Urinary Tract Infection (UTI) in Children

Urinary tract infections in children are a marker of possible urinary tract abnormalities (eg, obstruction, neurogenic bladder Neurogenic bladder Congenital urinary bladder anomalies often occur without other genitourinary abnormalities. They may cause infection, retention, incontinence, and reflux. Symptomatic anomalies may require surgery... read more , ureteral duplication Ureter duplication anomalies Ureteral anomalies frequently occur with renal anomalies but may occur independently. Complications include Obstruction, vesicoureteral reflux, urinary tract infections, and urinary calculus... read more ); these abnormalities are particularly likely to result in recurrent infection if vesicoureteral reflux Vesicoureteral Reflux (VUR) Vesicoureteral reflux is retrograde passage of urine from the bladder back into the ureter and sometimes also into the renal collecting system, depending on severity. Reflux predisposes to urinary... read more (VUR) is present. About 20 to 30% of infants and children age 12 to 36 months with UTI have VUR. The younger the child at the first UTI, the higher the likelihood of VUR. VUR is classified by grade ( see Table: Grades of Vesicoureteral Reflux* Grades of Vesicoureteral Reflux* ).

Recurrent UTI is clearly associated with VUR, especially VUR of higher grades. This association is likely due to two factors—that VUR predisposes to infection and recurrent infections can worsen VUR. The relative contribution of each factor in children with recurrent UTI is unclear. Children with more severe reflux may have higher risk of developing hypertension and renal failure (caused by repeated infection and chronic pyelonephritis), but the evidence is not definitive (see treatment of VUR Vesicoureteral reflux Urinary tract infection (UTI) is defined by ≥ 5 × 10⁴ colonies/mL in a catheterized urine specimen or, in older children, by repeated voided specimens with ≥ 10⁵ colonies/mL... read more ).

Many organisms cause urinary tract infection in anatomically abnormal urinary tracts.

In relatively normal urinary tracts, the most common pathogens are

E. coli causes > 80 to 90% of UTIs in all pediatric age groups.

The remaining causes are other gram-negative enterobacteria, especially Klebsiella Klebsiella, Enterobacter, and Serratia Infections The gram-negative bacteria Klebsiella, Enterobacter, and Serratia are closely related normal intestinal flora that rarely cause disease in normal hosts. Diagnosis is by... read more , Proteus mirabilis Proteeae Infections The Proteeae are normal fecal flora that often cause infection in patients whose normal flora have been disturbed by antibiotic therapy. The Proteeae constitute at least 3 genera of gram-negative... read more , and Pseudomonas aeruginosa Pseudomonas and Related Infections Pseudomonas aeruginosa and other members of this group of gram-negative bacilli are opportunistic pathogens that frequently cause hospital-acquired infections, particularly in ventilator... read more . Enterococci Enterococcal Infections Enterococci are gram-positive, facultative anaerobic organisms. Enterococcus faecalis and E. faecium cause a variety of infections, including endocarditis, urinary tract infections... read more and coagulase-negative staphylococci Staphylococcal Infections Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more (eg, Staphylococcus saprophyticus) are the most frequently implicated gram-positive organisms.

Fungi and mycobacteria are rare causes, occurring in immunocompromised hosts.

Adenoviruses rarely cause UTIs, and when they do, the disorder is predominantly hemorrhagic cystitis among immunocompromised hosts.

A reliable diagnosis of urinary tract infection requires the presence of pyuria on urinalysis and positive bacterial culture in properly collected urine, before an antimicrobial is given. A diagnosis of probable UTI may be made by the presence of pyuria on urinalysis, while culture results are pending. Most clinicians obtain urine by transurethral catheterization in infants and young children, reserving suprapubic aspiration of the bladder for boys with moderate to severe phimosis. Both procedures require technical expertise, but catheterization is less invasive, slightly safer, and has sensitivity of 95% and specificity of 99% compared with suprapubic aspiration. Bagged specimens are unreliable and should not be used for diagnosis.

Urine culture results are interpreted based on colony counts. If urine is obtained by catheterization or suprapubic aspiration, ≥ 5 × 10⁴ colonies/mL commonly defines UTI. Clean-catch, midstream-voided specimens are significant when colony counts of a single pathogen (ie, not the total count of mixed flora) are ≥ 10⁵ colonies/mL. However, at times symptomatic children may have UTI despite lower colony counts on urine cultures. Urine should be examined by urinalysis and cultured as soon as possible or stored at 4° C if a delay of > 10 minutes is expected. Occasionally, UTI may be present despite colony counts lower than the described guidelines, possibly because of prior antibiotic therapy, very dilute urine (specific gravity < 1.003), or obstruction to the flow of grossly infected urine. Sterile cultures generally rule out UTI unless the child is receiving antibiotics or the urine is contaminated with antibacterial skin-cleaning agents.

Microscopic examination of urine is very useful but not definitive. Pyuria (> 5 white blood cells (WBCs)/high-power field in spun urine sediment) is about 96% sensitive for UTI and 91% specific. Raising the threshold of pyuria to > 10 WBCs/high-power field in spun urine sediment decreases the sensitivity to 81% but is more specific (97%). A WBC count (using a hemocytometer) > 10/mcL (0.01 × 10⁹/L) in unspun urine has greater sensitivity (90%) but is not used by many laboratories. Presence of bacteria on urinalysis of spun or unspun fresh urine is about 80 to 90% sensitive but only 66% specific; Gram stain of the urine to detect the presence of bacteria is about 80% sensitive and 80% specific.

Dipstick tests on urine to detect gram-negative bacteria (nitrite test) or WBC (leukocyte esterase test) are typically done together; if both are positive, the diagnostic sensitivity for UTI is about 93 to 97% and the specificity is about 72 to 93%. Sensitivity is lower for each individual test, especially for the nitrite test (about 50% sensitivity), because it may take several hours for bacterial metabolism to produce nitrites, and frequent voiding by children may preclude nitrite detection. The specificity of the nitrite test is quite high (about 98%); a positive result on a freshly voided specimen is highly predictive of UTI. Sensitivity of the leukocyte esterase test is 83 to 96% and specificity is 78 to 90%.

In a recent multicenter analysis of infants with fever, the aggregate urinalysis findings of pyuria, positive leukocyte esterase, or presence of nitrites was 90 to 95% sensitive and 91% specific for UTI; in the study population, this yielded a positive predictive value of 40% and a negative predictive value of 100% (1 Urine tests reference Urinary tract infection (UTI) is defined by ≥ 5 × 10⁴ colonies/mL in a catheterized urine specimen or, in older children, by repeated voided specimens with ≥ 10⁵ colonies/mL... read more ).

Differentiating an upper UTI from a lower UTI can be difficult. High fever, costovertebral angle tenderness, and gross pyuria with casts indicate pyelonephritis; an elevated C-reactive protein level also tends to be associated with pyelonephritis. However, many children without these symptoms and signs have an upper UTI. Tests to distinguish upper infection from lower infection are not indicated in most clinical settings because treatment is not altered.

A complete blood count and tests for inflammation (eg, erythrocyte sedimentation rate, C-reactive protein) may help diagnose infection in children with borderline urine findings. Some authorities measure serum blood urea nitrogen and creatinine during a first UTI. Blood cultures are appropriate for infants with UTIs and for children > 1 to 2 years who appear toxic.

Many major renal or urologic anomalies now are diagnosed in utero by routine prenatal ultrasonography, but a normal result does not completely exclude the possibility of anatomic anomalies. Thus, renal and bladder ultrasound imaging is typically done in children < 3 years of age after their first febrile urinary tract infection. Some clinicians do imaging on children up to 7 years of age or older.

Renal and bladder ultrasonography helps exclude obstruction and hydronephrosis in children with febrile UTIs and is typically done within a week of diagnosing UTI in infants. Ultrasonography is done within 48 hours if infants do not respond quickly to antimicrobials or if their illness is unusually severe. Beyond infancy, ultrasonography may be done in the few weeks after the UTI diagnosis.

Voiding cystourethrography (VCUG) and radionuclide cystography (RNC) are better than ultrasonography for detecting vesicoureteral reflux and anatomic abnormalities and previously were recommended for most children after a first urinary tract infection. However, VCUG and RNC both involve use of radiation and are more uncomfortable than ultrasonography. Also, the role VUR plays in the development of chronic renal disease is undergoing reevaluation, making the immediate diagnosis of VUR less urgent. Thus, VCUG is no longer routinely recommended after the first UTI in children, especially if ultrasonography is normal and if children respond quickly to antibiotic therapy. VCUG is reserved for children with the following:

If VCUG is to be done, it is done at the earliest convenient time after clinical response, typically toward the end of therapy, when bladder reactivity has resolved and urine sterility has been regained. If imaging is not scheduled until after therapy is due to be completed, children should continue antibiotics at prophylactic doses until VUR is excluded.

Radionuclide scanning is now used mainly to detect evidence of renal scarring. It is done using technetium-99m-labeled dimercaptosuccinic acid (DMSA), which images the renal parenchyma. DMSA scanning is not a routine test, but it may be done if children have risk factors such as abnormal ultrasound results, high fever, and organisms other than E. coli.

It has long been thought that antibiotic prophylaxis reduces UTI recurrences and prevents kidney damage and should be started after a first or second febrile UTI in children with VUR. However, this conclusion was not based on long-term, placebo-controlled trials (important because it has been observed that much VUR abates with time as children mature). A large, controlled trial, the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial (2 Treatment references Urinary tract infection (UTI) is defined by ≥ 5 × 10⁴ colonies/mL in a catheterized urine specimen or, in older children, by repeated voided specimens with ≥ 10⁵ colonies/mL... read more ), did show that antibiotic prophylaxis using TMP/SMX reduced UTI recurrences by 50% (from about 25% to 13%) compared to placebo but did not show a difference in the rate of renal scarring at 2 years (8% in each group). Also, the children in the trial who did develop UTI while taking prophylactic antibiotics were 3 times as likely to be infected with resistant organisms. However, because the 2-year follow-up period is likely too short to draw firm conclusions regarding prevention of renal scarring, additional study may show that antibiotic prophylaxis does provide some renal protection but at the risk of more antibiotic-resistant infections. Thus, the optimal strategy remains somewhat uncertain.

Nonetheless, for children with grade IV or V VUR, open repair or endoscopic injection of polymeric bulking agents is usually recommended, often along with antibiotic prophylaxis until repair is completed. For children with lesser grades of VUR, further research is required. Because renal complications are probably unlikely after only one or two UTIs, pending further research one acceptable strategy may be to closely monitor children for UTIs, treat them as they occur, and then reconsider antimicrobial prophylaxis in those children with recurrent infections (especially for those with recurrent febrile UTIs, more severe VUR, or bowel or bladder dysfunction).

Drugs commonly used for prophylaxis, if prophylaxis is desired, include nitrofurantoin 2 mg/kg orally once a day or TMP/SMX 3 mg/kg orally (of TMP component) once a day (3 Treatment references Urinary tract infection (UTI) is defined by ≥ 5 × 10⁴ colonies/mL in a catheterized urine specimen or, in older children, by repeated voided specimens with ≥ 10⁵ colonies/mL... read more ), usually given at bedtime.