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Urinary tract infections in infants older than one month and young children: Acute management, imaging, and prognosis

Urinary tract infections in infants older than one month and young children: Acute management, imaging, and prognosis
Authors:
Nader Shaikh, MD
Alejandro Hoberman, MD
Section Editors:
Morven S Edwards, MD
Tej K Mattoo, MD, DCH, FRCP
Deputy Editor:
Mary M Torchia, MD
Literature review current through: Dec 2022. | This topic last updated: Apr 22, 2022.

INTRODUCTION — Urinary tract infections (UTI) are a common and important clinical problem in childhood. Upper urinary tract infections (ie, acute pyelonephritis) may lead to renal scarring, hypertension, and end-stage kidney disease. Although children with pyelonephritis tend to present with fever, it can be difficult on clinical grounds to distinguish cystitis from pyelonephritis, particularly in young children (those younger than two years) [1]. Thus, we have defined UTI broadly here without attempting to distinguish cystitis from pyelonephritis. Acute cystitis in older children is discussed separately. (See "Acute infectious cystitis: Clinical features and diagnosis in children older than two years and adolescents".)

The acute management and prognosis of UTI in children will be reviewed here. The epidemiology, risk factors, clinical features, diagnosis, long-term management, and prevention of UTI in children and UTI in newborns are discussed separately. (See "Urinary tract infections in children: Epidemiology and risk factors" and "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis" and "Urinary tract infections in children: Long-term management and prevention" and "Urinary tract infections in neonates".)

OVERVIEW

Goals — The goals of treatment for UTI include [2,3]:

Elimination of infection and prevention of urosepsis

Relief of acute symptoms (eg, fever, dysuria, frequency)

Prevention of recurrence and long-term complications including hypertension, renal scarring, and impaired renal growth and function

Acute management of UTI in children consists of antimicrobial therapy to treat the acute infection and evaluation for possible predisposing factors (eg, urologic abnormalities). Long-term management centers on prevention of recurrence and complications; it is discussed separately. (See "Urinary tract infections in children: Long-term management and prevention".)

Decision to hospitalize — Most children older than two months with UTI can be safely managed as outpatients as long as close follow-up is possible [3-5].

Usual indications for hospitalization and/or parenteral therapy include [3,6-8]:

Age <2 months

Clinical urosepsis (eg, toxic appearance, hypotension, poor capillary refill)

Immunocompromised patient

Vomiting or inability to tolerate oral medication

Lack of adequate outpatient follow-up (eg, no telephone, live far from hospital)

Failure to respond to outpatient therapy (see 'Response to therapy' below)

Although some studies suggest that outpatient management may be considered for select well-appearing infants 29 to 60 days of age [9,10], additional evidence is necessary.

ANTIBIOTIC THERAPY — Antimicrobial therapy for children with presumed UTI depends upon a number of factors, including the age of the child, severity of illness, presence of vomiting, duration of fever before presentation, underlying medical and/or urologic problems, and the antimicrobial resistance patterns in the community.

Risk of UTI — The University of Pittsburgh provides a calculator (UTICalc) to determine the probability of UTI in febrile (temperature ≥38°C [100.4°F]) children age 2 to 24 months based upon their clinical and laboratory results.

Empiric therapy — Early antibiotic therapy (eg, within 72 hours of presentation) may prevent renal damage. In one study, a delay in the treatment of febrile UTIs was associated with increased risk for renal scarring; a delay of 48 hours or more increased the odds of new renal scarring by approximately 47 percent [11]. Although two previous studies failed to show this association, they only evaluated the association between treatment delay and renal scarring in the subset of children with pyelonephritis, which is a limitation [12,13].

Decisions regarding the initiation of empiric antimicrobial therapy for UTI are best made on a case-by-case basis based upon the probability of UTI, which is determined by demographic and clinical factors, and results of the urinalysis [14,15]. (See 'Risk of UTI' above.)

We suggest that empiric antimicrobial therapy be initiated immediately after appropriate urine collection in children with a highly probable UTI based on their clinical and laboratory findings (ie, "high risk" per UTICalc). (See "Urine collection techniques in infants and children with suspected urinary tract infection", section on 'Selection of technique'.)

Early initiation of antimicrobial therapy is particularly important for children who are at increased risk for renal scarring if UTI is not promptly treated, including those who present with:

Fever (especially >39°C [102.2°F] or >48 hours)

Ill appearance

Costovertebral angle tenderness

Known immune deficiency

Known urologic abnormality

Choice of regimen

Antimicrobial spectrum and susceptibility — A Gram-stained smear of the urine, if readily available, can help guide decisions regarding empiric therapy. The ultimate choice of antimicrobial therapy is based upon the susceptibilities of the organism isolated.

Escherichia coli is the most common bacterial cause of UTI; it accounts for approximately 80 percent of UTI in children [16,17]. Other gram-negative bacterial pathogens include Klebsiella, Proteus, Enterobacter, and Citrobacter. Gram-positive bacterial pathogens include Staphylococcus saprophyticus, Enterococcus, and, rarely, Staphylococcus aureus. (See "Urinary tract infections in children: Epidemiology and risk factors", section on 'Microbiology'.)

We recommend that empiric therapy for UTI in infants and children include an antibiotic that provides adequate coverage for E. coli. The agent of choice should be guided by local resistance patterns [18,19].

Approximately 50 percent of E. coli are resistant to amoxicillin or ampicillin [19-25]. In addition, increasing rates of E. coli resistance to first-generation cephalosporins (eg, cephalexin), amoxicillin-clavulanate or ampicillin-sulbactam, and trimethoprim-sulfamethoxazole (TMP-SMX) have been reported in some communities [16,17,19,24,26-28]. Risk factors for resistance to narrow-spectrum antibiotics (eg, amoxicillin, first-generation cephalosporins, nitrofurantoin, TMP-SMX) include lack of circumcision in males, bowel and bladder dysfunction, receipt of antibiotics in the previous six months, and Hispanic ethnicity [18,19,25,28-30]. (See 'Recent antibiotic exposure' below.)

Second or third-generation cephalosporins (eg, cefuroxime, cefpodoxime, cefixime, cefdinir, ceftibuten, cefotaxime, ceftriaxone) and aminoglycosides (eg, gentamicin, amikacin) are appropriate first-line agents for empiric treatment of UTI in most children, particularly those at increased risk of renal involvement (ie, fever >39°C [102.2°F]). First-generation cephalosporins (eg, cephalexin) are reasonable for children at low risk of renal involvement provided that the local resistance of E. coli to first-generation cephalosporins is not increased (eg, is not ≥15 percent). However, cephalosporins are not effective in treating Enterococcus and should not be used as monotherapy for patients in whom enterococcal UTI is suspected (eg, those with a urinary catheter in place, instrumentation of the urinary tract, or an anatomical abnormality). In such patients, amoxicillin or ampicillin should be added. Hydration status and renal function should be assessed in patients who are treated with aminoglycosides.

Oral therapy — Most children who are not vomiting can be treated with orally administered antimicrobials [3,31,32]. Close contact with the caregivers should be maintained for the first two to three days of therapy; the seriousness of the infection and the need for completion of the entire course of therapy should be stressed.

Preferred oral regimens – We suggest a cephalosporin as the first-line oral agent in the treatment of UTI in children without genitourinary abnormalities [4,5,33,34]. Antimicrobial therapy for children with genitourinary abnormalities is individualized.

For children with a high likelihood of renal involvement (ie, fever >39°C [102.2°F] with or without back pain) or immune deficiency, we generally use a second-generation (eg, cefuroxime) or third-generation cephalosporin (eg, cefixime, cefdinir, ceftibuten). The predicted probability of resistance to first-generation cephalosporins, trimethoprim-sulfamethoxazole, or amoxicillin is relatively high, and the tissue concentrations of nitrofurantoin may not be adequate to eradicate the causative organism.

Cefuroxime, cefixime, cefdinir, and ceftibuten are dosed as follows:

-Cefuroxime 30 mg/kg per day by mouth in two divided doses (cefuroxime suspension is not available in the United States)

-Cefixime 8 mg/kg once daily

-Cefdinir 14 mg/kg by mouth once daily

-Ceftibuten 9 mg/kg by mouth once daily

Cefpodoxime 10 mg/kg per day by mouth divided in two doses is another option, but no large trials have specifically evaluated the efficacy of cefpodoxime for pediatric UTI [3,35].

For children with low risk of renal involvement (fever ≤39°C [102.2°F], not toxic-appearing), we prefer a first-generation cephalosporin (eg, cephalexin 50 to 100 mg/kg per day by mouth in two divided doses [35]) provided that the local resistance of E. coli to first-generation cephalosporins in the specific community is not high (eg, is not ≥15 percent). The predicted probability of resistance to trimethoprim-sulfamethoxazole and amoxicillin are relatively high, and nitrofurantoin needs to be given more frequently and is more likely to cause gastrointestinal symptoms [18].

In a randomized, controlled trial of 306 children 1 to 24 months of age with a febrile UTI, oral therapy with cefixime for 14 days was as effective as intravenous (IV) therapy with cefotaxime for three days followed by oral therapy with cefixime [4]. The rates of symptom resolution (mean time to defervescence approximately 24 hours), sterilization of the urine (100 percent), reinfection (4.6 and 7.2 percent), and renal scarring at six months (9.8 and 7.2 percent) did not differ between groups.

A similar trial in children 6 months to 16 years, albeit limited by imbalances in comparability of treatment groups at baseline and high drop-out rates, found once-daily therapy with ceftibuten to be comparable to initial therapy with ceftriaxone followed by ceftibuten [33]. Oral amoxicillin-clavulanate (50 mg/kg per day in three divided doses) also was shown to be as effective as parenteral therapy followed by oral therapy in a multicenter, randomized trial [36]. However, amoxicillin-clavulanate is associated with increasing rates of resistance. In a child with a penicillin and cephalosporin allergy, treatment with TMP-SMX, or ciprofloxacin (if the local resistance rates to TMP-SMX are known to be high) and close follow-up of the antimicrobial sensitivity results is a reasonable strategy.

Amoxicillin and ampicillin are not routinely recommended for empiric therapy because of the high rate of resistance of E. coli. Similarly, amoxicillin-clavulanate and TMP-SMX should be used with caution, especially when pyelonephritis is suspected, because of the increasing rates of resistance to these drugs in some communities [16,18,19,21-24,26,37-39]. The rate of E. coli producing extended spectrum beta-lactamases appears to be increasing [40].

Fluoroquinolones (eg, ciprofloxacin) are effective for E. coli, and resistance in children is rare. However, widespread use of fluoroquinolones is leading to increased resistance among other bacteria [41-43], and ciprofloxacin should not be routinely used as a first-line agent [44]. The American Academy of Pediatrics (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 [45]. (See "Fluoroquinolones", section on 'Children'.)

Parenteral therapy

Inpatient parenteral therapy — In-hospital parenteral therapy generally is indicated for children with [3,6-8]:

Age <2 months (see "Urinary tract infections in neonates")

Clinical urosepsis (eg, toxic appearance, hypotension, poor capillary refill)

Immune compromise

Vomiting or inability to tolerate oral medication

Lack of adequate outpatient follow-up (eg, no telephone, live far from hospital, etc)

Failure to respond to outpatient therapy (see 'Response to therapy' below)

Cephalosporins (eg, cefotaxime, ceftriaxone, cefepime) and aminoglycosides (eg, gentamicin) are appropriate first-line parenteral agents for empiric treatment of UTI in children. Definitive therapy is based upon the results of urine culture and sensitivities.

Acceptable inpatient treatment regimens include the combination of ampicillin and gentamicin; gentamicin alone; or a third- or fourth-generation cephalosporin [46-48]. Ampicillin should be included if enterococcal UTI is suspected. (See 'Recent antibiotic exposure' below.)

The doses are as follows [3,35,49]:

Ampicillin (100 mg/kg/day IV divided in four doses)

Gentamicin (7.5 mg/kg/day IV divided in three doses)

Cefotaxime (150 mg/kg per day IV divided in three or four doses)

Ceftriaxone (50 to 75 mg/kg per day IV)

Cefepime (100 mg/kg per day divided in two doses; maximum daily dose 4g)

Parenteral antibiotics should be continued until the patient is clinically improved (eg, afebrile) and able to tolerate oral liquids and medications [3]. (See 'Duration of therapy' below.)

Outpatient parenteral therapy — Once-daily parenteral administration of gentamicin or ceftriaxone in a day treatment center may avoid the need for hospital admission in select patients (eg, children ≥2 months who are unable to tolerate oral therapy and are nontoxic appearing, well hydrated, without urologic abnormalities, and whose caretakers will be able to adhere to the outpatient regimen) [50-52].

Recent antibiotic exposure — Recent exposure to antibiotics, whether for treatment of an infection or as antimicrobial prophylaxis, is an important consideration in the choice of empiric antibiotic therapy [18,19,29,30,53-57]. Patients who have recently been treated with antibiotics are more likely to have a uropathogen that is resistant to that agent; pending culture and susceptibility results, they may require an antibiotic from a different class [30,58,59]. Antimicrobial prophylaxis for prevention of recurrent UTI is discussed separately. (See 'Prophylactic antibiotics' below and "Urinary tract infections in children: Long-term management and prevention", section on 'Antimicrobial prophylaxis'.)

Recurrent UTI — Review of the antimicrobial susceptibilities of the most recent urinary pathogens can be helpful in choosing empiric therapy for children with recurrent UTI.

Duration of therapy — In a systematic review, short-course antimicrobial therapy (two to four days) was as effective as standard duration (7 to 14 days) therapy in eradicating bacteria in children with suspected lower UTI (ie, afebrile children) [60]. However, little evidence is available to guide duration of antimicrobial therapy in children with febrile UTIs. A large multicenter trial evaluating the efficacy of short-course therapy for UTI in children, sponsored by the National Institutes of Health, has completed enrollment; results are pending [61]. If the trial demonstrates that short-course therapy is efficacious, clinicians may be able to limit the duration of exposure to antimicrobials to that needed to eradicate the offending uropathogen, reducing the likelihood of adverse events and the emergence of bacterial resistance.

In the meantime, we suggest a longer course of therapy for febrile children (usually 10 days) and a short course of therapy (three to five days) for immune-competent children presenting without fever.

Oral antibiotics can be used to complete the course of therapy for patients who are initially treated with parenteral antibiotics. We generally switch to oral antibiotics when the patient is tolerating oral fluids and has been afebrile for 24 hours. There is no minimum duration for parenteral therapy. In retrospective cohort studies in young infants with and without bacteremia, the duration of parenteral antibiotic therapy was not associated with rates of treatment failure or readmission [62-64].

Response to therapy

Clinical response — The clinical condition of most patients improves within 24 to 48 hours of initiation of appropriate antimicrobial therapy [65].

The mean time to resolution of fever is 24 hours, but fever may persist beyond 48 hours [4]. In a review of 288 children younger than two years who were admitted to a tertiary-care children's hospital with febrile UTI, 89 percent were afebrile within 48 hours of antimicrobial therapy [65]. No differences were noted between those who remained febrile >48 hours and those who were afebrile within 48 hours with respect to bacteremia (10 and 8 percent, respectively), hydronephrosis (3 and 5 percent, respectively) and significant vesicoureteral reflux (VUR) (19 and 14 percent, respectively).

In children whose clinical condition (other than persistent fever) worsens or fails to improve as expected within 48 to 72 hours of initiation of antimicrobial therapy, broadening antimicrobial therapy may be indicated if the culture and sensitivity results are not yet available. As an example, most of the empiric regimens suggested above do not provide adequate coverage for Enterococcus, and the addition of ampicillin or amoxicillin may be warranted. (See 'Choice of regimen' above.)

In addition, in children who worsen or fail to improve within 48 to 72 hours, renal and bladder ultrasonography should be performed as soon as possible (to evaluate the presence of a renal abscess or surgically correctable anatomic abnormalities or obstruction) [3,66,67]. (See 'Imaging' below.)

Repeat urine culture — Several observational studies suggest there is little utility in repeating the urine culture in children with UTI who are treated with an antibiotic to which their uropathogen is susceptible [65,68,69].

Accordingly, it is not necessary to routinely obtain repeat urine cultures during antimicrobial therapy to document sterilization of the urine, provided that the child has had the expected clinical response and the uropathogen is susceptible to the antibiotic that is used for treatment [70,71]. However, urine cultures should be performed after 48 hours of therapy if the patient fails to respond clinically or if the uropathogen is not susceptible (intermediate or resistant) to the antibiotic that is being used for treatment. It is important to routinely perform susceptibility testing on the isolated uropathogens to avoid unnecessary delay in administration of appropriate therapy.

Prophylactic antibiotics — We generally do not provide prophylactic antibiotics to children following a first febrile UTI who do not have VUR. Antibiotic prophylaxis for children who have undergone voiding cystourethrogram (VCUG) and have documented VUR (of any grade) is discussed separately. (See 'Voiding cystourethrogram' below and "Management of vesicoureteral reflux".)

The 2011 AAP practice guideline (reaffirmed in 2016) does not recommend prophylactic antimicrobials following the first febrile UTI in children 2 to 24 months [3,72]. The United Kingdom's National Institute for Health and Care Excellence (NICE) guideline for UTI in children indicates that antibiotic prophylaxis should not be routinely recommended in infants and children following their first UTI but may be warranted after recurrent UTI [70]. (See "Urinary tract infections in children: Long-term management and prevention", section on 'Antimicrobial prophylaxis'.)

ADJUNCTIVE THERAPIES — Renal parenchymal inflammation during UTI may lead to renal scarring, although the predisposing factors are not well understood [73]. The role of renal parenchymal inflammation in the development of renal scars, and the potential role of anti-inflammatory agents in preventing renal scars has been evaluated in several studies [74-77]. In a meta-analysis of three placebo-controlled randomized trials including a total of 529 children [76-78], short-term glucocorticoid therapy during antimicrobial treatment for UTI lowered the risk of kidney scarring (12 versus 29 percent; risk ratio 0.57, 95% CI 0.36-0.90), without increased adverse effects (eg, bacteremia, hospitalization) [79]. Additional trials are necessary to confirm these results and to determine the optimum glucocorticoid regimen before adjunctive glucocorticoids are routinely recommended in the treatment of UTI in children.

IMAGING

Rationale — The rationale for imaging in young children with UTI is to identify abnormalities of the genitourinary tract that require additional evaluation or management (eg, obstructive uropathies, dilating vesicoureteral reflux [VUR]). If such abnormalities are detected, steps can be taken to modify the risk of subsequent renal damage (eg, surgical intervention or antibiotic prophylaxis to prevent recurrent UTI).

The ultimate value of detecting anatomic or functional abnormalities of the urinary tract depends upon the effectiveness of the interventions designed to prevent recurrent UTI and renal scarring [80,81]. Evidence to support the utility of routine imaging in reducing long-term sequelae (renal scarring, hypertension, renal failure) is limited [82-86], and there is a lack of consensus about the optimal imaging strategy [3,70,87-89].

Ultrasonography — Renal and bladder ultrasonography (RBUS) is a noninvasive test that can demonstrate the size and shape of the kidneys, the presence of duplication and dilatation of the ureters, and the existence of gross anatomic abnormalities. RBUS can also identify renal or perirenal abscess or pyonephrosis in children with acute UTI who fail to improve with antimicrobial therapy. Although RBUS is not reliable in diagnosing renal scarring or VUR [90-93], abnormalities on RBUS after first UTI are useful in predicting the risk of renal scarring or VUR [86,94]. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux".)

RBUS is estimated to yield management-altering abnormalities (ie, requiring additional evaluation or surgery) in only 1 to 2 percent of cases of first febrile UTI in young children 2 to 24 months of age [1,3,95-97]. The false positive rate is between 2 and 3 percent [3]. The major advantages of RBUS are the lack of exposure to radiation and helpfulness in predicting risk of renal scarring [86].

Indications — Given the potentially large benefit of detecting correctible malformations for a small number of children and the low risk of harm, we suggest RBUS for the following children:

Children younger than two years of age with a first febrile UTI

Children of any age with recurrent febrile UTIs

Children of any age with a UTI who have a family history of renal or urologic disease, poor growth, or hypertension (table 1A-B)

Children who do not respond as expected to appropriate antimicrobial therapy

However, many women have prenatal ultrasonography after 30 to 32 weeks of gestation – a time at which the urinary tract is fully developed; we may elect not to perform RBUS (in children of any age) if prenatal ultrasonography that was performed at a reputable center was normal and the study results are accessible [98,99].

The American Academy of Pediatrics (AAP) recommends RBUS for all infants and children 2 to 24 months following their first febrile UTI [3,72]. The United Kingdom's National Institute for Health and Care Excellence (NICE) guideline on UTI in children recommends RBUS for infants younger than six months and for children older than six months who have atypical or recurrent UTI [70]. They define atypical UTI as serious illness, poor urine flow, abdominal or bladder mass; elevated creatinine, septicemia, infection with an organism other than E. coli, and failure to respond to antibiotics within 48 hours; they define recurrence as ≥2 episodes of upper UTI, one episode of upper UTI plus ≥1 episode of lower UTI, or ≥3 episodes of lower UTI.

Timing — When the RBUS should be performed depends upon the clinical situation [3]. In infants and young children with unusually severe illness or failure to improve as expected after initiation of antimicrobial therapy, RBUS should be performed as soon as possible during the acute phase of illness to identify complications (eg, renal or perirenal abscess, pyonephrosis). However, for infants and young children who respond as expected to appropriate antimicrobial therapy, RBUS should be performed after the acute phase (to reduce the risk of false positive results secondary to renal inflammation during the acute episode) [3,70]. The decision to treat with prophylactic antibiotics pending results of imaging is discussed above. (See 'Prophylactic antibiotics' above.)

Voiding cystourethrogram — The voiding cystourethrogram (VCUG) is the test of choice to establish the presence and degree of VUR. VUR is the retrograde passage of urine from the bladder into the upper urinary tract. It is an important risk factor for renal scarring. Approximately 25 to 30 percent of children (0 to 18 years) with a first UTI have VUR [81,86]. (See 'Prognosis' below and "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux" and "Urinary tract infections in children: Epidemiology and risk factors", section on 'Risk factors for renal scarring'.)

VCUG involves catheterization to fill the bladder with a radiopaque or radioactive liquid and recording of VUR during voiding. VCUG is expensive, invasive, and may miss a significant portion of children who are at risk for renal scarring [81]. The radiation exposure depends upon the technique and equipment used (the pediatric effective dose estimate ranges from 0.03 to 0.3 mSV) [100]. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Diagnosis' and "Radiation-related risks of imaging".)

Indications — Decisions about performing a VCUG in infants and children with UTI must take into consideration the likelihood of VUR, severity of UTI, the importance placed on preventing recurrences, the cost and discomfort of the VCUG, and perceived likelihood of adherence to prophylaxis (if indicated).

Pending results of ongoing cost-effectiveness analysis of the Randomized Intervention for Vesicoureteral Reflux (RIVUR) data, we suggest performance of a VCUG to diagnose VUR in:

Children of any age with two or more febrile UTIs, or

Children of any age with a first febrile UTI and:

Any anomalies on renal ultrasound, or

The combination of temperature ≥39°C (102.2°F) and a pathogen other than E. coli, or

Poor growth or hypertension (table 1A-B).

In a meta-analysis of individual patient data from nine studies including 1280 children (0 to 18 years) with initial UTI, 68 percent of children with Grade IV or V VUR had either abnormal RBUS or the combination of temperature ≥39°C (102.2°F) and a pathogen other than E. coli [86]. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux" and "Management of vesicoureteral reflux".)

For children with a first febrile UTI and without 1) abnormalities on renal ultrasonography, 2) the combination of temperature ≥39°C (102.2°F) and a pathogen other than E. coli, 3) poor growth, or 4) hypertension, a strategy of "watchful waiting" (ie, observation and performance of VCUG with recurrence) seems reasonable [101], particularly if the caregivers would prefer to avoid prophylactic antibiotics. These children are less likely to have VUR and VCUG results likely to affect management.

It remains uncertain whether the benefits of detection and treatment of VUR after the first UTI outweigh the risks. The uncertainty centers on the changing view of the role of VUR in the development of renal damage and progressive kidney disease and the lack of clarity regarding the effectiveness of medical or surgical management of VUR in reducing the risk of renal scarring [81]. Although the risk of renal scarring is increased in children with VUR compared with children without VUR (41 versus 17 percent in a systematic review) and increases with increasing grades of VUR, VUR is neither necessary nor sufficient for the development of renal scars [81,86]. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Loss of renal parenchyma'.)

Early trials comparing antireflux surgery with antimicrobial prophylaxis in children with VUR showed no differences in rates of recurrent UTI or renal scarring [102-105], but the lack of a placebo or observation group precluded determination that either treatment was more effective than no treatment [102-105]. Subsequent randomized trials comparing antimicrobial prophylaxis with no treatment or placebo had inconsistent results regarding recurrence of UTI, but most of these trials were not blinded [95,106-110].

The RIVUR trial addressed many of these issues. It evaluated the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis in preventing febrile or symptomatic UTI recurrences (primary outcome) in 607 children (two months to six years) who were diagnosed with Grade I to IV VUR after a first or second febrile or symptomatic UTI and were followed for two years [59]. Renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance were secondary outcomes. The RIVUR trial demonstrated unequivocally that prophylactic antibiotics decrease the risk of febrile, recurrent UTI (hazard ratio 0.50, 95% CI 0.34-0.74) [59]. Nearly twice as many children receiving placebo than children receiving prophylaxis were categorized as treatment failures (defined by two febrile UTIs, one febrile UTI and three symptomatic UTIs, four symptomatic UTIs, or new or worsening renal scarring). However, antibiotic prophylaxis did not reduce the risk of scarring and was associated with antimicrobial resistance. (See 'Prophylactic antibiotics' above.)

The 2011 AAP clinical practice guideline (reaffirmed in 2016) recommends postponing VCUG until the second febrile UTI in children 2 to 24 months of age unless there are atypical or complex clinical circumstances or the RBUS reveals hydronephrosis, scarring, or other findings suggestive of high-grade (IV or V) VUR or obstructive uropathy [3,72]. The recommendation was reaffirmed after publication of the results of the RIVUR trial [111]. According to the guideline, the benefit of avoiding radiation exposure and discomfort in the majority of patients outweighs delayed detection of a small number of cases of high-grade reflux or surgically correctible abnormalities. However, the guideline acknowledges that caregiver preferences may play a role in the decision to perform VCUG.

The United Kingdom's NICE guideline suggests VCUG for infants <6 months with atypical or recurrent UTI [70]. They define atypical UTI as serious illness, poor urine flow, abdominal or bladder mass, elevated creatinine, septicemia, infection with an organism other than E. coli, and failure to respond to antibiotics within 48 hours; they define recurrence as ≥2 episodes of upper UTI, one episode of upper UTI plus ≥1 episode of lower UTI, or ≥3 episodes of lower UTI. The NICE guidelines also suggest that VCUG may be warranted for children six months to three years with atypical or recurrent UTI and dilation on ultrasonography, poor urine flow, non-E. coli infection, or family history of VUR.

Timing — Although VCUG is often scheduled several weeks after UTI, it may be performed as soon as the patient is asymptomatic [112]. Early imaging (as early as the first week) does not appear to falsely increase the detection of VUR [113]. To avoid the use of prophylactic antibiotics in children without VUR, we prefer to conduct VCUGs during the last days of antimicrobial therapy or immediately after completion of antimicrobial therapy for UTI.

Renal scintigraphy — Renal scintigraphy using technetium Tc-99m succimer (dimercaptosuccinic acid; DMSA) can be used to detect acute pyelonephritis and renal scarring in the acute and chronic settings, respectively [1,3,114]. DMSA is injected intravenously, and uptake by the kidney is measured two to four hours later. Areas of decreased uptake represent pyelonephritis or scarring. DMSA scans are expensive, invasive, and expose children to radiation (the pediatric effective dose estimate ranges from 0.3 to 3 mSV) [100]. (See "Radiation-related risks of imaging".)

The role of renal scintigraphy in the management of children with acute UTI is controversial. Scintigraphy at the time of an acute UTI provides information about the extent of renal parenchymal involvement. In addition, DMSA will identify most (>70 percent) children with moderate to severe VUR (Grade III or higher) [92,115-117]. This observation has prompted some experts to suggest that DMSA be used as the initial imaging test to identify children at higher risk for renal scarring (the "top down" approach) [118].

However, using DMSA as the initial test to identify high-risk children is more expensive and involves greater exposure to radiation [119]. Furthermore, since most young febrile children with UTI have pyelonephritis and a positive DMSA, this strategy may lead to identification of a large number of children who may or may not be at risk for future UTI [1,81]. In a systematic review of 33 studies, approximately 60 percent of children with initial UTI had DMSA scans consistent with acute pyelonephritis in the acute phase of illness, but only 15 percent had renal scarring at follow-up [81]. It is unclear how to best manage children with positive acute-phase DMSA scan. Careful clinical follow-up of all children with UTI may obviate the need for routine DMSA. (See 'Follow-up' below.)

We suggest not using DMSA in the routine evaluation of children with first UTI. This is consistent with the AAP and NICE guidelines [3,70,72].

Some experts recommend DMSA 6 to 12 months after acute infection to detect the formation of scarring which would require follow-up [120,121]. The NICE guidelines recommend DMSA four to six months after acute infection for children younger than three years with atypical or recurrent UTI and for children older than three years with recurrent UTI [70]. They define atypical UTI as serious illness, poor urine flow, abdominal or bladder mass, elevated creatinine, septicemia, infection with an organism other than E. coli, and failure to respond to antibiotics within 48 hours; they define recurrence as ≥2 episodes of upper UTI, one episode of upper UTI plus ≥1 episode of lower UTI, or ≥3 episodes of lower UTI.

FOLLOW-UP — Caregivers of infants and young children who have been treated for a febrile UTI and children with bowel and bladder dysfunction (a risk factor for recurrent UTI) should be instructed to seek prompt evaluation for subsequent febrile illnesses to ensure prompt recognition and treatment of recurrent UTI [3,70,110]. The evaluation of these episodes should include urinalysis and urine culture [1].

Recurrent UTI is a risk factor for renal scarring, and the risk of renal scarring is substantially increased with the second febrile UTI [122]. Identification of children at risk for recurrent febrile UTI and treatment of bowel and bladder dysfunction that predisposes many children to UTI may be more important than identifying anatomic or functional genitourinary abnormalities after the first febrile UTI in preventing renal scarring [3,122].

In post-hoc analysis of two multicenter prospective studies including 345 children age 2 to 71 months with a history of UTI who did not have vesicoureteral reflux and did not receive prophylactic antibiotics, 14.2 percent had ≥2 febrile UTIs [122]. The incidence of renal scarring was 2.8 percent after the first febrile UTI, 26 percent after two febrile UTIs, and 29 percent after three febrile UTIs. Compared with a single febrile UTI, the odds of renal scarring were 11.8 times greater (95% CI 4.1-34.4 times) after two febrile UTIs and 13.7 times greater (95% CI 3.4-54.4 times) after ≥3 febrile UTIs, highlighting the importance of identifying children at increased risk for a second febrile UTI.

Primary care follow-up for infants and young children who have had a febrile UTI should include regular monitoring of height, weight, and blood pressure. (See "Chronic kidney disease in children: Clinical manifestations and evaluation", section on 'Clinical manifestations'.)

INDICATIONS FOR REFERRAL — Indications for referral to a nephrologist or urologist with expertise in children include [70]:

Recurrent UTI

Dilating vesicoureteral reflux (Grades III to V) or any other congenital renal abnormality

Renal abnormalities

Impaired kidney function

Elevated blood pressure

Bowel and bladder dysfunction refractory to primary care measures (see "Urinary tract infections in children: Long-term management and prevention", section on 'Identify and treat bowel and bladder dysfunction')

PROGNOSIS — The short-term outcome of first UTI in children (<19 years) was described in a systematic review of 33 studies, including 4891 children [81]:

Twenty-five percent had vesicoureteral reflux (VUR); 2.5 percent had Grade IV or V VUR

VUR was associated with an increased risk of developing acute pyelonephritis (relative risk [RR] 1.5, 95% CI 1.1-1.9) and renal scarring (RR 2.6, 95% CI 1.7-3.9); Grade III or higher VUR was associated with increased risk of renal scarring compared with lower grades (RR 2.1, 95% CI 1.4-3.2)

Fifteen percent (95% CI 11-18 percent) of children had evidence of renal scarring on follow-up dimercaptosuccinic acid (DMSA) scan (5 to 24 months later); the long-term significance of scarring, as identified by DMSA, remains to be determined

Eight percent (95% CI 5-11 percent) of children had at least one recurrence

Recurrence among children younger than six years was more likely among White children (hazard ratio [HR] 2.0), those age three to five years (HR approximately 2.5), and those with Grade IV to V VUR (HR 4.38) [56].

Predicting which children with UTI will develop long-term sequelae remains difficult. A systematic review of the literature found only four prospective, relatively small studies addressing this question [123]. The large majority of children with UTI have no long-term sequelae, as illustrated by the following studies:

In a study of 111 high-risk females who were followed for 6 to 32 years after their initial UTI, only seven (6 percent) had decreased glomerular filtration rate (GFR), and none developed end-stage kidney disease [124].

In another study of 68 children with history of urographic renal scarring who were followed for 16 to 26 years after their index UTI, median GFR [82] and mean 24-hour ambulatory blood pressure [125] were no different in children with and without urographic renal scarring. No child developed end-stage kidney disease.

In a study of 226 children with UTI followed for 1 to 41 years, two developed chronic kidney disease that appeared to be attributable to the UTIs [126].

The prognosis for children with nonfebrile UTI is discussed separately. (See "Acute infectious cystitis: Management and prognosis in children older than two years and adolescents", section on 'Prognosis'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Urinary tract infections in children".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

Basics topic (see "Patient education: Urinary tract infections in children (The Basics)")

Beyond the Basics topic (see "Patient education: Urinary tract infections in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Decision to hospitalize – Most children with urinary tract infection (UTI) can be managed as outpatients. Indications for hospitalization include age <2 months, clinical urosepsis, immunocompromised patient, vomiting or inability to tolerate oral medication, lack of outpatient follow-up, and failure to respond to outpatient therapy. (See 'Decision to hospitalize' above.)

Empiric antimicrobial therapy – Empiric antimicrobial therapy immediately after appropriate urine collection is warranted in children with a high probability of UTI based on the clinical and laboratory data available (ie, "high risk" per UTICalc). This is particularly true for young children with fever (especially if >39°C [102.2°F] or >48 hours), ill appearance, costovertebral angle tenderness, known immune deficiency, or known urologic abnormality. (See 'Empiric therapy' above.)

We recommend that empiric therapy for UTI in children include an antibiotic that provides adequate coverage for Escherichia coli (Grade 1B). The agent of choice should be guided by local resistance patterns. Definitive therapy is based upon the results of urine culture and sensitivities. (See 'Choice of regimen' above.)

We suggest a cephalosporin as the first-line oral agent in the treatment of UTI in children without genitourinary abnormalities (Grade 2A). Amoxicillin or ampicillin should be added if enterococcal infection is suspected. (See 'Oral therapy' above.)

-For children with a high likelihood of renal involvement (ie, fever >39°C [102.2°F] with or without back pain), we use a second-generation (eg, cefuroxime) or third-generation cephalosporin (eg, cefixime, cefdinir, ceftibuten).

-For children with low risk of renal involvement (eg, fever ≤39°C [102.2°F], not toxic-appearing), we prefer a first-generation cephalosporin (eg, cephalexin) provided that the local resistance of E. coli to first-generation cephalosporins is not increased.

Cephalosporins (eg, cefotaxime, ceftriaxone, cefepime) and aminoglycosides (eg, gentamicin) are appropriate first-line parenteral agents for empiric treatment of UTI in children. (See 'Parenteral therapy' above.)

Duration of therapy – The duration of therapy depends upon the age of the child and the clinical scenario. (See 'Duration of therapy' above.)

Febrile children are usually treated for 10 days

Afebrile children are usually treated for shorter periods (3 to 5 days) (see 'Duration of therapy' above and "Acute infectious cystitis: Clinical features and diagnosis in children older than two years and adolescents")

Response to therapy – The clinical condition of most patients improves within 24 to 48 hours of initiation of appropriate antimicrobial therapy. (See 'Clinical response' above.)

In children whose clinical condition worsens or fails to improve as expected within 48 to 72 hours of initiation of antimicrobial therapy, broadening of empiric therapy may be indicated. Renal bladder ultrasonography (RBUS) should be performed as soon as possible to evaluate the presence of renal abscess or surgically correctable anatomic abnormalities or obstruction. (See 'Clinical response' above.)

Imaging

RBUS – We obtain routine RBUS after first febrile UTI in children younger than two years who did not have normal prenatal ultrasonography at a reputable center at >30 to 32 weeks of gestation. We also obtain RBUS for children of any age with recurrent febrile UTIs and children of any age with a first UTI who have poor growth, hypertension, or a family history of renal or urologic disease. (See 'Ultrasonography' above.)

VCUG – We obtain voiding cystourethrogram (VCUG) to diagnose vesicoureteral reflux (VUR) in children of any age with ≥2 febrile UTIs. We also obtain VCUG in children of any age with a first febrile UTI and:

-Any anomalies on renal ultrasound, or

-The combination of temperature ≥39°C (102.2°F) and a pathogen other than E. coli, or

-Poor growth or hypertension. (See 'Voiding cystourethrogram' above.)

Prognosis – The majority of children with UTI have no long-term sequelae. Prediction of long-term sequelae in children with UTI remains difficult. (See 'Prognosis' above.)

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