|Year : 2012 | Volume
| Issue : 1 | Page : 1-3
Urinary tract infections in children: Consensus and controversies
Department of Nephrology, Osmania Medical College and General Hospital, Hyderabad, Andhra Pradesh, India
|Date of Web Publication||3-Dec-2012|
6-3-852/A, Ameerpet, Hyderabad, Andhra Pradesh - 500 016
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sahay M. Urinary tract infections in children: Consensus and controversies. J Acad Med Sci 2012;2:1-3
| Introduction|| |
Urinary tract infection (UTI) is one of the most common childhood infections. It causes discomfort for the child, worries the parents, and may lead to permanent kidney damage. The broad clinical categories of UTI are pyelonephritis (upper UTI) and cystitis (lower UTI). The growth of more than 1 lakh colony forming units per ml of a single species of organisms in mid stream urine generally defines UTI. Counts may vary with the method of urine collection. 
| Epidemiology|| |
The incidence of UTI varies with age. The occurrence of UTI is highest in boys and girls during the first year of life especially in neonates where the incidence is 7%. As many as 5% of children below age 2 years who present with fever have a UTI. Up to 7 % girls and 2% boys experience at least 1 episode of symptomatic culture positive UTI by 6 years of age.  In sexually active teenaged females, the incidence of UTIs approaches 10%. During the first year of life, the male to female ratio of UTI is 3-5:1. Beyond 1-2 years, there is female preponderance with male to female ratio of 1:10.  The prevalence of febrile UTI in white infants exceeds that in black infants.
| Clinical Features|| |
The febrile infant especially younger than 3 months or child with clinically significant bacteriuria and no other site of infection to explain the fever, even in the absence of systemic symptoms, may have UTI. Workup of fever in these infants should always include evaluation for UTI. Some infants may present with hypothermia, jaundice, respiratory distress, seizures, lethargy, etc. Older children may present with dysuria, hematuria, suprapubic, or loin pain. 
| Etiology|| |
Almost all UTIs are ascending in origin and begin in the bladder and then spread up the urinary tract to the kidneys (pyelonephritis) and to the bloodstream (bacteremia). Bacterial infections are the most common cause of UTI, with E. coli being the most frequent (75-90%) of UTIs. Other bacterial sources include the following: Klebsiella species, Proteus species, Enterococcus species, Staphylococcus saprophyticus - especially among female adolescents and sexually active females, Streptococcus group B - especially among neonates, Pseudomonas aeruginosa, Fungi (Candida species) - especially after instrumentation of the urinary tract and rarely adenovirus.
| Risk Factors for Infection|| |
Children younger than 5 years are predisposed to UTIs, because of periurethral colonization. These uropathogens are rare in children older than 5 years. Normal voiding results in complete washout of contaminating bacteria, pathogenic colonization of the urinary bladder is unlikely unless bladder defense mechanisms are impaired. Risk factors for UTI include anatomic anomaly (posterior urethral valves), voiding dysfunction (uninhibited detrusor contractions or neurogenic bladder), or constipation. Children who receive broad-spectrum antibiotics (e.g., amoxicillin, cephalexin) which alter gastrointestinal (GI) and periurethral flora are at an increased risk for UTI, because these drugs disturb the urinary tract's natural defense against colonization by pathogenic bacteria. The rate of UTIs in circumcised boys has been estimated at 0.2-0.4%, with the rate in uncircumcised boys being 5-20 times higher than in circumcised boys. In addition, some genes in humans may be associated with susceptibility to recurrent UTI. Also genetics may play a role in the progression of simple cystitis to pyelonephritis. Genetic testing may allow the identification of at-risk individuals and, therefore, prediction of genetic recurrences in their offspring. Non-secretors of P blood group antigen are also predisposed to UTI.
| Bacterial Virulence Factors|| |
Some strains of E. coli are uropathogenic by virtue of their pili and fimbriae. Also some serotypes are more uropathogenic than others. E. coli which are protoplast forms are resistant to drug treatment.
| Diagnosis|| |
The diagnosis of UTI is based on the quantitative culture of a properly collected urine specimen. A midstream, clean-catch specimen may be obtained from children who have urinary control. ,,, In the infant or child unable to void, the specimen for culture should be obtained by means of suprapubic aspiration or urethral catheterization. ,,, A culture of a urinary specimen from a sterile bag or pad is not sufficiently diagnostic.
Clear urine (defined as the ability to read text through the urine in a test tube as easily as through water) had 96% to 100% negative predictive value, but this is unreliable in dilute urine. Microscopic examination of spun urine can demonstrate the presence of white blood cells (WBCs), red blood cells (RBCs), bacteria, and casts. The presence of five or more WBCs/high-power field suggests an infection. Gram stain of unspun urine may reveal organisms. Approximately 10-20% of pediatric patients with UTI have normal urinalysis results.
It can test for WBC in urine (leucocyte esterase) and the presence of bacteria (Greiss Nitrite test). The dipstick test is non-invasive, cheap, and can be done in the clinic in few minutes. Urine dipstick analysis can rule out UTI if the result is negative in nondilute urine. Urine dipstick is acceptable in children with a low likelihood of UTI.  Urine dipstick can also be the initial test in older children and may obviate the need for culture. 
Urinalysis is not a substitute for urine culture as false-positive results are common. Children with a high likelihood of UTI, those with cloudy urine, those with dipstick test positive for leukocyte esterase or nitrite activity, or children with recurrent symptoms should have a urine culture.
Hematologic studies, Renal function, and blood cultures should be done in patients who are clinically ill or toxic.
| Imaging|| |
Ultrasonography of the urinary tract has replaced the use of intravenous pyelography (IVP). Ultrasonography is a safe, noninvasive study that is easy to perform. It is useful in excluding obstructive uropathy and in identifying children with a solitary or ectopic kidney. American Academy of Pediatrics (AAP) Clinical Practice Guidelines initially recommended routine ultrasonography after a first febrile UTI in children.  Similar guidelines were given by Indian academy of pediatrics.  However, current recommendations by AAP state that following pediatric patients should also undergo ultrasonography of the urinary tract after a febrile UTI - children aged 2-24 months, delayed or unsatisfactory response to treatment of the first febrile UTI, an abdominal mass or abnormal voiding (dribbling of urine), a first febrile UTI caused by an organism other than E. coli, children with recurrence of a febrile UTI, and child with a first febrile UTI in whom good follow-up cannot be ensured.  The clinician's judgment should guide the decision regarding imaging studies, as opposed to a rigid rule.
In this procedure, the dye is instilled into the bladder per urethra or suprapubic injection and the child is made to void and bladder contour and any back flow of urine (reflux) from bladder to ureters is looked for. VCG also demonstrates any post urethral valves which may block the urethra. Initially, the AAP recommended that all infants and young children (aged 2 months to 2 years) with a first UTI undergo Voiding Cystourethrography (VCUG).  The same was also recommended by Indian guidelines.  This was based on the assumption that most upper UTIs occur because of urinary bladder infection and that vesicoureteral reflux (VUR) transfers bacteria in the bladder to the kidney. However, current data show that upper tract infection occurs equally in children with or without VUR. Also initially, it was thought that antibacterial prophylaxis prevents a recurrence of UTI, However, a review of literature published since 2005 suggested that the risk of developing long-term complications after a UTI is low and the role of antibiotic prophylaxis is doubtful. Thus, VCUG is not recommended routinely after the first UTI by the latest AAP guidelines  and British NICE guidelines.  The following pediatric patients need imaging studies after a first UTI: infants and children with a first febrile UTI who do not have assured follow-up, who do not respond promptly to treatment (afebrile within 72 h), who have an abnormal voiding pattern ( dribbling), those with an abdominal mass, infants and children with cystitis, with abnormal voiding pattern, if renal and bladder ultrasonography reveal hydronephrosis, scarring, or other findings that suggest either high-grade VUR or obstructive uropathy, recurrence of a febrile UTI.  If a VCUG is to be obtained, it should not be obtained until the infection is cleared, usually 4-6 weeks interval is recommended or earlier if infection clears early and the voiding pattern returns to its pre-UTI state. The child should receive antibacterial therapy at least until the cystogram is obtained. 
DMSA (Renal scan)
In this procedure, the dye is injected intravenously and the renal images are obtained. The renal scars can be seen as photopenic areas. Indian guidelines recommend both VCUG and DMSA in children 2 months to 2 years of age and DMSA alone in children between 2 and 5 years of age.  If DMSA is abnormal, VCUG should be done.  However, DMSA is not recommended in the routine evaluation of children with first UTI as per the AAP  and NICE guidelines,  the latter recommends DMSA only in recurrent UTI.
| Treatment|| |
Most children with uncomplicated UTI respond readily to outpatient antibiotic treatments and fluids. Outpatient treatment with oral antibiotics should be given if the child is not acutely ill or toxic, immunocompromised, if the child does not have persistent vomiting or dehydration. The children with a febrile UTI should receive oral treatment with a second- or third-generation cephalosporin (cefpodoxime, cefixime,cefdinir), amoxicillin clavulanate, or sulfamethoxazole-trimethoprim (SMZ-TMP). If child is on catheter, enterococcus may be suspected and ampicillin should be added. Oral cephalexin, ampicillin, or amoxicillin may be used as monotherapy if no resistance is suspected.  The AAP Committee on Infectious Diseases recommends that the use of ciprofloxacin for UTI in children be limited to UTI caused by Pseudomonas aeruginosa or other multidrug-resistant, gram-negative bacteria.  Oral agents that are excreted in the urine but do not achieve therapeutic serum (e.g., nalidixic acid, nitrofurantoin) should not be used to treat UTI in febrile infants and young children. Duration of therapy is 10 days for febrile children and 3-5 days for immunocompetent patients though shorter courses are being studied. Previous antibiotic exposure (i.e., for otitis media) is associated with drug-resistant UTIs and should be considered when choosing empiric therapy. Toxic children and neonates must be aggressively treated with intravenous fluids and parenteral antibiotics. Ceftioxone, cefotaxime, cefipime, ceftazidime, or piperacillin may be used.  Gentamicin is an alternative for those who are allergic to cephalosporins. Ampicillin should be added if gram-positive cocci are present in the urinary sediment or if no organisms are observed. Results of urine culture and sensitivity studies are usually available within 48 h. If the pathogen is sensitive to the antibiotic used and if the child is improving, continue parenteral treatment until the child is afebrile for 24-36 h. An oral antibiotic that is effective against the infecting organism may then be substituted for parenteral therapy. The hospitalized child can be discharged after 48-72 h. There is no need to repeat the urine culture in children with UTI who are treated with an antibiotic to which the uropathogen is susceptible. Imaging is done if fever does not subside in 48 h.  Children with cystitis usually do not require special medical care other than appropriate antibiotic therapy for 3-7 days and symptomatic treatment if voiding symptoms are marked. Use of antibiotics to treat asymptomatic bacteriuria or antibiotic prophylaxis is not indicated.  Low-grade VUR usually resolves without permanent damage, but high-grade VUR may require surgical correction. 
There is a considerable controversy regarding antibiotic prophylaxis. Antibiotic prophylaxis is recommended in Indian guidelines.  The revised AAP practice guideline and NICE guidelines do not recommend prophylactic antimicrobials following the first febrile UTI in children 2 to 24 months, , the latter recommends prophylaxis only for recurrent UTI. Conclusive evidence on the benefits of antimicrobial prophylaxis is expected from the randomized intervention for vesicoureteral reflux (RIVUR) study. 
Circumcision is not recommended routinely but may be considered for infants with recurrent UTI. Attention to under-garments and perineal hygiene should be explained to the parents. Plenty of fluid intake and frequent voiding ensures flushing out of the uropathogens. Constipation predisposes to recurrent UTI and improvement in bowel habits reduces the incidence of UTI. In children with VUR regular and voluntary low pressure voiding with complete bladder emptying is encouraged. Double voiding is recommended in order to empty the bladder. Daily consumption of concentrated cranberry juice can significantly prevent the recurrence of UTI in older children. 
| Prognosis|| |
Mortality related to UTI is exceedingly rare in otherwise healthy children in developed countries. Morbidity associated with pyelonephritis may be associated with clinical sepsis as has been highlighted by Youssef et al in this issue.  Long-term complications of pyelonephritis are hypertension, impaired kidney function, end-stage renal disease, and complications of pregnancy (e.g., UTI, pregnancy-related hypertension, low-birth-weight neonates). 
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