Approach Considerations
The American Academy of Pediatrics (AAP) criteria for the diagnosis of urinary tract infection (UTI) in children 2-24 months are the presence of pyuria and/or bacteriuria on urinalysis and the presence of at least 50,000 colony-forming units (CFU) per mL of a uropathogen from the quantitative culture of a properly collected urine specimen. In neonates younger than 2 months of age, criteria include the presence of lower amounts of a single pathogen (10,000-50,000 CFU/mL). [1]
Due to concerns over urinalysis sensitivity in young infants, a study collected urinalysis results on a cross-sectional sample of 276 infants < 3 months of age with bacteremic UTI from 11 hospital systems. The study concluded that in young infants with bacteremic UTI, urinalysis sensitivity in infants with UTI in general is higher than what has been previously reported. [14]
Urine specimen collection
A midstream, clean-catch specimen may be obtained from children who have urinary control. In the infant or child unable to void on request, the specimen for culture should be obtained by suprapubic aspiration or urethral catheterization.
Suprapubic aspiration is also the method of choice for obtaining urine from uncircumcised boys with a redundant or tight foreskin, from girls with tight labial adhesions, and from children of either sex with clinically significant periurethral irritation.
Culture of a urine specimen from a sterile bag attached to the perineal area has a false-positive rate so high that this method of urine collection is not suitable for diagnosing UTI. However, a culture of a urine specimen from a sterile bag that shows no growth is strong evidence that UTI is absent. [1]
Urine dipstick test
In a study of 6394 febrile infants aged 1-90 days, Glissmeyer and colleagues found evidence that urine dipstick testing alone may provide an adequate initial UTI screen, comparing well in terms of positive predictive value and specificity with urine microscopy alone or both tests combined. [15, 16] UTI was diagnosed in 770 (12%) of the study’s infants. Although the different screens each had a negative predictive value of more than 98%, the dipstick screen had a higher positive predictive value (66.8%) than did the combined test (51.2%) or microscopy alone (58.6%). [15, 16]
The dipstick test by itself also had a higher specificity (93.8%) compared with the combined test (87.6%) or microscopy (91.3%), although it did have a lower sensitivity than the combined test (90.8% vs 94.7%, respectively.) [15, 16]
Urinalysis
Urinalysis alone is not sufficient for diagnosing UTI. Children with unexplained fever or voiding symptoms may have positive urinary cultures even when abnormal findings are not evident on dipstick testing and complete urinalysis. [17, 18, 19, 20, 21, 22, 23] However, urinalysis can help in identifying febrile children who should receive antibacterial treatment while culture results from a properly collected urine specimen are pending. [24]
A study by Lunn et al supports the use of automated microscopy for screening urine samples for culture in children. [25] In 280 urine samples collected from 263 pediatric patients, automated microscopy performed comparably to urine dipstick testing in the diagnosis of UTI; automated microscopy had better specificity and likelihood ratios than dipstick testing, but it had slightly lower sensitivity.
Blood studies
Hematologic studies do not tend to help in the diagnosis of UTIs, although they should be obtained in patients who appear ill. Obtain a complete blood count (CBC) and basic metabolic panel for children with a presumptive diagnosis of pyelonephritis. Perform blood cultures in febrile infants and older patients who are clinically ill, toxic, or severely febrile.
Evaluation of renal function
Renal function can be measured by serum creatinine and blood urea nitrogen (BUN) levels; both may be elevated in severe disease. Electrolyte abnormalities may be present. Procalcitonin, a propeptide of calcitonin that has been found to be elevated in response to bacterial endotoxins, has shown promise in helping to diagnose pyelonephritis and early renal damage. [26, 27, 28]
Imaging studies
Imaging studies are not indicated for infants and children with a first episode of cystitis or for those with a first febrile UTI who meet the following criteria:
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Assured follow-up
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Prompt response to treatment (afebrile within 72 h)
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A normal voiding pattern (no dribbling)
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No abdominal mass
If imaging studies of the urinary tract are warranted, they should not be obtained until the diagnosis of UTI is confirmed. Febrile infants aged 2-24 months with UTIs should undergo renal and bladder ultrasonography. [1] Other indications for ultrasonography of the urinary tract after a febrile UTI in pediatric patients are as follows:
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Delayed or unsatisfactory response to treatment of a first febrile UTI
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An abdominal mass or abnormal voiding (dribbling of urine)
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Recurrence of febrile UTI after a satisfactory response to treatment
Finally, renal ultrasonography should be considered for any child with a first febrile UTI in whom good follow-up cannot be ensured.
Performance of voiding cystourethrography (VCUG) after a first febrile UTI may be indicated if renal and bladder ultrasonography reveal hydronephrosis, scarring, obstructive uropathy, or masses or if complex medical conditions are associated with the UTI. Informed consent and preferences of the patient’s parents or caregivers are considered.
Children who respond to treatment for a UTI but afterwards demonstrate an abnormal voiding pattern may need to undergo an evaluation for voiding dysfunction. This evaluation may include standard VCUG.
VCUG is also recommended after a second episode of febrile UTI. [1] There is some concern, however, that without VCUG after the first documented febrile UTI, some cases of significant reflux disease will be missed. [29]
The chart below details a management approach to febrile infants younger than 3 months with a temperature of more than 38°C.
Application of low-risk criteria for and approach to the febrile infant: A reasonable approach for treating febrile infants younger than 2 months who have a temperature of greater than 38°C.
Go to Urinary Tract Infection in Males, Cystitis in Females, and Radiographic Evaluation of the Pediatric Urinary Tract for complete information on these topics.
Urine Collection and Analysis
The criterion standard for obtaining urine specimens for culture in pediatric patients is suprapubic aspiration. [30] However, catheterization is the most commonly used technique in infants and younger children. Midstream clean-catch urine specimens are adequate for older children who can provide them. The presence of at least 50,000 CFU/mL of a uropathogen is the AAP definition for a UTI. [1]
Culture of a urine specimen from a sterile bag attached to the perineal area has a false-positive rate so high that this method of urine collection is not suitable for diagnosing UTI. However, a culture of a urine specimen from a sterile bag that shows no growth is strong evidence that UTI is absent. [1]
Along with a positive urine culture, urinalysis showing pyuria and/or bacteriuria is part of the criterion standard for the diagnosis of UTIs. [1] Positive dipstick readings for nitrite, leukocyte esterase, or blood may also suggest a UTI. Dipstick tests have sensitivities of approximately 85-90%. Microscopic examination of spun urine can evaluate for the presence of white blood cells (WBCs), red blood cells (RBCs), bacteria, casts, and skin contamination (eg, epithelial cells).
On a suprapubic aspirate, the presence of 5 or more WBCs per high-power field suggests an infection. The presence of 10 or more WBC/μL is also consistent with infection. [31, 32] Gram stain of unspun urine may reveal organisms. A hemacytometer measures cells per volume and has been found to be more sensitive and specific than standard microscopic examination. [31, 32] The combination of hemacytometer cell count and Gram stain has been shown in studies to have a sensitivity approaching 95%.
Approximately 10-20% of pediatric patients with UTIs have normal urinalysis results. Multiple organisms may be present in patients with structural abnormalities.
A study by Tzimenatos et al that included an analysis of data from 4147 febrile infants ≤60 days old reported that for the 289 infants with a UTI and colony counts ≥50 000 CFUs/mL, a positive urinalysis regardless of bacteremia showed sensitivities of 0.94; 1.00 with bacteremia; and 0.94 without bacteremia. Specificity in all groups was 0.91. [33]
Methods of urine collection and examination, as well as salient findings, are shown in Tables 1 and 2, below.
Table 1. Urinalysis for Presumptive Diagnosis of Urinary Tract Infection* (Open Table in a new window)
Method |
Findings |
Bright-field or phase-contrast microscopy of centrifuged urinary sediment |
Bacteria |
Gram stain of uncentrifuged or centrifuged urinary sediment |
Bacteria |
Nitrite and leukocyte esterase test |
Positive = UTI likely |
Nitrite test |
Positive = UTI probable |
Leukocyte esterase test |
Positive = UTI probable |
*Negative microscopic findings for bacteria do not rule out a UTI, nor do negative results of dipstick testing for nitrite and leukocyte esterase. False-negative nitrite readings are especially common in children. |
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Table 2. Quantitative Urine Culture for the Diagnosis of Urinary Tract Infection* (Open Table in a new window)
Method |
Finding |
Suprapubic aspiration |
If a UTI is present, bacteria are likely to be proliferating in bladder urine with growth of any organism except 2000-3000 CFU/mL coagulase-negative staphylococci. |
Catheterization in a girl or midstream, clean-void collection in a circumcised boy |
Febrile infants and children with UTI usually have >50,000 CFU/mL of a single urinary pathogen; however, UTI may be present with 10,000-50,000 CFU/mL of a single organism.* |
Midstream, clean-void collection in a girl or uncircumcised boy |
UTI is indicated when >100,000 CFU/mL of a single urinary pathogen is present in a symptomatic patient. Pyuria usually present. A UTI may be present with 10,000-50,000 CFU/mL of a single bacterium.* |
Any method in a girl or boy |
If the patient is asymptomatic, bacterial growth is usually >100,000 CFU/mL of the same organism on different days. If pyuria is absent, this result probably indicates colonization rather than infection. |
*Patients with urinary frequency (ie, decreased bladder incubation time) are those most likely to have bacteria proliferating in the urinary bladder in the presence of low colony counts. |
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Lab-based versus point-of-care urinalysis
In a large retrospective analysis of children with UTI, laboratory-based urinalysis was more sensitive than point-of-care urinalysis in diagnosing pediatric UTI. Point-of-care urinalysis had 82.5% sensitivity, 81.3% specificity, 33.9% positive predictive value, and 97.6% negative predictive value, whereas laboratory-based urinalysis had 89.1% sensitivity and a significantly higher negative predictive value (98.9%). Laboratory-based urinalysis, however, was less specific (76.1%) and had a lower positive predictive value (22.7%). [34, 35]
Ultrasonography
Ultrasonography of the urinary tract has replaced intravenous pyelography (IVP) as the imaging study of choice in children with UTI. The AAP Clinical Practice Guidelines recommend routine ultrasonography of the urinary tract after a first febrile UTI in children aged 2-24 months. [1] Ultrasonography in these cases seldom provides information that changes management, however.
The clinician's judgment should guide the decision regarding imaging studies, rather than a rigid rule. Urinary ultrasonography is safe, noninvasive study, and easy to perform. It is useful in excluding obstructive uropathy, as well as in identifying a solitary or ectopic kidney and, in some cases, moderate renal damage caused by pyelonephritis.
A study by Shaikh et al indicates that in children and adolescents with a first UTI, the risk of scarring is doubled in those with either an abnormal renal ultrasonographic finding or with both a fever of 39°C (102°F) or above and a causative organism other than Escherichia coli. The investigators found the predictive ability of a model based on these factors to be only 3-5% below that obtainable with models in which a blood draw and/or a voiding cystourethrogram (VCUG) are needed. The report was a meta-analysis of nine cohort studies, and included 1280 patients aged 18 years or younger. [36, 37] The study also indicated that the greatest risk factor for renal scarring is the presence of grade IV or V vesicoureteral reflux (VUR). Of the 199 patients in the study who had renal scarring, 100 had VUR, although only 4.1% of the 1280 patients had grade IV or V type.
Voiding Cystourethrography or Nuclear Cystography
Traditionally, VCUG has been recommended for infants and children after a first febrile UTI. This is based on assumptions that most upper UTIs occur because of urinary bladder infection and that vesicoureteral reflux (VUR) transfers bacteria in the bladder to the kidney. However, scintigraphic studies have shown that many children with pyelonephritis have no evidence of VUR. [1, 38]
VCUG is indicated if renal and bladder ultrasonography reveals hydronephrosis, scarring, or other findings that suggest either high-grade VUR or obstructive uropathy. VCUG should also be performed if a patient has a recurrence of a febrile UTI, even if previous ultrasonographic examination findings were unremarkable. [1]
VCUG and antibiotic prophylaxis
In theory, VCUG results could guide the use of antibacterial prophylaxis. However, data do not support the use of prophylaxis to prevent recurrent febrile UTI in infants with no VUR or with grade 1-4 VUR. [39] Consequently, the AAP no longer recommends the routine use of VCUG after the first UTI. [1]
This topic remains controversial. More definitive evidence on the benefit of antibiotic prophylaxis in children with VUR—and thus on the indications for VCUG in pediatric patients with UTI—is anticipated from the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) study, which is ongoing. [40]
Some clinicians recommend waiting 4-6 weeks after febrile UTI is treated to perform VCUG. If the child is given suppressive antibacterial treatment during this period, this recommendation is acceptable. However, studies have shown that the VCUG may be obtained within the first few days of treating febrile UTI if the voiding pattern has returned to its pre-UTI state. [41, 42, 43]
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Application of low-risk criteria for and approach to the febrile infant: A reasonable approach for treating febrile infants younger than 2 months who have a temperature of greater than 38°C.
Tables
- Table 1. Urinalysis for Presumptive Diagnosis of Urinary Tract Infection*
- Table 2. Quantitative Urine Culture for the Diagnosis of Urinary Tract Infection*
- Table 3. Antibiotic Agents for Parenteral Treatment of a Urinary Tract Infection
- Table 4. Antibiotic Agents for the Oral Treatment of Urinary Tract Infection
- Table 5. Antibiotic Agents to Prevent Reinfection
Method |
Findings |
Bright-field or phase-contrast microscopy of centrifuged urinary sediment |
Bacteria |
Gram stain of uncentrifuged or centrifuged urinary sediment |
Bacteria |
Nitrite and leukocyte esterase test |
Positive = UTI likely |
Nitrite test |
Positive = UTI probable |
Leukocyte esterase test |
Positive = UTI probable |
*Negative microscopic findings for bacteria do not rule out a UTI, nor do negative results of dipstick testing for nitrite and leukocyte esterase. False-negative nitrite readings are especially common in children. |
|
Method |
Finding |
Suprapubic aspiration |
If a UTI is present, bacteria are likely to be proliferating in bladder urine with growth of any organism except 2000-3000 CFU/mL coagulase-negative staphylococci. |
Catheterization in a girl or midstream, clean-void collection in a circumcised boy |
Febrile infants and children with UTI usually have >50,000 CFU/mL of a single urinary pathogen; however, UTI may be present with 10,000-50,000 CFU/mL of a single organism.* |
Midstream, clean-void collection in a girl or uncircumcised boy |
UTI is indicated when >100,000 CFU/mL of a single urinary pathogen is present in a symptomatic patient. Pyuria usually present. A UTI may be present with 10,000-50,000 CFU/mL of a single bacterium.* |
Any method in a girl or boy |
If the patient is asymptomatic, bacterial growth is usually >100,000 CFU/mL of the same organism on different days. If pyuria is absent, this result probably indicates colonization rather than infection. |
*Patients with urinary frequency (ie, decreased bladder incubation time) are those most likely to have bacteria proliferating in the urinary bladder in the presence of low colony counts. |
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Drug |
Dosage and Route |
Comment |
Ceftriaxone |
50-75 mg/kg/day IV/IM as a single dose or divided q12h |
Do not use in infants < 6 wk of age; parenteral antibiotic with long half-life; may displace bilirubin from albumin |
Cefotaxime |
150 mg/kg/day IV/IM divided q6-8h |
Safe to use in infants < 6 wk of age; used with ampicillin in infants aged 2-8 wk |
| Ceftolozane/tazobactam | 30 mg/kg IV q8h x7-14 days | Indicated for complicated UTIs approved in children from birth and older; CrCl must be above 50 mL/min/1.73 m2 |
Ampicillin |
100 mg/kg/day IV/IM divided q8h |
Used with gentamicin in neonates < 2 wk of age; for enterococci and patients allergic to cephalosporins |
Gentamicin |
Term neonates < 7 days: 3.5-5 mg/kg/dose IV q24h Infants and children < 5 years: 2.5 mg/kg/dose IV q8h or single daily dosing with normal renal function of 5-7.5 mg/kg/dose IV q24h Children ≥5 y: 2-2.5 mg/kg/dose IV q8h or single daily dosing with normal renal function of 5-7.5 mg/kg/dose IV q24h |
Monitor blood levels and kidney function if therapy extends >48 h |
Note: CrCl = creatinine clearance; IM = intramuscular; IV = intravenous; q = every; UTI = urinary tract infection. |
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Protocol |
Daily Dosage |
Sulfamethoxazole and trimethoprim (SMZ-TMP) |
30-60 mg/kg SMZ, 6-12 mg/kg TMP divided q12h |
Amoxicillin and clavulanic acid |
20-40 mg/kg divided q8h |
Cephalexin |
50-100 mg/kg divided q6h |
Cefixime |
8 mg/kg q24h |
Cefpodoxime |
10 mg/kg divided q12h |
Nitrofurantoin* |
5-7 mg/kg divided q6h |
*Nitrofurantoin may be used to treat cystitis. It is not suitable for the treatment of pyelonephritis, because of its limited tissue penetration. |
|
Agent |
Single Daily Dose |
Nitrofurantoin * |
1-2 mg/kg PO |
Sulfamethoxazole and trimethoprim (SMZ-TMP) * |
5-10 mg/kg SMZ, 1-2 mg/kg TMP PO |
Trimethoprim |
1-2 mg/kg PO |
*Do not use nitrofurantoin or sulfa drugs in infants younger than 6 weeks. Reduced doses of an oral first-generation cephalosporin, such as cephalexin at 10 mg/kg, may be used until the child reaches age 6 weeks. Ampicillin or amoxicillin are not recommended because of the high incidence of resistant E coli. |
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