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

INTRODUCTION — Urinary tract infections (UTI) are a common and important clinical problem in childhood. Upper urinary tract infections (ie, acute pyelonephritis) may lead to kidney 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, kidney scarring, and impaired kidney 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".)

DETERMINING NEED FOR EARLY EMPIRIC ANTIBIOTIC THERAPY — We suggest that empiric antimicrobial therapy be initiated immediately in children with a strongly suspected UTI, particularly for those at increased risk for kidney scarring. Suspicion for UTI is based upon demographic and clinical factors (eg, age, sex assigned at birth, circumcision status) and results of the urinalysis (eg, nitrites, leukocyte esterase, white blood cells, and red blood cells) [4,5]. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Decision to obtain urine sample'.)

It is important to collect urine to send for culture and susceptibility before initiating empiric therapy. Routine susceptibility testing on the isolated uropathogens will prevent unnecessary delay in administration of definitive therapy.

Early initiation of antimicrobial therapy is particularly important for children who are at increased risk for kidney scarring if UTI is not promptly treated, including those who present with one or more of the following:

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

●Ill appearance

●Costovertebral angle tenderness

●Known immune deficiency

●Known urologic abnormality (eg, Grade IV or V vesicoureteral reflux)

Early antibiotic therapy (eg, within 72 hours of presentation) may prevent kidney damage. In one study, a delay in the treatment of febrile UTIs was associated with increased risk for kidney scarring; a delay of 48 hours or more increased the odds of new kidney scarring by approximately 47 percent [6].

DETERMINING TREATMENT SETTING — Most children older than two months with UTI who are not vomiting can be safely managed as outpatients as long as close follow-up is possible [7-12]. Close communication 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 emphasized. (See 'Preferred empiric oral regimens' below.)

Usual indications for hospitalization and/or parenteral therapy (see 'Parenteral antibiotics' below) include any of the following [11,13-15]:

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

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

●Immunocompromised febrile patients

●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 [16,17], additional evidence is necessary.

CHOICE OF ANTIBIOTICS

Recent antibiotic exposure — Children receiving antibiotic prophylaxis who have breakthrough UTIs should be treated with a different antimicrobial agent because the organisms are often resistant to the prophylactic antibiotic. Similarly, patients who have been treated with antibiotics for an acute infection within the last two months are also 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 [18-28]. (See 'Second-line empiric oral regimens' below.)

Preferred empiric oral regimens — We recommend a cephalosporin as the first-line oral agent in the treatment of UTI in children (algorithm 1) [7,8,29,30].

The antibiotic of choice should also be guided by local resistance patterns [18,19]; in the United States, these are often available from the antimicrobial stewardship committee of the hospital. The most common bacterial cause of UTI in infants and children is Escherichia coli, and approximately 50 percent of E. coli are resistant to amoxicillin or ampicillin [19,31-36] (see "Urinary tract infections in children: Epidemiology and risk factors", section on 'Microbiology'). Furthermore, the frequency of E. coli-producing extended-spectrum beta-lactamases appears to be increasing [37], resulting in higher rates of resistance to amoxicillin-clavulanate. Rates of resistance to trimethoprim-sulfamethoxazole (TMP-SMX) are also increasing in some communities [18,19,32-35,38-42].

Kidney involvement should be suspected if the child has abnormal urinary findings and one or more of the following:

●High fever (≥39°C [102.2^oF])

●Immune deficiency

●Back pain

●Costovertebral angle tenderness

Empiric treatment differs according to whether kidney involvement is suspected.

●Likely kidney involvement – For children with a high likelihood of kidney involvement, we suggest a third-generation cephalosporin (eg, cefdinir, cefixime, ceftibuten) (algorithm 1). The predicted probability of resistance to first-generation cephalosporins, TMP-SMX, and amoxicillin-clavulanate is relatively high [19,35,38,42-45], and the tissue concentrations of nitrofurantoin may not be adequate to eradicate the causative organism.

We use one of the following agents:

•Cefdinir 14 mg/kg by mouth once daily or in two divided doses

•Cefixime 8 mg/kg by mouth once daily or in two divided doses

•Ceftibuten 9 mg/kg by mouth once daily

Antibiotics are given for 10 days unless urine culture antibiotic susceptibilities demonstrate resistance to the empiric antibiotic chosen. The antibiotic would then need to be changed and treatment with the new antibiotic provided for 10 days. (See 'Second-line empiric oral regimens' below.)

If the patient has an allergy to cephalosporins or received a cephalosporin in the past two months, start empiric therapy with a second-line empiric antibiotic. (See 'Second-line empiric oral regimens' below.)

The effectiveness of oral antibiotics for the treatment of febrile patients with UTI has been demonstrated in two randomized trials. In a 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 3 days followed by oral therapy with cefixime [7]. The rates of symptom resolution and sterilization of the urine (100 percent both groups) were the same; differences in the rates of reinfection (4.6 and 7.2 percent) and kidney scarring at 6 months (9.8 and 7.2 percent) were not statistically significant. A similar trial in children 6 months to 16 years diagnosed with pyelonephritis found that the rate of renal scarring among patients treated for 14 days with oral ceftibuten was comparable to those treated with 3 days of IV ceftriaxone followed by 11 days of ceftibuten [29].

●Unlikely kidney involvement – For children with a low likelihood of kidney involvement, we prefer cephalexin 50 to 100 mg/kg per day by mouth in two divided doses for five days, provided that the local resistance of E. coli to first-generation cephalosporins in the specific community is not high (eg, is not ≥15 percent). If local resistance to cephalosporins is high, one of the second-line antibiotics should be chosen based on local resistance patterns (algorithm 1). (See 'Second-line empiric oral regimens' below.)

In a trial of 664 children, aged 2 months to 10 years, with confirmed UTI, those who clinically improved by day 5 of oral antibiotics were randomly assigned to discontinue antibiotics versus complete a 10 day antibiotic course [46]. Treatment failure, defined as a symptomatic UTI on or before a follow-up visit on day 11 through 14, occurred in less than 5 percent of those assigned to short-course therapy and was similar between groups (4.2 versus 0.6 percent).

Once culture results become available, if the pathogen is resistant to empiric therapy, the authors would change the antibiotic to one to which the pathogen is sensitive. However, other experts would not change therapy if the child was clinically improving [47].

Second-line empiric oral regimens

●Allergy to or recent use of a cephalosporin – In patients with recent use of a cephalosporin or an allergy to cephalosporins, options include TMP-SMX, nitrofurantoin, amoxicillin-clavulanate, and ciprofloxacin. However, nitrofurantoin should not be used if kidney involvement is likely because its tissue concentration may not be adequate. (See "Cephalosporin hypersensitivity: Clinical manifestations and diagnosis", section on 'Immediate versus delayed reactions' and "Cephalosporin hypersensitivity: Clinical manifestations and diagnosis", section on 'Challenge procedures'.)

•Amoxicillin-clavulanate 50 mg/kg per day by mouth (dosed by the amoxicillin component) in two or three divided doses (maximum 500 mg/dose)

•TMP-SMX 8 to 12 mg/kg per day of TMP by mouth in two divided doses (maximum 60 to 100 mg every 6 hours)

•Nitrofurantoin 5 to 7 mg/kg per day by mouth divided every 6 hours (50 to 100 mg every 6 hours)

•Ciprofloxacin 10 to 20 mg/kg per dose by mouth every 12 hours (maximum 750 mg/dose)

Ciprofloxacin use should be limited to reduce development of resistance among other bacteria. However, if kidney involvement is suspected, ciprofloxacin is the preferred second-line agent. Amoxicillin-clavulanate and TMP-SMX should be used with caution when kidney involvement is likely because these patients are at risk for renal scarring and resistance rates to these two agents are high.

Once culture results become available, if the pathogen is resistant to empiric therapy, the authors would change the antibiotic to one to which the pathogen is sensitive. However, other experts would not change therapy if the child was clinically improving [47].

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 [48-50], and ciprofloxacin should not be routinely used as a first-line agent when other options exist [51]. It has been recommended that the use of ciprofloxacin for UTI in children be limited to UTI caused by multidrug-resistant, gram-negative bacteria [52]. (See "Fluoroquinolones", section on 'Children'.)

Parenteral antibiotics — Cephalosporins (eg, cefotaxime, ceftriaxone) [53-55] and aminoglycosides (eg, gentamicin) are appropriate first-line parenteral agents for empiric treatment of UTI in children (algorithm 1). Definitive therapy is based upon the results of urine culture and sensitivities.

We suggest one of these cephalosporins:

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

●Ceftriaxone (50 to 75 mg/kg per day IV; maximum daily dose 2 g)

If allergy to cephalosporins exists:

●Gentamicin (7.5 mg/kg per day IV divided in three doses); hydration status and kidney function should be assessed and monitored in patients who are treated with aminoglycosides. Aminoglycoside dosing and monitoring are different in children with impaired kidney function. (See "Dosing and administration of parenteral aminoglycosides".)

The treatment course is usually 10 days [11]. 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 clinically improved, is tolerating oral fluids, and has been afebrile for 24 hours [11]. 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 [56-58].

Once culture results become available, if the pathogen is resistant to empiric therapy, the authors would change the antibiotic to one to which the pathogen is sensitive. However, other experts would not change therapy if the child was clinically improving [47].

RESPONSE TO THERAPY

Clinical response — The clinical condition of most patients improves within 24 to 48 hours of initiation of appropriate antimicrobial therapy [59]. 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, the patient should be admitted for parenteral therapy. 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 (algorithm 1). (See 'Determining treatment setting' above and 'Parenteral antibiotics' above.)

Additionally, kidney and bladder ultrasonography should be performed as soon as possible to evaluate for the presence of a kidney abscess [3,60,61]. This is usually performed upon admission. (See 'Imaging' below.)

Although the mean time to resolution of fever is 24 hours, fever may persist beyond 48 hours [7]. 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 [59]. 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 (19 and 14 percent, respectively).

Repeat urine culture — We do not routinely repeat urine cultures. 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 [59,62,63]. 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 [64,65].

PROPHYLACTIC ANTIBIOTICS — The indications for prescribing prophylactic antibiotics are discussed elsewhere. (See "Urinary tract infections in children: Long-term management and prevention", section on 'Antimicrobial prophylaxis' and "Management of vesicoureteral reflux", section on 'Antibiotic prophylaxis'.)

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 UTI recurrence and kidney 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 kidney scarring [66,67]. Evidence to support the utility of routine imaging in reducing long-term sequelae (kidney scarring, hypertension, kidney failure) is limited [68-72], and there is a lack of consensus about the optimal imaging strategy [3,64,73-75].

Ultrasonography — Kidney and bladder ultrasonography (KBUS) 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. KBUS can also identify kidney or perirenal abscess or pyonephrosis in children with acute UTI who fail to improve with antimicrobial therapy. Although KBUS is not reliable in diagnosing kidney scarring or VUR [76-79], abnormalities on KBUS after first UTI are useful in predicting the risk of kidney scarring or VUR [72,80]. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux".)

KBUS is estimated to yield management-altering abnormalities (ie, requiring additional evaluation or surgery) in 1 to 3 percent of cases of first febrile UTI in young children 2 to 24 months of age [1,3,81-84]. The false positive rate is between 2 and 3 percent [3]. The major advantages of KBUS are the lack of exposure to radiation and helpfulness in predicting risk of kidney scarring [72].

Indications — Given the potentially large benefit of detecting malformations in a small number of children and the low risk of harm, we suggest KBUS 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 kidney or urologic disease, poor growth, or hypertension (table 1A-B)

●Children who do not respond as expected to appropriate antimicrobial therapy

However, prenatal ultrasonography is often performed after 30 to 32 weeks of gestation – a time at which the urinary tract is fully developed; we may elect not to perform KBUS (in children of any age) if prenatal ultrasonography that was performed at a reputable center was normal and the study results are accessible [85,86].

The American Academy of Pediatrics (AAP) recommends KBUS for all infants and children 2 to 24 months following their first febrile UTI [3,11]. The United Kingdom's National Institute for Health and Care Excellence (NICE) guidelines on UTI in children recommend KBUS for infants younger than six months and for children older than six months who have atypical or recurrent UTI [64]. 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, 1 episode of upper UTI plus ≥1 episode of lower UTI, or ≥3 episodes of lower UTI.

Timing — When the KBUS 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, KBUS should be performed as soon as possible during the acute phase of illness to identify complications (eg, kidney or perirenal abscess, pyonephrosis). However, for infants and young children who respond as expected to appropriate antimicrobial therapy, KBUS should be performed after the acute phase (to reduce the risk of false positive results secondary to kidney inflammation during the acute episode) [3,64]. The decision to treat with prophylactic antibiotics pending results of imaging is discussed elsewhere. (See "Urinary tract infections in children: Long-term management and prevention", section on 'Antimicrobial prophylaxis' and "Management of vesicoureteral reflux", section on 'Antibiotic prophylaxis'.)

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 kidney scarring. Approximately 25 to 30 percent of children (0 to 18 years) with a first UTI have VUR [67,72]. (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 kidney scarring [67]. The radiation exposure depends upon the technique and equipment used (the pediatric effective dose estimate ranges from 0.03 to 0.3 millisieverts) [87]. (See "Radiation-related risks of imaging" and "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Diagnosis'.)

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 kidney 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 KBUS or the combination of temperature ≥39°C (102.2°F) and a pathogen other than E. coli [72]. (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 kidney 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 [88], 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 kidney 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 kidney scarring [67]. Although the risk of kidney 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 kidney scars [67,72]. (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 kidney scarring [89-92], but the lack of a placebo or observation group precluded determination that either treatment was more effective than no treatment [89-92]. 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 [81,93-97].

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 [28]. Kidney 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) [28]. 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 kidney 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 guidelines (reaffirmed in 2016) recommend 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 KBUS reveals hydronephrosis, scarring, or other findings suggestive of high-grade (IV or V) VUR or obstructive uropathy [3,11]. The recommendation was reaffirmed after publication of the results of the RIVUR trial [98]. According to the guidelines, 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 guidelines acknowledge that caregiver preferences may play a role in the decision to perform VCUG.

The United Kingdom's NICE guidelines suggest VCUG for infants <6 months with atypical or recurrent UTI [64]. 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 [99]. Early imaging (as early as the first week) does not appear to falsely increase the detection of VUR [100]. 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.

Kidney scintigraphy — Kidney scintigraphy using technetium Tc-99m succimer (dimercaptosuccinic acid [DMSA]) can be used to detect acute pyelonephritis and kidney scarring in the acute and chronic settings, respectively [1,3,101]. 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 millisieverts) [87]. (See "Radiation-related risks of imaging".)

The role of kidney 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 kidney parenchymal involvement. In addition, DMSA will identify most (>70 percent) children with moderate to severe VUR (Grade III or higher) [78,102-104]. This observation has prompted some experts to suggest that DMSA be used as the initial imaging test to identify children at higher risk for kidney scarring (the "top down" approach) [105].

However, using DMSA as the initial test to identify high-risk children is more expensive and involves exposure to radiation [106]. 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 [1,67]. 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 kidney scarring at follow-up [67]. 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 [3,11,64].

Some experts recommend DMSA 6 to 12 months after acute infection to detect the formation of scarring which would require follow-up [107,108]. 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 [64]. 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 [3,64,97]. The evaluation of these episodes should include urinalysis and urine culture [1].

Recurrent UTI is a risk factor for kidney scarring, and the risk of kidney scarring is substantially increased with the second febrile UTI [109]. 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 kidney scarring [3,109].

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 [109]. The incidence of kidney 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 kidney 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 [64]:

●Recurrent UTI

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

●Other kidney 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 [67]:

●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 kidney scarring (RR 2.6, 95% CI 1.7-3.9); Grade III or higher VUR was associated with increased risk of kidney 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 kidney 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) [25].

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 [110]. 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 7 (6 percent) had decreased glomerular filtration rate (GFR), and none developed end-stage kidney disease [111].

●In another study of 68 children with history of urographic kidney scarring who were followed for 16 to 26 years after their index UTI, median GFR [68] and mean 24-hour ambulatory blood pressure [112] were no different in children with and without urographic kidney scarring. No child developed end-stage kidney disease.

●In a study of 226 children with UTI followed for 1 to 41 years, 2 developed chronic kidney disease that appeared to be attributable to the UTIs [113].

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 5^th to 6^th 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 10^th to 12^th 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, febrile immunocompromised patient, vomiting or inability to tolerate oral medication, lack of reliable outpatient follow-up, and failure to respond to outpatient therapy. (See 'Determining treatment setting' above.)

●Empiric oral antimicrobial therapy – Following appropriate urine collection, immediate initiation of empiric antimicrobial therapy is warranted in children with a high probability of UTI based on available clinical and laboratory data (algorithm 1). This is particularly true for young children with any features that suggest likely kidney involvement, including (see 'Determining need for early empiric antibiotic therapy' above):

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

•Ill appearance

•Costovertebral angle tenderness

•Known immune deficiency

•Known urologic abnormality (eg, Grade IV or V vesicoureteral reflux [VUR])

In children with suspected UTI, we suggest a cephalosporin as the first-line oral agent rather than other antibiotics such as amoxicillin or trimethoprim-sulfamethoxazole (TMP-SMX) (Grade 2C). Cephalosporins are effective against Escherichia coli, which is the most common pathogen. The agent of choice should be guided by local resistance patterns. (See 'Preferred empiric oral regimens' above.)

•For children with likely kidney involvement, we use a third-generation cephalosporin (eg, cefdinir, cefixime, ceftibuten) and treat for 10 days.

•For children with unlikely kidney involvement, we prefer a 5-day course of a first-generation cephalosporin (eg, cephalexin) provided that the local resistance of E. coli to first-generation cephalosporins is not increased.

In patients with recent use of a cephalosporin or a cephalosporin allergy, alternatives include TMP-SMX, nitrofurantoin, amoxicillin-clavulanate, or ciprofloxacin with the following exceptions: Nitrofurantoin should not be used if kidney involvement is likely because tissue concentrations may not be adequate to eradicate the causative organism, and ciprofloxacin use should be limited to reduce development of resistance among other bacteria. (See 'Second-line empiric oral regimens' above.)

Definitive therapy is based upon the results of urine culture and sensitivities. (See 'Choice of antibiotics' above.)

●Empiric parenteral antimicrobial therapy (hospitalized patients) – In children with suspected UTI who require parenteral antibiotics, we suggest a third-generation cephalosporin (eg, cefotaxime, ceftriaxone) rather than a first generation cephalosporin (Grade 2C). (See 'Parenteral antibiotics' above.)

In patients with recent use of a cephalosporin or cephalosporin allergy, an aminoglycoside, such as gentamicin, is an alternative.

●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.)

•Children whose clinical condition worsens or fails to improve as expected within 48 to 72 hours of initiation of antimicrobial therapy should be admitted to the hospital for parenteral therapy.

•Kidney bladder ultrasonography (KBUS) should be performed as soon as possible following hospital admission to evaluate for the presence of a renal abscess.

●Imaging

•KBUS – We obtain routine KBUS 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 KBUS 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 kidney or urologic disease. (See 'Ultrasonography' above.)

•VCUG – We obtain voiding cystourethrogram (VCUG) to diagnose 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 kidney 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.)