Urinary Tract Infection (UTI) in Children
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. In younger children, UTIs are frequently associated with anatomic abnormalities. UTI may cause fever, failure to thrive, flank pain, and signs of sepsis, especially in young children. Treatment is with antibiotics. Follow-up imaging studies of the urinary tract are done.
UTI may involve the kidneys, bladder, or both. Sexually transmitted infections of the urethra (eg, gonococcal or chlamydial urethritis), although involving the urinary tract, are not typically termed UTI.
Mechanisms that maintain the normal sterility of the urinary tract include urine acidity and free flow, a normal emptying mechanism, intact ureterovesical and urethral sphincters, and immunologic and mucosal barriers. Abnormality of any of these mechanisms predisposes to UTI.
By age 6 yr, 3 to 7% of girls and 1 to 2% of boys have had a urinary tract infection. The peak age of UTI is bimodal, with one peak in infancy and the other peak between ages 2 to 4 yr (at the time of toilet training for many children). The female:male ratio ranges from 1:1 to 1:4 in the first 2 mo of life (estimates vary, likely because of different proportions of uncircumcised males in study groups and the exclusion of infants with urologic anomalies now more commonly diagnosed in utero by prenatal ultrasonography). The female:male ratio quickly rises with age, being about 2:1 between 2 mo to 1 yr, 4:1 during the 2nd yr, and > 5:1 after 4 yr. In girls, infections usually are ascending and less often cause bacteremia. The marked female preponderance beyond infancy is attributed both to the shorter female urethra and male circumcision.
Predisposing factors in younger children include
Other predisposing factors in younger children include constipation and Hirschsprung disease.
Predisposing factors in older children include
Urinary tract infections in children are a marker of possible urinary tract abnormalities (eg, obstruction, neurogenic bladder, ureteral duplication); these abnormalities are particularly likely to result in recurrent infection if vesicoureteral reflux (VUR) is present. About 20% to 30% of infants and children age 12 to 36 mo 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*).
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 Urinary Tract Infection (UTI) in Children : Vesicoureteral reflux).
Grades of Vesicoureteral Reflux*
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,Proteus mirabilis, and Pseudomonas aeruginosa. Enterococci (group D streptococci) and coagulase-negative staphylococci (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, also predominantly among immunocompromised hosts.
In neonates, symptoms and signs of urinary tract infection are nonspecific and include poor feeding, diarrhea, failure to thrive, vomiting, mild jaundice (which is usually direct bilirubin elevation), lethargy, fever, and hypothermia. Neonatal sepsis may develop.
Infants and children < 2 yr with UTI may also present with poorly localizing signs, such as fever, GI symptoms (eg, vomiting, diarrhea, abdominal pain), or foul-smelling urine. About 4 to 10% of febrile infants without localizing signs have UTI.
In children > 2 yr, the more classic picture of cystitis or pyelonephritis can occur. Symptoms of cystitis include dysuria, frequency, hematuria, urinary retention, suprapubic pain, urgency, pruritus, incontinence, foul-smelling urine, and enuresis. Symptoms of pyelonephritis include high fever, chills, and costovertebral pain and tenderness.
Physical findings suggesting associated urinary tract abnormalities include abdominal masses, enlarged kidneys, abnormality of the urethral orifice, and signs of lower spinal malformations. Diminished force of the urinary stream may be the only clue to obstruction or neurogenic bladder.
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 min 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 (> 3 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/μL 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%.
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 CBC and tests for inflammation (eg, ESR, C-reactive protein) may help diagnose infection in children with borderline urine findings. Some authorities measure serum BUN and creatinine during a first UTI. Blood cultures are appropriate for infants with UTIs and for children > 1 to 2 yr 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 yr of age after their first febrile urinary tract infection. Some clinicians do imaging on children up to 7 yr of age or older.
Renal and bladder ultrasonographyhelps 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 h 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 re-evaluation, 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.
Properly managed children rarely progress to renal failure unless they have uncorrectable urinary tract abnormalities. However, repeated infection, particularly in the presence of VUR, is thought (but not proved) to cause renal scarring, which may lead to hypertension and end-stage renal disease. In children with high-grade VUR, long-term scarring is detected at a 4- to 6-fold greater rate than in children with low-grade VUR and at an 8- to 10-fold greater rate than in children without VUR.
Treatment of urinary tract infection aims to eliminate the acute infection, prevent urosepsis, and preserve renal parenchymal function. Antibiotics are begun presumptively in all toxic-appearing children and in nontoxic children with a probable UTI (positive leukocyte esterase or nitrite test, or microscopy showing pyuria). Others can await the results of the urine culture, which are important for both confirming the diagnosis of UTI and yielding antimicrobial susceptibility results.
In infants 2 mo to 2 yr with toxicity, dehydration, or inability to retain oral intake, parenteral antibiotics are used, typically a 3rd-generation cephalosporin (eg, ceftriaxone 75 mg/kg IV/IM q 24 h, cefotaxime 50 mg/kg IV q 6 or 8 h). A 1st-generation cephalosporin (eg, cefazolin) may be used if typical local pathogens are known to be sensitive. Aminoglycosides (eg, gentamicin), although potentially nephrotoxic, may be useful in complex UTIs (eg, urinary tract abnormalities, presence of indwelling catheters, recurrent UTIs) to treat potentially resistant gram-negative bacilli such as Pseudomonas.
If blood cultures are negative and clinical response is good, an appropriate oral antibiotic (eg, cefixime, cephalexin, trimethoprim/sulfamethoxazole [TMP/SMX], amoxicillin/clavulanic acid, or, for selected children such as those > 1 yr with complicated UTI caused by multidrug-resistant E. coli,P. aeruginosa,or other gram-negative bacteria, a fluoroquinolone) selected on the basis of antimicrobial sensitivities can be used to complete a 7- to 14-day course. A poor clinical response suggests a resistant organism or an obstructive lesion and warrants urgent evaluation with ultrasonography and repeat urine culture.
In nontoxic, nondehydrated infants and children who are able to retain oral intake, oral antibiotics may be given initially. The drug of choice is TMP/SMX 5 to 6 mg/kg (of TMP component) bid. Alternatives include cephalosporins such as cefixime 8 mg/kg once/day, cephalexin 25 mg/kg qid, or amoxicillin/clavulanic acid 15 mg/kg/dose tid. Therapy is changed based on the results of cultures and antimicrobial sensitivities. Treatment is typically for 7 to 14 days. Urine culture is repeated 2 to 3 days after therapy starts only if efficacy is not clinically apparent.
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 recent large, controlled trial, the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial (1), 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 yr (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-yr 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 grade 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.
Drugs commonly used for prophylaxis, if prophylaxis is desired, include nitrofurantoin 2 mg/kg po once/day or TMP/SMX 3 mg/kg po (of TMP component) once/day, usually given at bedtime.
UTIs in children are frequently associated with urinary tract abnormalities such as obstruction, neurogenic bladder, and ureteral duplication.
The peak age of UTI is bimodal, one peak in infancy and the other peak usually at the time of toilet training for many children.
E. coli causes most UTIs in all pediatric age groups; the remaining causes are usually gram-negative enterobacteria (eg, Klebsiella,P. mirabilis,P. aeruginosa); frequently implicated gram-positive organisms are group D streptococci and coagulase-negative staphylococci (eg, S. saprophyticus).
Neonates and children < 2 yr with nonspecific symptoms and signs (eg, poor feeding, diarrhea, failure to thrive, vomiting) may have a UTI; children > 2 yr usually present with the symptoms and signs of cystitis or pyelonephritis.
Antibiotics are initiated presumptively in all toxic-appearing children and in nontoxic children with evidence of positive leukocyte esterase or nitrite test, or microscopy showing pyuria.
For children with high-grade vesicoureteral reflux (VUR), antibiotic prophylaxis is given until surgical correction is done; with lesser grades of VUR, the benefit of prophylactic antibiotics is unclear and close monitoring for recurrent UTI may be an acceptable management strategy for individual children.