A state-of-the art review of current literature on UTI in children, with a particular focus on its diagnosis and management by general pediatricians.

Urinary tract infection (UTI) is common in children, and girls are at a significantly higher risk, as compared to boys, except in early infancy. Most cases are caused by Escherichia coli. Collection of an uncontaminated urine specimen is essential for accurate diagnosis. Oral antibiotic therapy for 7 to 10 days is adequate for uncomplicated cases that respond well to the treatment. A renal ultrasound examination is advised in all young children with first febrile UTI and in older children with recurrent UTI. Most children with first febrile UTI do not need a voiding cystourethrogram; it may be considered after the first UTI in children with abnormal renal and bladder ultrasound examination or a UTI caused by atypical pathogen, complex clinical course, or known renal scarring. Long-term antibiotic prophylaxis is used selectively in high-risk patients. Few patients diagnosed with vesicoureteral reflux after a UTI need surgical correction. The most consequential long-term complication of acute pyelonephritis is renal scarring, which may increase the risk of hypertension or chronic kidney disease later in life. Treatment of acute pyelonephritis with an appropriate antibiotic within 48 hours of fever onset and prevention of recurrent UTI lowers the risk of renal scarring. Pathogens causing UTI are increasingly becoming resistant to commonly used antibiotics, and their indiscriminate use in doubtful cases of UTI must be discouraged.

Urinary tract infection (UTI) is one of the most common bacterial infections in childhood. In the first year of life, it is more common in boys (3.7%), as compared to girls, (2%) and after infancy, it is significantly more prevalent in girls. During prepubertal age, the incidence in girls is 3%, as compared to 1% in boys.13  The risk of UTI recurrence in the first 6 to 12 months after the initial UTI is ∼12% to 30%.4,5  Besides sex, other significant risk factors for UTI are bladder-bowel dysfunction (BBD); congenital anomalies of kidneys and the urinary tract (CAKUT), including vesicoureteral reflux (VUR); and the circumcision status in young boys.4,68  Approximately 85% to 90% of UTIs are caused by Escherichia coli. Other common organisms include Klebsiella, Proteus, Enterococcus, and Enterobacter species.911  Organisms such as Pseudomonas, group B Streptococcus, and Staphylococcus aureus are usually associated with CAKUT, genitourinary surgery, a foreign body (eg, catheter), or recent antibiotic treatment, whereas infection with urea-splitting organisms (eg, Proteus) is associated with stone formation.8,12  Prompt diagnosis and treatment are important for the prevention of acute complications as well as renal scarring. In the last 2 decades, a significant amount of research has been done on UTI in children, particularly on renal imaging and long-term antibiotic prophylaxis after UTI. The objective of this review is to summarize the current literature on UTI in children, with an emphasis on its clinical management.

The definitions that are often used in association with UTI relate to its clinical presentation, site and severity of infection, frequency of UTI, and the occurrence of renal scarring. Frequently used definitions are elaborated in Table 1.

TABLE 1

Frequently Used Terms for UTI

CategoryTermDefinition
Signs and symptoms Febrile UTI UTI associated with temperature ≥38°C (100.4°F) 
 Symptomatic UTI UTI associated with fever and/or urinary symptoms 
 ABU Significant bacteriuria in a child with no symptoms of UTI 
 Sterile pyuria Increased white cells in urine in the absence of bacteria on urine culture 
 BBD Spectrum of signs and symptoms, including incontinence, constipation and/or encopresis associated with functional and behavioral abnormalities of the bowel, lower urinary tract, and pelvic floor 
Site of infection Upper-tract UTI UTI involving kidneys and ureters 
 Lower-tract UTI UTI involving bladder and urethra but not upper tract 
 Pyelonephritis Kidney infection (febrile UTI may or may not be due to pyelonephritis) 
 Cystitis Bladder infection 
Severity of infection Complicated UTI UTI in newborns; abdominal and/or bladder mass; kidney and urinary tract anomalies; urosepsis; organism other than E coli; atypical clinical course, including absence of clinical response to antibiotic within 72 h; and renal abscess 
 Complicated cystitis Children with comorbid medical conditions, underlying bladder pathology, indwelling bladder catheter, and atypical clinical course 
Renal status Reflux nephropathy Renal cortical abnormalities associated with VUR (may be congenital dysplasia or acquired scarring) 
 Renal scarring Acquired renal damage due to APN 
 Renal dysplasia Congenital renal cortical abnormalities 
CategoryTermDefinition
Signs and symptoms Febrile UTI UTI associated with temperature ≥38°C (100.4°F) 
 Symptomatic UTI UTI associated with fever and/or urinary symptoms 
 ABU Significant bacteriuria in a child with no symptoms of UTI 
 Sterile pyuria Increased white cells in urine in the absence of bacteria on urine culture 
 BBD Spectrum of signs and symptoms, including incontinence, constipation and/or encopresis associated with functional and behavioral abnormalities of the bowel, lower urinary tract, and pelvic floor 
Site of infection Upper-tract UTI UTI involving kidneys and ureters 
 Lower-tract UTI UTI involving bladder and urethra but not upper tract 
 Pyelonephritis Kidney infection (febrile UTI may or may not be due to pyelonephritis) 
 Cystitis Bladder infection 
Severity of infection Complicated UTI UTI in newborns; abdominal and/or bladder mass; kidney and urinary tract anomalies; urosepsis; organism other than E coli; atypical clinical course, including absence of clinical response to antibiotic within 72 h; and renal abscess 
 Complicated cystitis Children with comorbid medical conditions, underlying bladder pathology, indwelling bladder catheter, and atypical clinical course 
Renal status Reflux nephropathy Renal cortical abnormalities associated with VUR (may be congenital dysplasia or acquired scarring) 
 Renal scarring Acquired renal damage due to APN 
 Renal dysplasia Congenital renal cortical abnormalities 

The pathogenesis of acute pyelonephritis (APN) and renal scarring is complex and not fully understood. Most UTIs are ascending infections that start with periurethral colonization; hematogenous spread occurs primarily in debilitated, obstructed, or immunocompromised patients, and these are mostly fungal and staphylococcal infections.13  The virulence of uropathogenic E coli is largely influenced by the presence of P fimbriae, also known as pyelonephritis-associated pili, and lipopolysaccharide. The binding of the P fimbriae to epithelial cells is mediated by the tip adhesin PapG. Bacterial lipopolysaccharide is important for the initiation of tissue inflammation. It is bound in the kidney by toll-like receptor 4, which is a transmembrane protein and a member of the toll-like receptor family. These receptors are present on the epithelial cells and parts of the renal tubule. Their activation leads to a release of proinflammatory cytokines and chemokines and the recruitment of neutrophils.14,15  Lipopolysaccharide also activates the recruited macrophages. The presence of macrophages, dendritic cells, and T cells in renal interstitium induces inflammation via modulation of immune response through recruitment and activation of neutrophils16  and the generation of reactive oxygen species, resulting in killing the pathogen.

The fibrosis and scarring that follows is initiated by macrophages and conducted by neutrophils.17  Monocyte chemoattractant protein-1, which is secreted by kidney epithelial cells, recruits monocytes at the site of infection. Monocytes differentiate into 2 groups of macrophages: proinflammatory monocytes that kill the pathogen by secreting inflammatory cytokines (such as interleukins and tumor necrosis factor α) as well as cytotoxic reagents (such as nitric oxide synthase and reactive oxygen species) and anti-inflammatory monocytes that terminate the inflammatory response. Depending on the severity of kidney damage, the latter also induces kidney fibrosis through transforming growth factor β. The proinflammatory response, which is necessary for killing the pathogen, also damages the surrounding tissue, causing tissue ischemia, tubular cell death, and reperfusion injury. The fibrosis and scarring that follows is initiated by macrophages.16,1820 

The important risk factors for UTI in children are female sex (or uncircumcised infant boy), younger age, high-grade VUR, CAKUT, BBD, and instrumentation of the urinary tract (particularly indwelling bladder catheterization).2,4,2123  Other risk factors for UTI in older children and adolescents include the presence of kidney stones, sexual activity, and diabetes. Genetic factors also influence the occurrence of UTI.24  Administration of an antibiotic may increase the risk of UTI by changing periurethral microflora.25  A calculator was recently developed to help clinicians estimate the probability of UTI in febrile infants at the bedside (https://uticalc.pitt.edu).26  It is based on risk factors that include age <12 months, female sex (or uncircumcised boy), maximum temperature >39°C, and the absence of another source for fever. The calculator was validated in a cohort of >2000 children and was found to reduce unnecessary testing, decrease missed UTIs, and reduce treatment delays. Bubble baths may infrequently cause irritation and discomfort of the genital mucosa and periurethral tissue in children,27  which may be wrongly interpreted as a UTI: there is little evidence that the bubble baths actually cause UTI.28 

A number of risk factors are associated with acquired renal scarring due to APN. These include a high grade of VUR (grades >2 and particularly grades 4 and 5),7,29  duration of fever of >72 hours before antibiotic initiation,3032  recurrent UTI,29,3335  and organisms other than E coli.3638  Previously, a young age was considered to be a risk factor, but recent studies have revealed that older children may be at higher risk of renal scarring29,36,39 ; the discrepancy may be related to the inadvertent inclusion of patients with preexisting congenital scarring (renal dysplasia) in the earlier studies because differentiation between congenital and acquired scarring after APN is challenging, particularly when baseline (ie, pre-UTI) studies are not available. In comparison with the other pathogens, infection with P fimbriae E coli increases the probability of ascending infection but does not appear to be associated with increased dimercaptosuccinic acid (DMSA) renal scan abnormalities.40  It has long been speculated that there is a genetic predisposition in some children to develop renal scarring after APN. Polymorphisms of the HSPA1B gene of HSP72 protein were found to be associated with renal scarring,41  whereas variants of the toll-like receptor 4 gene were associated with renal scarring in another study.42  In other studies, researchers have indicated potential roles for polymorphisms of the angiotensin-converting enzyme and transforming growth factor β1 genes.43  In studies of plasminogen activator inhibitor 1, researchers found that it was not associated with risk of renal scarring among infants after first febrile UTI.44 

A targeted history and physical examination and positive urinary findings are essential for an accurate diagnosis of UTI.

  • History and physical examination: In older, verbal children, important findings include dysuria, urgency and/or frequency, abdominal or flank pain, and new-onset incontinence.45  In contrast, signs and symptoms of UTI in infancy are nonspecific, and fever may be the only symptom, although neonates may present with hypothermia. History of constipation, UTI in siblings or parents, and recent infections or antibiotic treatment should be ascertained. Relevant signs on abdominal examination include distention, presence of a mass or palpable stool, flank or suprapubic tenderness, and/or a palpable bladder, particularly after voiding.

  • Urine specimen: In non–toilet-trained children, urine collection method has a profound significance for diagnosis of UTI. Urine specimen in such children should be collected preferably by ureteral catheterization or suprapubic bladder aspiration, particularly if a specimen collected by perineal bag is dipstick-positive. In a recent video published in the New England Journal of Medicine, researchers reviewed the methods of suprapubic aspiration.46  Another reasonable alternative is the Quick-Wee method of urine collection.47  In this method, the suprapubic area is stimulated by using a gauze soaked in cold fluid, and the voided midstream urine is caught in a sterile cup.48  Regardless of the technique, contamination of voided specimens from infants is a significant concern, particularly for girls and uncircumcised, young boys. In older, toilet-trained children, a urine specimen can be obtained by catching the midstream urine in a sterile cup after cleaning of skin around the genital area; girls may benefit from facing backward on the toilet, which splays the legs and labia and may reduce contamination from skin and vaginal surfaces. In uncircumcised boys, gentle retraction of the prepuce (if possible) is important to obtain an uncontaminated specimen, and urine from boys with significant phimosis is likely to be contaminated.

  • Urinalysis: Antibiotic treatment of UTI is often started empirically because urine culture results take 1 to 2 days. The leukocyte esterase test on urine dipstick is the most widely available screening test. The results are usually reported semiquantitatively (negative, trace, 1+, 2+, and 3+). The accuracy of currently available screenings tests for UTI is summarized in Table 2.49  The table also demonstrates that the currently available bedside tests have a high rate of false-positive and negative results with treatment implications. A microscopic urinalysis has only marginally better accuracy than the dipstick. Until better and more accurate biomarkers for UTI become available, the limitation of bedside UTI screening should be kept in mind and used only in conjunction with clinical assessment. Blood and/or protein on urine dipstick examination are poor indicators of UTI.

  • Urine culture: The acceptable colony count threshold for a urine culture positive for UTI depends on its collection method. It is 50 000 colony-forming units (CFUs)/mL for samples obtained by catheterization, 100 000 for samples obtained by clean catch, and 1000 CFU/mL on samples obtained by suprapubic aspiration. The 2011 American Academy of Pediatrics (AAP) guideline defines UTI by the presence of at least 50 000 CFU/mL of a uropathogen in a specimen obtained by bladder catheterization in a child with either a positive result on a leukocyte esterase test or with white blood cells in the urine on microscopy (ie, pyuria).34  However, requiring pyuria for diagnosis has recently been questioned because of the relatively low accuracy of pyuria or the leukocyte esterase test, reportedly low prevalence of asymptomatic bacteria,50  and the relatively low rate of contamination in samples obtained by using a urinary catheter. Another recent finding that further complicates matters is that UTI with different organisms may be associated with different degrees of pyuria; Enterococcus species, Klebsiella species, and Pseudomonas species in particular seem to have a proclivity to cause infection in the absence of pyuria.51  Also controversial is the use of a single colony count threshold for all children.52  Several studies have revealed that some children with lower colony counts have true UTIs and even pyelonephritis.53  As such, the definition of UTI is likely to continue to evolve as new data emerge. In the meantime, we recommend using the AAP guideline, in combination with clinical judgement, to determine the likely diagnosis.

  • Blood tests: Blood tests, such as complete blood counts, serum chemistry, and renal function tests, are not routinely needed for patients with UTI and should be done only if clinically indicated.

TABLE 2

Accuracy of Widely Available Bedside Tests for UTI in a Hypothetical Cohort of 1000 Children Tested for UTI

Sensitivity, %Specificity, %No. Unnecessary Antibiotic PrescriptionsaNo. With Delayed or Missed Diagnosisa
Leukocyte esterase 79 87 120 16 
Nitrite 49 98 18 38 
Leukocyte esterase or nitrite 88 79 194 
Sensitivity, %Specificity, %No. Unnecessary Antibiotic PrescriptionsaNo. With Delayed or Missed Diagnosisa
Leukocyte esterase 79 87 120 16 
Nitrite 49 98 18 38 
Leukocyte esterase or nitrite 88 79 194 
a

Assuming a prevalence of 7.5% (ie, 75 with UTI and 925 with no UTI).2,45 

  • Contaminated urine specimen: A diagnosis of UTI based on contaminated urine specimen may lead to unnecessary antibiotic treatment or delayed treatment in those with true UTIs. The contamination rates of bag urine specimens can be as high as 80%.34,54  The 2 most common sources of urine contamination are feces and skin that it may come in contact with while passing through the vagina or under the foreskin. Presence of ≥10 per high-power field squamous epithelial cells on urinalysis,55  insignificant bacterial colony count, or the presence of ≥2 pathogens on urine culture in midstream urine specimen is suggestive of contamination.55  Growth of nonuropathogens such as Lactobacillus, Corynebacterium, viridans streptococci, or coagulase-negative staphylococci such as Staphylococcus epidermidis are considered as contaminants in children.34 

  • Asymptomatic bacteriuria (ABU): Colonization of the bladder in the absence of an inflammatory reaction occurs at all ages, including infants and children. ABU is more common in girls and generally involves Gram-negative bacteria, such as E coli. Its reported incidence is ∼1% to 3%, and it usually resolves spontaneously in a few months to a couple of years, although in some girls, it may persist for much longer.5658  A recent meta-analysis of published literature reported a lower prevalence of ABU of <0.5%.50  Antibiotic treatment is not recommended for otherwise healthy individuals with ABU because its use promotes antimicrobial resistance and other adverse effects, including the possibility of an increased risk of symptomatic UTI.5962  ABU is frequently observed in children with neurogenic bladder, particularly if the patient is on clean intermittent catheterization or has a history of bladder augmentation.63 

  • Sterile pyuria: Sterile pyuria may occur in association with infections such as partially treated UTI, appendicitis, tuberculosis, or fungal, viral, or parasitic infections. It can also occur with immunologic conditions, such as acute glomerulonephritis, systemic lupus erythematosus, and Kawasaki disease, or with a foreign body, kidney stones, interstitial nephritis, analgesic nephropathy, and papillary necrosis.64,65 

Differentiation of APN from cystitis can be difficult particularly in preverbal children, and in the febrile infant, the distinction might be considered largely academic because treatment will be similar. Because most cases of APN are due to ascending infection, many patients have both upper- and lower-tract symptoms, further blurring the distinction between cystitis and APN. However, an effort should be made to localize the infection (because both the acute management and subsequent workup of cystitis and pyelonephritis may differ, particularly in older children) and to identify the causative organism (because patients with viral or chemical cystitis do not need conventional antibiotic therapy). Furthermore, unlike APN that needs second- or third-generation cephalosporin for at least 1 week, uncomplicated (nonfebrile) bacterial cystitis generally responds well to the short duration (3–5 days) of first-generation cephalosporin, trimethoprim-sulfamethoxazole, or nitrofurantoin.6669  The utility of currently available screening tests (C-reactive protein, procalcitonin, and erythrocyte sedimentation rate) is limited. The evidence suggests that an increased serum C-reactive protein or procalcitonin level is suggestive of APN.20  The erythrocyte sedimentation rate does not appear useful in diagnosing APN. Some other features that may be helpful in differentiating cystitis from APN are shown in Table 3.6669 

TABLE 3

Features That May Be Helpful in Differentiating Cystitis From APN

CharacteristicAPNUncomplicated Cystitis
Age distribution More common in younger children Typically in children aged >2 y 
Fever130  >38°C Afebrile or low-grade fever ≤38°C 
Recent viral illness131  NA Viral cystitis 
Systemic symptoms Common Uncommon 
Local symptoms Flank pain and/or tenderness Dysuria, urgency, frequency, urinary incontinence, suprapubic pain, and/or hematuria 
Causative agent Bacterial (E coli is the commonest) Bacterial (E coli is the commonest), viral, fungal, and chemical 
Urinary findings   
 Gross hematuria Uncommon May have fresh blood and clots131,132  
 Urine culture for bacteria Positive Negative results in viral, fungal, and chemical cystitis 
RBUS Normal or may reveal edema and hyperemia of kidney Normal or may reveal thickened urinary bladder wall, debris in the bladder 
Renal complication Renal scarring None 
CharacteristicAPNUncomplicated Cystitis
Age distribution More common in younger children Typically in children aged >2 y 
Fever130  >38°C Afebrile or low-grade fever ≤38°C 
Recent viral illness131  NA Viral cystitis 
Systemic symptoms Common Uncommon 
Local symptoms Flank pain and/or tenderness Dysuria, urgency, frequency, urinary incontinence, suprapubic pain, and/or hematuria 
Causative agent Bacterial (E coli is the commonest) Bacterial (E coli is the commonest), viral, fungal, and chemical 
Urinary findings   
 Gross hematuria Uncommon May have fresh blood and clots131,132  
 Urine culture for bacteria Positive Negative results in viral, fungal, and chemical cystitis 
RBUS Normal or may reveal edema and hyperemia of kidney Normal or may reveal thickened urinary bladder wall, debris in the bladder 
Renal complication Renal scarring None 

NA, not applicable.

Acute complications of UTI are similar to those associated with any febrile illness in a young child. These include dehydration, electrolyte abnormalities, and febrile seizures. Renal complications of APN are uncommon in otherwise healthy children but may include renal abscess or complete occlusion of a preexisting, partial ureteropelvic junction obstruction. Acute kidney injury may occur because of dehydration or an administration of a nonsteroidal anti-inflammatory drug, such as ibuprofen. Nonsteroidal anti-inflammatory drugs may also diminish renal function by causing papillary necrosis or interstitial nephritis. The latter can also be caused by the antibiotic that is being used for UTI treatment. Urosepsis may occur, particularly with Gram-negative infections.

The most consequential long-term complication of APN is renal scarring. The reported prevalence of renal scarring after febrile UTI is ∼15%39  and ranges from 3% after the first UTI to 29% after >3 febrile UTIs.36,70  In the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial, only ∼7% of children developed new scarring during the study period, and this was primarily among children with grade 4 VUR.29  In most children, renal scarring may not be clinically significant,7173  but it may cause hypertension and proteinuria and a progressive decline in renal function in those with bilateral significant scarring.74  Delayed initiation of antibiotic treatment is associated with increased risk of scarring, with the odds of new renal scarring 74% lower among children whose treatment started within 24 hours of onset of fever, compared with those whose treatment started after 72 hours of fever.32 

Renal imaging after UTI is driven primarily by a need to rule out an underlying renal or urinary tract anomaly or the assessment of renal injury.

The purpose of renal bladder ultrasound (RBUS) is to evaluate for urinary tract anomalies, including obstruction, renal structural anomalies, nephrolithiasis or calcification, or an abdominal mass. RBUS is a less sensitive imaging modality for the diagnosis of VUR,75  and normal RBUS does not rule out high-grade VUR. Particular findings on RBUS that may indicate a higher probability of VUR include ureteral dilation, renal parenchymal changes, and bladder abnormalities. RBUS cannot be used to accurately diagnose patients with APN or renal scarring.7678  The 2011 AAP guidelines recommend RBUS be performed in all infants (2–24 months) with febrile UTI.34  Older children with recurrent UTIs may also benefit from an RBUS. The RBUS can be deferred until after resolution of the UTI but should be considered during the acute episode if the illness seems unusually severe or if high fevers persist beyond 48 to 72 hours of treatment34 ; such atypical course suggests complications, such as renal abscess or occult obstruction, that are well-seen on RBUS. A deferred RBUS permits more accurate interpretation of the anatomy, without potential for false-positive findings associated with tissue edema or endotoxin-induced dilation.

In the last decade, the practice patterns have dramatically shifted, with far fewer patients undergoing voiding cystourethrogram (VCUG) after an initial UTI.79,80  This trend is consistent with many published guidelines, including those by the AAP.34,81,82  Part of the reason for this is that less than one-third of children with their first UTI have VUR, and of these, fewer than 10% have grade 4 to 5 VUR.7,83  A VCUG should be considered after first UTI in children with abnormal RBUS, atypical causative pathogen, complex clinical course, or known renal scarring.34,81,82,84  Patients with a family history of VUR or CAKUT can also be considered for VCUG after first febrile UTI. The interobserver variability in VUR grading must be kept in mind while making clinical decisions.85 

DMSA scan is the current gold standard for assessment of renal parenchymal injury in a child with a history of febrile UTI. It is more sensitive for renal scarring than RBUS, which misses a substantial proportion of such cases.40,86,87  However, most children with first febrile UTI do not need a DMSA renal scan.34  It may be considered in children with recurrent febrile UTIs or renal parenchymal abnormalities on RBUS. Demonstration of renal scarring increases the risk for further renal deterioration.88  Findings of renal scarring may influence surgical decision-making in patients with surgically correctable conditions (eg, VUR). Cortical defects on DMSA scan performed during or shortly after APN may be due to preexisting lesions (either acquired or congenital) or to the acute inflammatory reaction associated with APN. A delayed DMSA scan at 4 to 6 months allows the acute inflammatory reaction to subside, at which point any persistent cortical defects can be assumed to represent permanent renal scarring, although in the absence of baseline (pre-APN) scans, it may still be difficult to differentiate acquired from congenital lesions.89 

The choice of an antimicrobial for empirical therapy should be guided by the local, resistant patterns of uropathogens. However, in general in young febrile children, in whom the chance of renal involvement is high, it is prudent to choose an antimicrobial to which only a small proportion of organisms are resistant. At the time of writing, the vast majority of uropathogens are sensitive to third-generation cephalosporins.90  In children who are not febrile, it would be more reasonable to use a first-generation cephalosporin, trimethoprim-sulfamethoxazole, or nitrofurantoin.90  Most uropathogens are resistant to amoxicillin, and its use should therefore be avoided. Many studies have revealed that children aged >2 months can be safely managed with oral antibiotics; thus, hospital admission for treatment should be avoided unless the child is unable to tolerate oral antimicrobial therapy. Fever resolves in 68% of children in the first 24 hours and in 92% by 72 hours.91  If fever persists beyond 72 hours, the clinician should reevaluate the diagnosis and decide whether an RBUS is emergently needed to rule out renal abscess. Antibiotic treatment should be started within 48 hours of fever onset because delayed treatment increases the risk of renal scarring.3032  Oral antibiotic therapy for 7 to 10 days is adequate for uncomplicated febrile UTI presumed to be APN that responds well to the treatment. In a recent study, researchers reported that in infants aged <60 days with bacteremic UTI, ≤7 days of parenteral antibiotic therapy may be as safe and effective as conventional, longer-duration treatment.68  In another recent study in children, researchers reported that 6 to 9 days of antibiotic treatment is as effective for treating APN as a longer duration of ≥10 days.69  Routine follow-up urinalysis and culture (so-called proof-of-cure tests) after the resolution of UTI symptoms are not necessary unless clinically indicated.92,93 

The effectiveness of antimicrobial prophylaxis in the prevention of UTI recurrence has been studied extensively. The RIVUR trial revealed that trimethoprim-sulfamethoxazole prophylaxis reduced the risk of UTI recurrence by 50%. Similar results were reported by another placebo-controlled, double-blind (PRIVENT study) trial.94  Combined results of the RIVUR and the Careful Urinary Tract Infection Evaluation (CUTIE) studies revealed that toilet-trained children with VUR and BBD exhibit the greatest benefit from antimicrobial prophylaxis.95  However, many other randomized studies have revealed either a sex-based96  or no97101  beneficial effect with prophylaxis. In systematic reviews and meta-analyses, researchers have also reported mixed results, with some concluding that prophylaxis is effective102,103  and others reporting that prophylaxis offers no or little advantage for the prevention of UTI recurrence.104,105  These variations in results have been attributed to significant differences in study designs, including patient inclusion and exclusion criteria.106  No study has demonstrated any beneficial effect of antimicrobial prophylaxis for the prevention of renal scarring, although one must add that none of these studies were powered to evaluate renal scarring as a primary study end point, and even a recent meta-analysis was likely underpowered to reveal an effect.107 

Antibiotic resistance is a major risk of long-term prophylaxis108  and, hence, should be used selectively.106,109,110  In cases of febrile UTI and VUR, the American Urological Association recommends continuous antibiotic prophylaxis in children aged <1 year and a selective approach in older children based on patient age, severity of VUR, recurrence of UTI, presence of BBD, and renal cortical anomalies.111  The European Association of Urology, European Society of Pediatric Urology, and Swedish and Italian Society of Pediatric Nephrology also recommend a more selective approach based on a combination of patient age, severity of VUR, and renal scarring.112114  Other factors that should be considered before initiating long-term antimicrobial prophylaxis include the status of toilet training, risk of antibiotic resistance, anticipated compliance with daily medication administration, parental choice, and the medication expense. In all recommendations, younger age is a particular consideration for prophylaxis because of a nonspecific clinical presentation for UTI, the difficulty in getting urine specimens, the higher possibility of a need for hospitalization for intravenous antibiotic administration and hydration, an increased risk of septicemia, and family disruption and parental anxiety. In some cases, a preemptive antimicrobial prophylaxis may be necessary to lower the risk of first UTI, such as in those with high-grade VUR diagnosed during workup for antenatal hydronephrosis. The duration of prophylaxis depends on multiple factors and may range from a few days until a VCUG can be obtained in those recently diagnosed with UTI to a few years for children with VUR on medical management.

Secondary analysis of the RIVUR study has revealed that the patients who took trimethoprim-sulfamethoxazole <70% of the time were 2.5 times more likely (95% confidence interval 1.1–5.6) to have a recurrent UTI and were at highest risk for renal scarring (odds ratio 24.2, 95% confidence interval 3.0–197), as compared to most adherent patients.115  It also revealed that the long-term prophylaxis with trimethoprim-sulfamethoxazole was not associated with an increased risk of skin and soft-tissue infections, pharyngitis or sinopulmonary infections,116  or excessive weight gain.117  In another study, researchers reported that routine monitoring of blood chemistry, renal function, or complete blood cell count were not necessary in children receiving long-term trimethoprim-sulfamethoxazole prophylaxis.118  Regarding the cost-effectiveness of antibiotic prophylaxis, one study revealed that the prophylaxis was associated with marginally higher costs, as compared with placebo,119  whereas researchers in another study reported that the prophylaxis was more cost-effective than observation in children with high-grade (grade 4) but not low-grade VUR; this finding should be considered in light of the fact that the large majority of children with VUR do not have high-grade disease.120 

Antibiotic resistance of pathogens causing UTI at any age is a growing concern internationally.121125  As such, there is a need for a judicious use of antibiotics for the prevention and the treatment of UTIs. Some of the measures that could help reduce the risk of antibiotic resistance in children with UTIs are as follows126 :

  • Collection of uncontaminated urine specimen for diagnosis so that patients do not receive an antibiotic for a false-positive urine culture result;

  • Initiation of empirical antibiotic therapy only after collecting an uncontaminated urine specimen to help with the selection of a right antibiotic for continued treatment or its discontinuation, depending on the urine culture results and the patient’s clinical status;

  • Avoiding or deferring the use of antibiotic in a patient suspected of having viral or chemical cystitis;

  • Not using a routine, long-term antimicrobial prophylaxis in low-risk patients; and

  • Not treating ABU with antibiotics.

Few patients diagnosed with VUR after UTI need surgical correction. It is usually reserved for patients with high-grade VUR, recurrent UTI despite antibiotic prophylaxis, and noncompliance with or intolerance of prophylactic antibiotics and for the worsening of renal scars.127  Open ureteral reimplantation remains the mainstay of surgical correction for VUR, although endoscopic treatment is also widely used, particularly for lower-grade VUR. Laparoscopic reimplantation techniques (with or without robotic assistance) have increased in recent years, but use remains limited to specific centers. Endoscopic treatment involves subureteral or intraureteral injection of a bulking agent (most commonly dextranomer and hyaluronic acid [Deflux]). The decision for timing and the type of intervention is based on the age of the patient, status of the kidneys, grade of VUR, and parental wishes.6 

Recurrent UTI can be prevented by preventing constipation and avoidance of urine withholding behavior in toilet-trained children. Although increased oral fluid helps flush bacteria from the bladder, prompts frequent urination, and alleviates constipation, there is limited evidence that it is effective in preventing UTIs.128  In uncircumcised boys, gentle, daily retraction and cleaning should be performed; in boys with phimosis, topical corticosteroid ointment or circumcision may be necessary to prevent UTI recurrence. There is no evidence in children to recommend cranberry juice for the prevention of UTIs. In a systematic review of studies in adults, researchers concluded that given the evidence, cranberry juice cannot currently be recommended for the prevention of UTIs.129 

A good clinical assessment supplemented by laboratory results on an uncontaminated urine specimen is essential for the accurate diagnosis of UTI in children. Renal ultrasound examination is recommended after first UTI in younger children and recurrent UTI in older children. Most children with first febrile UTI do not need a VCUG, but an early VCUG is appropriate in some patients. Prompt antibiotic treatment reduces morbidity and the risk of renal scarring. Oral antibiotic administration for 7 to 10 days is sufficient to eradicate infection in those with a good clinical response. Surveillance urinalysis and culture after UTI are not necessary unless clinically indicated. A selective use of antimicrobial prophylaxis is considered in patients with recurrent UTI and those with a high risk of renal scarring. Careful use of antibiotics is essential for the prevention of drug resistance of pathogens causing UTIs.

Dr Mattoo conceptualized and formatted the manuscript template, drafted the initial manuscript, and reviewed and revised the manuscript; Drs Nelson and Shaikh participated in formatting the initial manuscript, drafted sections of the initial manuscript, and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: No external funding.

     
  • AAP

    American Academy of Pediatrics

  •  
  • ABU

    asymptomatic bacteriuria

  •  
  • APN

    acute pyelonephritis

  •  
  • BBD

    bladder-bowel dysfunction

  •  
  • CAKUT

    congenital anomalies of kidneys and the urinary tract

  •  
  • CFU

    colony-forming unit

  •  
  • DMSA

    dimercaptosuccinic acid

  •  
  • RBUS

    renal bladder ultrasound

  •  
  • RIVUR

    Randomized Intervention for Children with Vesicoureteral Reflux

  •  
  • UTI

    urinary tract infection

  •  
  • VCUG

    voiding cystourethrogram

  •  
  • VUR

    vesicoureteral reflux

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Competing Interests

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