laboratory findings.
  7. Urinalysis and Gram stain.A urinalysis should be performed in all patients suspected of having a UTI. The large majority of patients with symptomatic UTI have pyuria, described as 5–10 leukocytes/high-power field of centrifuged urinary sediment. A dipstick leukocyte esterase test is a rapid screening test and has a high sensitivity and specificity for detection of pyuria. Leukocyte casts are commonly present in patients with pyelonephritis. Microscopic or gross hematuria may occur in patients with cystitis-urethritis.

 

The presence on Gram stain of ≥ 1 bacterium/high-power field, performed on a midstream clean-catch urine specimen, correlates with ≥ 105bacteria/mL of uncentrifuged urine. Automated screening tests for detection of bacteria are available to rapidly screen large numbers of specimens.

  1. Quantitative urine culture and antimicrobial susceptibility tests.A quantitative urine culture with antimicrobial susceptibility tests is not necessary in most women with urethritis-cystitis. Urine culture and susceptibility studies should be performed in women who relapse after short-course antimicrobial therapy or in those with frequent recurrence of UTI. A quantitative urine culture and antimicrobial susceptibility tests should be performed in all patients that are suspected of having pyelonephritis. Patients with symptomatic UTIs typically have ≥ 105bacteria/mL of midstream clean-catch urine. However, ≥ 40–50% of females with acute cystitis-urethritis have < 105 bacteria/mL of urine, and infection may be present with counts as low as ≥ 1000 bacteria/mL. The presence of < 1000 bacteria/mL of urine suggests a diagnosis other than UTI. Females with acute cystitis-urethritis and sterile pyuria should be suspected of having urethritis caused by Chlamydia trachomatis or Neisseria gonorrhoeae.
  2. Blood cultures.Blood cultures are frequently positive in patients with acute pyelonephritis and should be obtained in all patients in whom this diagnosis is suspected.
  3. Laboratory diagnosis of prostatitis.
  4. Acute prostatitis.Acute prostatitis is most often caused by E colior another member of the family Enterobacteriaceae. Expressed prostatic secretions contain polymorphonuclear leukocytes, and microorganisms are usually present on Gram stain and may be recovered from culture. However, prostatic massage should be avoided in these patients because the prostate is exquisitely tender to palpation, and massage may result in bacteremia. The clinical presentation of acute prostatitis is highly suggestive of the diagnosis, and the microorganism may be recovered from cultures of midstream urine. Antimicrobial susceptibility tests should be performed.
  5. Chronic prostatitis.Of chronic prostatitis cases, ≥ 80% are caused by E coli;the remaining cases are caused by Klebsiella, enterococci, Enterobacter spp., and P mirabilis. Because bacteria in the urethra may contaminate prostatic secretions, the diagnosis requires simultaneous sequential quantitative cultures of four specimens: (1) urethral urine, (2) midstream urine, (3) prostatic secretions expressed by massage, and (4) voided urine after massage. Diagnosis is made by comparing the results of quantitative cultures. The diagnosis is suggested when the number of bacteria in the prostatic massage secretions exceeds those in specimens number 1 and 2 by ≥ 10-fold. If no prostatic secretion fluid is obtained, the postmassage urine quantitative culture should exceed cultures from specimens 1 and 2 by ≥ 10-fold. Antimicrobial susceptibility tests should be performed.
  6. Imaging.Imaging studies should be performed in adult patients with complicated UTIs, such as those with urolithiasis or pyelonephritis, and in patients of any age in whom structural abnormalities are suspected. A plain abdominal roentgenogram may detect urolithiasis, a mass, or an abnormal gas pattern, all of which are suggestive of abscess. Previously, excretory urography or intravenous pyelography (IVP) was the most commonly used imaging technique. However, administration of the contrast material used in IVP may cause an allergic reaction or exacerbate renal insufficiency. Ultrasound imaging and computed tomographic (CT) scans are more sensitive than IVP for detection of renal pathology, and administration of contrast material is not necessary with ultrasonography. Compared with IVP, contrast-enhanced CT scans provide better parenchymal delineation but are less optimal to delineate the collecting system than is IVP. Ultrasonography is useful to detect urinary tract obstruction, and small calculi may be detected by spiral CT scans. Perinephric abscess, renal abscess, and emphysematous pyelonephritis may be diagnosed adequately by ultrasonography or CT scans. The detection of papillary necrosis requires contrast-enhanced urography (IVP) or CT scans.

Ultrasonography and voiding cystoureterography are recommended in patients suspected of having reflux disease. Radionuclide-voiding cystography may also detect reflux disease.

Differential Diagnosis

The acute cystitis-urethritis syndrome in women must be differentiated from herpes simplex infection, C trachomatis infection, and vaginitis. A pelvic examination should be performed to detect genital herpes simplex virus infection. C trachomatis infection has a more gradual onset of dysuria and should be suspected in sexually active women with a recent new sexual partner. Hematuria is usually absent in Chlamydia infection. A diagnosis of Chlamydia infection is confirmed by rapid diagnostic techniques using commercially available kits. Vaginitis is a common cause of dysuria, but patients usually complain of external dysuria, which begins shortly after the onset of micturition and results from urine contact with inflamed vaginal labia. Pyuria and hematuria are usually absent in vaginitis. The presence of gross or microhematuria may occur in association with genitourinary-tract neoplasms, urolithiasis, or structural abnormalities of the genitourinary tract system. Patients at opposite extremes of age groups may not present with symptoms that are typical of UTI. In children < 2 years of age, failure to thrive, vomiting, and fever may be the major manifestations. Elderly patients with pyelonephritis may present with fever, hypotension, and sepsis syndrome without symptoms of a urinary tract infection. Among elderly patients with gram-negative bacteremia without an obvious source, a UTI should be considered.

Complications

Uncommon or rare complications of UTI include acute papillary necrosis, perinephric or intrarenal abscess, emphysematous pyelonephritis, or xanthogranulomatous pyelonephritis. When present, acute papillary necrosis is most common in diabetic dehydrated patients with pyelonephritis and is characterized by diminished renal function and sloughing of renal papilla. The most common predisposing factors for perinephric abscess are renal stones and diabetes mellitus, and perinephric abscess usually occurs as the result of obstruction or, less commonly, bacteremia. The infecting organisms for perinephric abscess are usually gram-negative bacilli or S aureus, if the cause is bacteremia. Polymicrobial infection is present in ~ 25% of cases of perinephric abscess. Intrarenal abscess usually occurs as the result of S aureus bacteremia. Perinephric or intrarenal abscess should be considered in patients with pyelonephritis who have been ill for ≥ 2 weeks and in those who have a slow response or no response to effective antimicrobial therapy. Emphysematous pyelonephritis is a rare complication of pyelonephritis and most often occurs in elderly diabetics. This condition should be suspected in patients with rapidly progressive infections with sepsis syndrome that respond poorly to antimicrobial therapy. Xanthogranulomatous pyelonephritis is a rare form of chronic renal infection with massive enlargement of the kidney, in which the renal parenchyma is replaced by inflammatory granulomatous tissue, which is characterized by lipid-laden foamy macrophages. Renal calculus formation and obstruction are common. P mirabilis is occasionally recovered from urine culture.

Antimicrobial Therapy

  1. Acute uncomplicated cystitis-urethritis in women.
  2. Singe-dose therapy.Single-dose antimicrobial therapy results in cure rates ranging from 65–100%, depending on the antimicrobial agent administered. High cure rates of 85–95% may be achieved after therapy with a fluoroquinolone, such as ciprofloxacin, ofloxacin, or levofloxacin, or with trimethoprim-sulfamethoxazole. β-Lactam therapy is less effective, possibly because of persistence of microorganisms in the periurethral and perirectal area or because of resistance of microorganisms to β-lactams. The advantages of single-dose therapy are high compliance and reduced adverse effects. The disadvantages include higher failure rates than longer courses of therapy, and the higher failure rates may be the result of undetected upper-tract infection that is inadequately treated with single-dose therapy. Patients who fail single-dose therapy with trimethoprim-sulfamethoxazole or a fluoroquinolone should be evaluated for possible upper-tract infection. Women with postcoital cystitis-urethritis are good candidates for single-dose therapy.
  3. Three-day therapy.Numerous studies have demonstrated that 3 days of antimicrobial therapy are as effective as 7–10 days of therapy, and 3-day therapy should be considered as standard therapy. Trimethoprim-sulfamethoxazole or a fluoroquinolone should be considered as the agent of choice for 3-day therapy. With a susceptible microorganism, 3 days of β-lactam therapy results in cure rates similar to those after treatment with trimethoprim-sulfamethoxazole or a fluoroquinolone. However, therapy with ampicillin or amoxicillin may be less effective than a second- or third-generation oral cephalosporin because of the relatively high frequency of ampicillin-resistant E coliin community-acquired UTIs. Sexually active females with the gradual onset of symptoms or recent change in a sexual partner should be considered to have C trachomatis infection and should be treated as shown in Box 16-2.

There are currently insufficient data to recommend shorter-course therapy (single-dose or 3-day treatment) in men or children with UTIs. These patients are at higher risk of structural abnormalities or upper tract infection, and therapy should be administered for 7–10 days. Follow-up urine cultures should be obtained 1–2 weeks after completion of treatment to detect relapses or persistence.

  1. Acute pyelonephritis.Patients with severe infections, such as those with nausea, vomiting, and hypotension, should be hospitalized. Others with mild to moderate infection may be treated as outpatients, provided that they are compliant and are able to tolerate oral antimicrobial therapy. Antimicrobial therapy is initially empiric and should be modified appropriately based on the results of cultures and susceptibilities. Effective therapy results in defervescence of fever and other symptoms, usually within 48 h after onset of treatment. Failure to respond may be the result of resistant microorganisms or the presence of perinephric or intrarenal abscess or persistence of infection in polycystic renal disease. Antimicrobial therapy of pyelonephritis should be administered for 14 days. Patients with acute pyelonephritis should have an ultrasound examination to exclude obstruction or stones. A follow-up urine culture should be obtained 1–2 weeks after completion of therapy. In hospitalized patients, parenteral therapy may be changed to orally administered therapy when patients improve and are able to tolerate oral therapy.
  1. Asymptomatic bacteriuria.Children should be treated with antimicrobial therapy as described for those with symptomatic infection, as shown in Box 16-2. Aside from pregnant women, adults, especially the elderly, do not benefit from antimicrobial therapy.
  2. Pregnancy.The rationale for antimicrobial therapy in these patients is described above. The goal of treatment is to maintain sterile urine throughout pregnancy. The antimicrobial regimens are shown in Box 16-2. Single-dose therapy has not been adequately studied in these patients. Three-day therapy may be as effective as seven-day treatment but there are relatively few published studies with three-day treatment of asymptomatic bacteriuria in pregnant women. Follow-up urine cultures should be obtained 1–2 weeks after completion of therapy and at monthly intervals throughout the duration of pregnancy. If bacteriuria recurs, the patient should be re-treated, and, if multiple relapses occur, suppressive therapy should be administered throughout gestation, and radiologic evaluation may be performed after delivery.
  3. Asymptomatic bacteriuria after urinary tract instrumentation.The majority of patients with previously sterile urine who have persistent bacteriuria after instrumentation or removal of a urinary catheter should receive 3 days of antimicrobial therapy. The selection of therapy should be based on the results of culture and susceptibility tests.
  4. Relapsing UTI.Relapse usually occurs within 1–2 weeks after completion of therapy and is most often associated with upper tract infection, structural abnormalities including stones, or chronic prostatitis. Bacteriologic eradication in patients with obstruction or calculi depends on surgical correction of obstruction or removal of stones. The treatment of relapsing chronic prostatitis is discussed below. Patients with upper tract infection who relapse after short-course therapy should be retreated for ≥ 2 weeks. A 6-week course of therapy should be administered to those patients that relapse after a 2-week course. Some women will continue to experience relapse with no obvious cause or despite surgical correction of structural abnormalities. If relapse occurs after a 6-week course, in selected patients who have continuous symptoms of UTI, a treatment course of 6–12 months should be considered. Patients selected for long-term therapy include children, adults with continuous symptoms, or adults at high risk of progressive renal damage or those patients with obstructions that are not amenable to surgery. Asymptomatic adults with bacteriuria without obstruction should not receive long-term therapy.
  1. Reinfection.Women with infrequent reinfection (≤ 2–3 times/year) should be treated with short-course antimicrobial therapy as if each UTI were a new, discrete episode. Single-dose self-administered therapy taken after sexual intercourse is usually effective to decrease the frequency of UTI related to sexual activity. In some women with frequent lower-tract reinfection, no precipitating event is apparent. In these patients with symptomatic, frequent reinfection, long-term antimicrobial therapy is warranted. If reinfection occurs during treatment, urine culture and sensitivity should be obtained, and the prophylactic regimen should be changed based on the results.
  2. Prostatitis.
  3. Acute prostatitis.Antimicrobial therapy of acute prostatitis in young men (< 35 years of age) should include agents that are effective against N gonorrhoeaeand C trachomatis (Box 16-2). Patients older than 35 years usually have infection caused by members of the Enterobacteriaceae. Studies suggest that the relapse rate or development of chronic prostatitis may be higher in patients with acute prostatitis who are treated for < 4 weeks with antimicrobial therapy. Prostatic abscess usually requires drainage; cure with antimicrobial therapy alone is uncommon.
  4. Chronic prostatitis.The selection of an antimicrobial agent should be based on culture and sensitivity results. Cure is difficult to achieve, and relapses are common. Therapy with trimethoprim-sulfamethoxazole or a fluoroquinolone results in higher drug concentrations in prostate tissue and superior cure rates compared with therapy with a β-lactam. The presence of prostatic calcification or stones is associated with a high failure rate. Chronic suppressive therapy, usually with trimethoprim-sulfamethoxazole or a fluoroquinolone or trimethoprim alone, may control symptoms of chronic bacterial prostatitis in patients who relapse after 1–3 months of antimicrobial therapy. Transurethral resection of the prostate, together with antimicrobial therapy, may be necessary to cure patients with chronic prostatitis and an enlarged prostate with or without calcifications, who remain symptomatic despite antimicrobial therapy.
  5. Perinephric or intrarenal abscess.Patients with perinephric or intrarenal abscess usually require open drainage or ultrasound or CT-guided drainage. Patients with polycystic renal disease who fail to respond to antimicrobial therapy may require aspiration or surgical drainage of infected cysts. Patients with emphysematous pyelonephritis should undergo immediate nephrectomy because of the high mortality in patients treated with medical therapy alone. Patients with xanthogranulomatous pyelonephritis require nephrectomy.

BOX 16-2 Empiric Antimicrobial Therapy of Urinary Tract Infections

Condition

First Choice

Second Choice

Women and girls, ≥2 years of age, with acute uncomplicated cystitis and/or urethritis

· TMP/SMX, 1 double strength OR TMP, 8-12 mg/kg, plus SMX, 40-60 mg/kg twice daily for 3 d
OR

· In patients 15 years of age or older, a fluoroquinolone1 for 3 d

· Amoxicillin or amoxicillin/clavulanate, 500 mg or 45 mg/kg of amoxicillin three times daily for 3 d
OR

· An oral cephalosporin1 for 3 d
OR

· TMP/SMX, 1 double-strength, single dose2
OR

· A fluoroquinolone1 single dose2

Women with risk factors for sexually transmitted diseases

· Doxycycline, 100 mg twice daily for 7 d

· Azithromycin, 1 g single dose

Adults not hospitalized with acute pyelonephritis

· Fluoroquinolone1 orally for 14 d

· Amoxicillin/clavulanate, 500 mg orally for 14 d
OR

· Second-or third-generation oral cephalosporin1 for 14 d

Children or hospitalized adults with acute pyelonephritis

· Ampicillin, 1 g IV3 or 25-50 mg/kg every 4 h
OR

· Ampicillin, 25-50 mg/kg every 6 h plus gentamicin or tobramycin, 5 mg/kg/d in divided or single daily dose for 14 d
OR

· A third-generation cephalosporin1 IV3 for 14 d
OR

· In patients 15 years of age or older, a fluoroquinolone1 IV3 or orally for 14 d

· Ticarcillin/clavulanate, 3.1 g or 50-75 mg/kg of ticarcillin component every 6 h
OR

· Piperacillin/tazobactam, 3.375 g IV3 every 6 h for 14 d or 80 mg/kg every 8 h or piperacilllin component
OR

· Aztreonam, 1 g IV3 every 8 h for 14 d or 30 mg/kg every 6–8 h

Asymptomatic bacteriuria
Children

· Treat with regimen for symptomatic cystitis-urethritis for 7 d

 

Pregnancy

· Amoxicillin (dosage above) or oral cephalosporin,1or TMP/SMX (dosage above) or TMP, 100 mg orally twice daily, or nitrofurantoin, 100 mg orally twice daily for 7 days. Discontinue sulfa 2 wk before delivery. Avoid fluoroquinolone or tetracycline use.

Adults, elderly Caused by urinary tract instrumentation

· No treatment necessary

· Choice of therapy depends on results of culture and antimicrobial sensitivity. Treat for 3 d

Acute prostatitis Less than 35 years of age

· Fluoroquinolone1 for 7 d

· Ceftriaxone, 125 mg IM single dose, or other FDA-approved cephalosporin1 plus either doxycycline, 100 mg orally twice daily for 7 d or azithromycin, 1 g orally as a single dose

Older than 35 years of age

· Fluoroquinolone1 or TMP/SMX, 1 DS orally twice daily for 4 wks

Chronic prostatitis

· Fluoroquinolone1 or TMP/SMX, 1 DS twice daily orally for 1-3 mo

Urinary catheter associated

· Aminoglycoside plus one of the following: a fluoroquinolone, a third-generation cephalosporin, piperacillin/tazobactam, or aztreonam for 7-14 d.4Dosages are as above.

1Dosage of fluoroquinolone or oral or parenteral cephalosporin depends upon specific drug selected for use.
2Single dose therapy not recommended for children 15 years of age or younger.
3Intravenous therapy may be changed to oral therapy with TMP/SMX or amoxicillin, amoxicillin/clavulanate, a cephalosporin, or a fluoroquinolone (see footnote 1) after initial satisfactory response and when culture results are available.
4Multiply resistant microorganisms are common; antimicrobial therapy may be adjusted based on results of susceptibility tests.

Prognosis

  1. Children.Children without obstruction or vesicoureteral reflux have an excellent prognosis. Uncorrected obstruction with infection may result in severe progressive renal disease. Reflux, together with infection, is associated with development of progressive renal scarring and, if untreated, may progress to arterial hypertension and end-stage renal disease. Eradication of bacteriuria may reduce the severity of reflux. Mild to moderate reflux may disappear spontaneously in older children over time, probably as a result of maturation of the vesicoureteral junction. Surgery may be necessary to correct severe persistent reflux disease.
  2. Adults.Prognosis of the large majority of adults with UTIs is excellent. Many women with UTIs had UTIs as children. A female who develops a UTI is more likely to develop subsequent infections than a woman who has had no prior UTI.

When associated with obstruction, infection may lead to progressive renal damage and failure. Recurrent infection in the absence of obstruction rarely, if ever, leads to progressive renal disease or arterial hypertension.

Prevention

Postcoital lower UTIs in females may usually be prevented by administration of a single dose of an antimicrobial agent after sexual intercourse (see above). Long-term prophylaxis should be considered for patients who have had frequent symptomatic relapses or recurrences of infection and are at risk of developing progressive renal damage, such as young children with vesicoureteral reflux or patients with obstruction or stones. For long-term prophylaxis, it is not usually necessary to administer the same dosage of an antimicrobial agent that has been used to treat symptomatic infection. For example, nightly administration of one single-strength trimethoprim-sulfamethoxazole or a lower dosage of a fluoroquinolone may suffice. Urine culture and antimicrobial sensitivity should be obtained periodically in patients who receive long-term prophylaxis, to monitor for development of resistance and persistence of bacteriuria. A change of antimicrobial therapy may be necessary in these patients.

NOSOCOMIALLY ACQUIRED URINARY TRACT INFECTIONS

Essentials of Diagnosis

  • Majority asymptomatic.
  • Fever, chills, possible suprapubic or flank pain.
  • Positive urine or blood culture for gram-negative bacilli; number of bacteria usually ≥ 100,000 colony forming units/mL of urine.

Urinary tract infection is the most common nosocomially acquired infection, accounting for ≥ 40% of all nosocomial infections. Of nosocomial UTIs, ≥ 80% are related to the use of a urethral catheter. The remaining cases are associated with other urinary tract instrumentations or surgery.

Catheter-associated UTI is one of the most common infections in acute care facilities and is the most common infection in chronic care settings. Before the development of closed catheter systems, the onset of bacteriuria in open draining systems occurred within 4 days after insertion of the catheter. With the closed-catheter system, the onset of bacteriuria is delayed to ≥ 30 days after insertion. All patients with a chronic indwelling urinary catheter will eventually develop bacteriuria.

Epidemiology and Microbiology

The duration of catheterization is the most important risk factor for the development of bacteriuria. The duration may be classified as short term (< 30 days) or long term (> 30 days).

Of patients with short-term catheterization, 15–30% will develop bacteriuria. E coli is the most common microorganism associated with short-term catheterization, accounting for ~ 25–30% of cases (Box 16-3). Other common microorganisms include P aeruginosa, Klebsiella spp., Proteus spp., and S epidermidis. Most cases of bacteriuria associated with short-term catheterization are caused by a single microorganism.

All patients with an indwelling urinary catheter for > 30 days will develop bacteriuria. New episodes of bacteriuria caused by different microorganisms occur commonly. In addition, some microorganisms may persist for weeks, months, or years. Polymicrobial bacteriuria occurs in ≥ 95% of patients with long-term catheterization. Providencia stuartii is one of the most common microorganisms that cause bacteriuria in patients with long-term catheterization and may persist for months and years.

Pathogenesis

In patients with a urinary catheter, microorganisms may enter the bladder through at least three mechanisms: (1) At the time of catheter insertion, (2) through the lumen of the catheter, or (3) along the catheter-urethral interface.

The insertion of the urinary catheter through the urethra may transport microorganisms located within the periurethral area into the bladder. The insertion results in bacteriuria in from < 1% in young healthy individuals to > 20% in elderly or hospitalized patients. Microorganisms may enter the drainage bag, multiply, persist in the film of urine within the bag and tubing, ascend the lumen of the tubing, and enter the bladder. The closed drainage system reduces the risk of intraluminal entry of microorganisms into the bladder. The most likely mechanism for the entry of microorganisms into the bladder is along the catheter-ureteral interface. Microorganisms in the periurethral area enter the space between the catheter and the urethral mucosa and ascend into the bladder. This route probably accounts for 80% of episodes of bacteriuric females and 30% of those bacteriurias that occur in males.

BOX 16-3 Microbiology of Nosocomially Acquired Urinary Tract Infection in Children or Adults

Catheter-Associated Short-Term (<30-d) Catheterization

More Frequent
Less Frequent

· Escherichia coli

· Other Enterobacteriaceae

· Pseudomonas spp.

· Staphylococcus epidermidis

Catheter-Associated Long-Term (>30 days) Catheterization

More frequent



Less frequent

· Providencia stuartii

· Pseudomonas spp.

· Escherichia coli

· Other Enterobacteriaceae

· Staphylococcus epidermidis

Once bacteria enter the urinary bladder, they multiply and maintain themselves primarily through the production of a biofilm, which covers and secures bacteria on the mucosal or catheter surface where they are protected from natural host defenses or from the activity of antimicrobial agents. Microorganisms may ascend the ureters to the kidneys. The presence of chronic bacteriuria in association with an indwelling urinary catheter may result in the formation of urolithiasis or acute and chronic infection including pyelonephritis. Risk factors that predispose to bacteriuria in patients with indwelling urinary catheters include the duration of catheterization, diabetes mellitus, female sex, and errors in catheter care.

Clinical Findings

  1. Signs and symptoms.The majority of patients with short-term catheterization and bacteriuria are asymptomatic. However, 25–30% of these will develop signs of UTI with fever, suprapubic pain, or flank pain. Men are more likely to develop bacteriuria than women. Bacteremia usually caused by coli occurs in < 5% of patients with short-term catheterization. Patients with long-term catheterization may develop symptoms of UTI similar to those of patients with short-term catheterization.
  1. Laboratory findings.The diagnosis of bacteriuria is made by performing quantitative urine cultures on a specimen obtained by using aseptic techniques from the urinary bag. In most instances, quantitative culture yields > 100,000 colonies of bacteria/mL of urine.

Differential Diagnosis

Among patients with indwelling urinary catheters who develop fever and signs of infection, the urinary tract should be considered the most likely source of bacteremia. However, many patients with a chronic indwelling urinary catheter are at risk of bacteremia from other sources such as decubitus ulcer, aspiration pneumonia, intra-abdominal infections, and other conditions that are common in chronically ill, elderly patients.

Complications

In addition, these patients may develop complications associated with catheter obstruction, stone formation, renal failure, or chronic pyelonephritis. Like patients with short-term catheterization, bacteremia may occur and is usually caused by E coli but also may be caused by P stuartii or other members of the Enterobacteriaceae..

Obstruction is the result of catheter plugging caused by a matrix composed of protein, bacteria, glycocalyx, and crystals. P mirabilis is the most common microorganism that causes catheter obstruction and stone formation in patients with long-term catheterization. Chronic pyelonephritis is related to the duration of catheterization. Chronic renal failure may occur, resulting from a combination of factors that includes chronic pyelonephritis, stone formation, and catheter obstruction.

Therapy

The use of antimicrobial therapy may delay the onset but does not prevent bacteriuria in patients with an indwelling urinary catheter. Moreover, long-term administration of antimicrobial agents to these patients results in selection of resistant microorganisms in the urine. Asymptomatic bacteriuria in patients with an indwelling urinary catheter should not be treated with antimicrobial therapy. For most patients, if bacteriuria persists after removal of the catheter, short-term (3-day) antimicrobial therapy is recommended (Box 16-2). Patients who develop symptoms of infection that are associated with an indwelling urinary catheter should receive 7–10 days of antimicrobial therapy with specific activity in vitro against microorganisms recovered from blood or urine cultures.

Asymptomatic candiduria develops frequently in patients with long-term catheterization, especially among patients who have received antimicrobial therapy. Some patients may develop complications of candiduria, which include catheter obstruction, fungus ball formation, or invasion of the bladder wall or kidney parenchyma. In asymptomatic patients, removal of the catheter usually results in the disappearance of candiduria. For patients who develop complications, change of an obstructed urinary catheter, cystoscopic removal of a fungus ball, bladder irrigation with amphotericin B, or systemic therapy with orally or parenterally administered anti-Candida therapy may be necessary.

Prognosis

The prognosis for bacteriuria in patients with short-term catheterization is excellent after removal of the catheter. The frequency of bacteremia originating from the urinary tract in patients with short-term catheterization is < 5%, and the mortality related to bacteremia from nosocomial bacteriuria in these patients is < 15%. Most deaths are related to severe underlying disease.

In patients with long-term urinary catheters, bacteriuria will persist for as long as the catheter is in place and may persist even after catheter removal, despite administration of antimicrobial therapy. The urinary tract is the source of the majority of febrile episodes of bacteremia in patients with long-term urinary catheters. The mortality during febrile periods that originate from a urinary source in patients with long-term catheters is 60-fold that of afebrile patients with chronic indwelling urinary catheters.

Prevention

Prevention of bacteriuria may be considered as follows: avoidance of long-term urinary catheterization, prevention of bacteriuria once a urinary catheter is inserted, prevention of complications of bacteriuria, and prevention of patient-to-patient transmission.

  1. Avoidance of urinary catheterization.Methods such as biofeedback, patient training for bladder-emptying techniques, and the use of special clothing, including adult diapers, may be effective in selected patients. Condom catheters have been used in men and probably reduce the risk of bacteriuria. Intermittent self or assisted catheterization delays the onset of bacteriuria and may reduce the frequency of bacteremia, febrile episodes, stone formation, and renal disease. Suprapubic catheterization may reduce the incidence of bacteriuria and ureteral strictures.
  2. Prevention of bacteriuria.Once a urinary catheter is inserted, the major methods for prevention of bacteriuria are to maintain a closed catheter system and to remove the catheter as soon as possible. Irrigation of the catheter and bladder with antimicrobial agents has not been effective in preventing bacteriuria. The use of silver- or antibiotic-coated or -impregnated urinary catheters has been investigated.


Conflicting results have been published, and more data are necessary to assess the efficacy of silver-coated urinary catheters in reducing the risk of bacteriuria. Antimicrobial agents should not be administered to patients with long-term catheterization, to prevent bacteriuria. Bacteriuria will occur despite antimicrobial therapy. Microorganisms will emerge that are resistant, and therapy is expensive. Methanamine is an antibacterial agent that forms formaldehyde in acidic urine and may be useful to reduce bacteriuria in patients with intermittent catheterization.

  1. Prevention of complications.Blood and urine cultures should be obtained during febrile episodes, and antimicrobial therapy should be administered. Antimicrobial therapy should not be administered as prophylaxis for febrile episodes to patients with bacteriuria.
  2. Prevention of patient-to-patient transfer.Nosocomial microorganisms reside on the skin and in the periurethral area of patients with indwelling urinary catheters. Patient-to-patient transmission may occur as the result of contamination of the hands of medical personnel who may then transmit these microorganisms to patients. Good hand-washing techniques and wound and skin precautions should be observed in patients with chronic urinary catheters. Education regarding good catheter hygiene and care of the closed catheter system is important for patients, family, and health care personnel. Outbreaks of multiresistant nosocomial catheter-associated urinary tract infections may occur. Hospital infection control should have adequate surveillance mechanisms in place and procedures to control and eradicate outbreaks, should they occur.

REFERENCES

Johnson J, Stamm W: Diagnosis and treatment of acute urinary tract infection. Infect Dis Clin North Am 1987;1:773.

Sobel JD, Kaye D: Urinary Tract Infections. In Mandel et al: Principles and Practices of Infectious Diseases, 4th ed. Churchill Livingstone, 1995.

Warren JW: Nosocomial urinary tract infections. In Mandel et al: Principles and Practices of Infectious Diseases, 4th ed. Churchill Livingstone, 1995.