A Clinical guide to pediatric infectious disease

10

Urinary Tract Infections

The diagnosis of pediatric urinary tract infection is important because pediatric urinary tract infection can be a manifestation of underlying urinary tract abnormalities. Failure to recognize and appropriately manage these abnormalities may lead to recurrent urinary tract infection, renal scarring, and long-term alterations in renal function.

Etiology

Pediatric urinary tract infection begins with colonization of the periurethral area with gastrointestinal bacteria. These bacteria may then ascend into the bladder, kidneys, or both. A variety of virulence factors may promote infection with certain bacterial isolates. Escherichia coli organisms, a primary cause of urinary tract infection, have a variety of adhesive molecules that facilitate binding to uroepithelial cells. These “pili” function as ladders that enable the bacteria to ascend from the periurethral area into the urinary tract.

Host factors may also play a role in the development of complicated urinary tract infection. Ascension of bacteria from the bladder into the renal parenchyma may be facilitated by vesicoureteral reflux (VUR). VUR is a congenital condition resulting from a defect in the ureterovesical junction. This defect affects closure of the ureter, which then allows retrograde flow of urine from the bladder into the kidneys. Infection with E. coli accounts for most urinary tract infections. Less common pathogens include enterococcus and other enterics such as Proteus species.

Presentation

In adults, the diagnosis of urinary tract infection is often associated with signs such as increased frequency or dysuria; these symptoms may be lacking in young children. A urinary tract infection needs to be considered in any young child presenting with fever. Studies have shown that the rate of urinary tract infection in infants

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with unexplained fever is between 5% and 10%. An uncircumcised male with an unexplained fever of greater than 39°C (102.2°F) has been reported as having a 35% chance of having a urinary tract infection.

Diagnosis

Paramount to the diagnosis of urinary tract infection and any subsequent radiographic investigation is proper collection and examination of the urine. A bagged specimen is not appropriate for the diagnosis of urinary tract infection because it is easily contaminated by bacteria. In infants who are in diapers, an “in-and-out” catheterization is usually required. In toilet-trained children, a clean-catch specimen may be adequate if the child can be adequately prepped. Urine specimens that cannot be processed at once should be refrigerated at 4°C. Urine kept at room temperature, for even a short period of time, can alter the results of leukocyte esterase and nitrate tests routinely done on dipstick examination.

Analysis of a properly obtained urine specimen can provide a clue to the presence of infection. However, there remains considerable debate about the best test to perform. Urine dipstick for nitrate and leukocyte esterase, evaluation for bacteruria, and the presence of pyuria have all been used as screening tests for urinary tract infections.

Nitrate detected by dipstick is positive in 50% of children with urinary tract infection. This relatively low figure may be related to the fact that the test requires bacteria to remain in the bladder for several hours, a condition that is less likely in children.

The evaluation for pyuria is complicated by a variety of factors, including the precise number of white blood cells needed for presumptive diagnosis of infection and whether the urine specimen being evaluated is centrifuged before analysis. Hemocytometry is a method used to count white blood cells in body fluids such as spinal fluid and urine. In recent years, considerable study has been done on the use of hemocytometry in “enhanced urinalysis.” In this method, urine is obtained by catheter and evaluated as an uncentrifuged specimen. The enhanced urinalysis is considered positive if there are more than 10 white blood cells/mm3 and any bacteria on Gram stain. The sensitivity of this method is 85%, with a specificity of 99%. The drawback to enhanced urinalysis is that the equipment needed may not be readily available. The traditional standard urinalysis uses centrifuged specimens, with pyuria being defined as at least 5 white blood cells per high-power field and the presence of any bacteria. The sensitivity of this method is 65%, with 92% specificity.

In 1999, the American Academy of Pediatrics recommended dipstick evaluation, standard microscopy, and Gram stain as useful screens for urinary tract infection. Positive leukocyte esterase or nitrate on dipstick, greater than 5 white blood cells per high-power field on standard urinalysis, or a positive Gram stain of unspun urine is suggestive of urinary tract infection. These parameters continue to be evaluated, with some investigators commenting on the need to evaluate further the screening methods or even to eliminate urinalysis entirely. It should be understood

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that urine testing serves as a screen. A negative screen does not rule out urinary tract infection. Clinical correlation is always needed. In a febrile child who has a strong possibility of urinary tract infection, a negative urinalysis should be followed by a urine culture.

Use of Urine Culture

A urine culture is obtained by inoculating a culture media with a standard volume of urine, typically 0.01 mL. Colony forming units (CFUs) are then calculated by counting the number of colonies on the inoculated area and converting it to CFU/mL. Most children who have urinary tract infections have bacterial colony counts of more than 105 CFU/mL of urine. This cutoff valve was established through studies in adults, with few comparable studies having been performed in children. There have been published guidelines to redefine the criteria for pediatric patients correlated with a variety of techniques for urine collection. Bacterial colony counts of more than 105 CFU/mL of urine collected by the clean-catch method correlated with high likelihood of a urinary tract infection. For catheter-obtained specimens, 5 × 104 CFU/mL is considered significant. In children who have had urine obtained by suprapubic aspiration, most investigators believe that the presence of any gram-negative enteric organism qualifies as a urinary tract infection.

Diagnosis of Urinary Tract Infection

Collection

Likely urinary tract infection

a. Suprapubic

Any gram-negative organism

b. Clean voided

    Boy

>105 CFU/mL of urine

    Girl

>105 CFU/mL of urine

c. Catheter obtained

5 × 104 CFU/mL of urine

Management of Urinary Tract Infection

In children who are not toxic and can maintain hydration, oral antibiotics can be started. Traditional oral antibiotics for the treatment of urinary tract infection in children include amoxicillin, trimethoprim-sulfamethoxazole, and oral cephalosporins. The increasing resistance ofE. coli to amoxicillin has reduced empiric therapy with this antibiotic. The newer-generation oral cephalosporins, such as cefixime, cefdinir, and ceftibuten, have excellent gram-negative enteric bacteria coverage and can be useful in the treatment of resistant E. coli urinary tract infections. Nitrofurantoin has been used for the treatment of cystitis, although its failure to achieve good bloodstream concentrations has led to the recommendation that it should not be used to

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treat febrile infants or children with upper urinary tract involvement. The total duration of therapy for a urinary tract infection is variable, although patients typically receive 7 to 14 days of therapy.

Radiographic Evaluation after Urinary Tract Infection

Imaging of the infant and young child with a urinary tract infection is one of the fundamentals of pediatrics. Urinary tract infection in children can be a manifestation of underlying urinary tract abnormalities that need to be documented. The American Academy of Pediatrics recommends that imaging of the urinary tract be done for every child 2 months to 2 years of age after the first urinary tract infection, regardless of the sex of the child.

Renal Ultrasound

The use of ultrasound can document hydronephrosis and ureteral dilation secondary to obstruction. The American Academy of Pediatrics has recommended the use of renal ultrasonogram for young children after the first urinary tract infection. This test should be done promptly in young children, particularly those who do not respond quickly to antimicrobial therapy. Young boys are at particular risk for posterior ureteral valves, and ultrasonography can be used to document quickly this malformation and the presence of accompanying hydronephrosis. Recently, the use of ultrasonography has been questioned by a variety of investigators. In a recent study of more than 300 children with urinary tract infection, ultrasound results were normal in almost 90% of cases; those that were abnormal did not modify patient management.

Cystourethrography

Voiding cystourethrography (VCUG) is still considered a useful test. The VCUG is performed by placing a catheter through the urethra into the bladder and instilling an iodinated contrast. Although this test is uncomfortable for the patient, it is the only method for diagnosing VUR. VUR is graded according to an international grading system. Scores increase with increasing ureteral dilation and progressive filling of the upper urinary tracts. VUR is identified in up to 50% of children who are evaluated after the first documented urinary tract infection.

The traditional recommendation was to obtain the VCUG about 4 weeks after the diagnosis of urinary tract infection. The logic for this recommendation was that acute infection and the acute inflammatory state of the upper urinary tract system would lead to a transient reflux. The current thinking regarding VUR is that it is a primary congenital phenomenon and not related to infection. For this reason, many clinicians obtain the VCUG on a more urgent basis after documentation of urine sterilization.

TABLE 10.1. Pediatric Urinary Tract Infection

Treatment

1. Parental

Cefotaxime (Claforan), 100–200 mg/kg/d divided q8h
  Ceftriaxone (Rocephin), 50–75 mg/kg/d divided q12
  Ampicillin (if enterococcus is a possibility), 100–200 mg/kg/d in 4 divided doses

2. Oral
   Amoxicillin, 40mg/kg/d in 3 divided doses
   Trimethoprim-sulfamethoxazole (Bactrim), 8–10mg/kg/d of trimethoprim component divided q12h
   Cephalexin (Keflex), 25–50 mg/kg/d in 4 divided doses
   Cefpodoxime (Vantin), 10mg/kg/d divided q12–24h

Imaging

1. Renal ultrasound

2. Voiding cystourethrogram

3. DMSA scanning

Prophylaxis

1. Nitrofurantoin (Furadantin), 1–2 mg/kg/dose PO qhs; maximum dose, 100 mg

2. Trimethoprim-sulfamethoxazole (Bactrim), 2–4 mg/kg/day PO qd

DMSA, dimercaptosuccinic acid.

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Renal Scintigraphy

Another study available to pediatricians for the evaluation of urinary tract infection is renal scintigraphy. Dimercaptosuccinic acid (DMSA) is attached to technetium and then infused into a patient. This compound localizes in renal tubules and can be used to diagnose acute pyelonephritis (sensitivity about 90%). DMSA scan can also be used to assess renal scarring months after acute infection. This test is useful if the diagnosis of pyelonephritis is in doubt or as a tool to follow patients with high-grade VUR and chronic infections.

Management of Vesicoureteral Reflux

Most infants with documented vesicoureteral reflux ultimately outgrow this condition. Reflux of sterile urine is not thought to cause renal damage; thus, antibiotic prophylaxis is given to prevent recurrent infection and the continuing reflux of infected urine, which may cause renal scarring. Prophylaxis with either trimethoprim-sulfamethoxazole or nitrofurantoin is frequently used. It should be remembered that breakthrough infections are always possible because of either noncompliance or the acquisition of resistant organisms not covered by the antibiotics being used for prophylaxis. A febrile illness in a child receiving prophylaxis for a urinary tract infection always warrants urinalysis and urine culture as part of the evaluation.

A summary of the diagnosis, treatment, and subsequent imaging can be seen in Table 10.1.

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Selected Readings

American Academy of Pediatrics. Committee of Quality Improvement. Subcommittee of Urinary Tract Infection. Practice parameter on the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics 1999;103(4 Pt. 1):843–852.

Armengol CE, Hendley O, Schlager TA. Should we abandon standard microscopy when screening for urinary tract infections in young children? Pediatr Infect Dis J 2001;20(12):1176–117.

Hoberman A, Wald ER, Reynolds EA, et al. Is urine culture necessary to rule out urinary tract infection in young febrile children. Pediatr Infect Dis J 1996;15(4):304–309.

McDonald A, Scranton M, Gillespie R, et al. Voiding cystourethrogram and urinary tract infections: how long to wait? Pediatrics2000;105(4): E50.