Urinary tract infections in neonates

INTRODUCTION — 

Urinary tract infection (UTI) in neonates (infants ≤30 days of age) is associated with bacteremia and congenital anomalies of the kidney and urinary tract (CAKUT). Upper tract infections (ie, acute pyelonephritis) may result in kidney parenchymal scarring and chronic kidney disease. Neonates with UTI should be evaluated for associated systemic infection and anatomic or functional abnormalities of the kidneys and urinary tract.

The epidemiology, pathogenesis, clinical features, diagnosis, and management of UTIs in neonates will be reviewed here. UTIs in older infants are discussed separately. (See "Urinary tract infections in infants older than one month and children younger than two years: Clinical features and diagnosis" and "Urinary tract infections in infants older than one month and children younger than two years: Acute management, imaging, and prognosis".)

EPIDEMIOLOGY — 

Reported prevalence rates of UTI among neonates and young infants who undergo evaluation due to fever or other concern for infection vary depending on the population studied:

●Neonates undergoing sepsis evaluation during the birth hospitalization – In this setting, UTI most commonly occurs as a complication associated with prematurity or other medical conditions that prolong the birth hospitalization.  

•Early-onset sepsis (<72 hours after birth) – UTI is uncommon in the first few days after birth. A positive urine culture in this setting reflects high-grade bacteremia rather than an isolated UTI. Thus, urine cultures are not routinely included in the evaluation for early-onset sepsis. This is discussed separately. (See "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at or after 35 weeks gestation", section on 'Urine culture'.)

•Late-onset sepsis (≥72 hours after birth) – Among neonates admitted to the neonatal intensive care unit (NICU) who undergo evaluation for late-onset sepsis, the urine culture is positive in approximately 10 to 15 percent [1-3]. Risk factors for UTI in this population include lower gestational age, longer duration of NICU stay, and the presence of invasive devices, especially urinary catheters. (See 'Host factors' below and "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at less than 35 weeks gestation".)

●Febrile young infants undergoing evaluation in the emergency department or outpatient setting – Among young infants presenting to the emergency department or outpatient clinic with fever, reported rates of UTI range from approximately 10 to 20 percent [4-6]. (See "The febrile neonate (28 days of age or younger): Outpatient evaluation", section on 'Infection source and common pathogens' and "The febrile infant (29 to 90 days of age): Outpatient evaluation", section on 'Pathogens and type of infections'.)

MICROBIOLOGY

●Term infants – In term infants who present with community-acquired infection, Escherichia coli is the most common pathogen accounting for approximately 80 to 90 percent of infections in most large series [2,4,7,8]. Other gram-negative bacterial causes of UTI include Klebsiella, Proteus, Enterobacter, and Citrobacter. Gram-positive pathogens include Staphylococcus coagulase-negative species, Enterococcus, and, rarely, Staphylococcus aureus.

●Preterm infants – In hospitalized preterm infants with UTIs, E. coli remains and important pathogen; however, coagulase-negative Staphylococcus and Klebsiella are also common pathogens [9,10]. Candida species are also frequent urinary pathogens in preterm infants, particularly in extremely low birth weight infants (birth weight <1000 g) and those receiving prolonged antibiotic therapy [2]. (See "Candida infections in neonates: Epidemiology, clinical manifestations, and diagnosis", section on 'Urinary tract infection'.)

PATHOGENESIS

●Term infants – Most UTIs in neonates represent upper tract infection (pyelonephritis) rather than simple cystitis. Hematogenous spread of infection had been considered to be responsible for UTI because of the higher frequency of febrile UTI (ie, pyelonephritis), which was presumed to be due to bacteremia. However, increasingly, it is thought that neonatal UTI in term infants is primarily due to ascending infection rather than hematogenous spread from a remote source because of the microbiology of these infections (eg, E. coli) and the high incidence of urinary tract abnormalities. (See 'Host factors' below.)

Several virulence factors in E. coli account for the propensity of this organism to cause UTI, especially when the urinary tract is anatomically abnormal [11]. The best studied virulence factor in E. coli is adhesins located on the tip of bacterial fimbriae (also called pili) or bacterial surface, which facilitate bacterial attachment to the uroepithelium. This allows the bacteria to effectively adhere to the uroepithelium and ascend into the kidney. (See "Bacterial adherence and other virulence factors for urinary tract infection".)

●Preterm infants – Hematogenous infection likely plays a greater role in preterm infants with UTI as there is a higher concordance rate of bacteremia than in term infants. In one large cohort study based on data from Pediatrix Medical neonatal intensive care units, there was a 13 percent rate of a positive blood culture collected within three days of the urine culture with the same pathogenic organism [12].

HOST FACTORS — 

A variety of host factors influence the predisposition to UTI in neonates.

●Male infants – Male infants account for three-quarters of neonates and young infants (<3 months of age) with UTIs [4,13]. This preponderance reflects the higher incidence of urinary tract anomalies in males and the increased risk of UTI in uncircumcised males.

●Uncircumcised males – The incidence of UTI is 10-fold greater in uncircumcised versus circumcised males. This was illustrated in a study of approximately 136,000 male neonates that reported rates of UTI in 0.19 percent of uncircumcised boys versus 0.02 percent in those who were circumcised [14]. The higher incidence of UTI in uncircumcised males is related to an increased rate of bacterial colonization and enhanced bacterial adherence. The increased incidence in uncircumcised males persists during the first year after birth. Parents of newborn males should be provided with accurate information regarding the potential risks and benefits of circumcision (eg, lower risk of UTI) in order to make an informed decision. (See "Neonatal circumcision: Risks and benefits", section on 'Reduction in urinary tract infection' and "Neonatal circumcision: Risks and benefits", section on 'Potential disadvantages'.)

●Prematurity – Preterm infants are at higher risk for developing UTI compared with term infants because of their relatively immunocompromised status and the use of invasive devices (eg, urinary catheters) [9]. (See "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at less than 35 weeks gestation", section on 'Risk factors associated with prematurity'.)

●Kidney and urinary tract abnormalities – Kidney and urinary tract abnormalities are commonly identified in both term and preterm neonates with UTI.

•Term infants – Abnormalities are seen on ultrasound in 35 to 50 percent of neonates and young infants (<3 months of age) with UTI. The most common findings are pelviectasis and mild hydronephrosis [4,7,13,15,16]. Major kidney or urologic abnormalities (ie, high-grade hydronephrosis/vesicoureteral reflux [VUR] and/or other important structural abnormalities) are found in approximately 5 to 10 percent of infants [4,7,13,15,16]. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux".)

In a case series of 95 term neonates with UTI who underwent kidney ultrasound imaging, 45 had a kidney anatomic abnormality including 19 with pelviectasis and 26 with hydronephrosis (graded as mild in 12 cases and moderate in 14 cases) [4]. Voiding cystourethrogram (VCUG) performed in 21 of 26 patients with hydronephrosis demonstrated VUR in five patients.

Other kidney and urinary tract abnormalities associated with neonatal UTI include:

-Urinary obstructive lesions (eg, ureteropelvic junction or ureterovesical junction obstruction, posterior urethral valves) (see "Clinical presentation and diagnosis of posterior urethral valves", section on 'Postnatal' and "Congenital ureteropelvic junction obstruction", section on 'Clinical presentation')

-Ectopic ureter (see "Ectopic ureter", section on 'Postnatal presentation')

-Parenchymal kidney disorders (eg, polycystic diseases, kidney dysplasia) (see "Autosomal recessive polycystic kidney disease in children", section on 'Kidney manifestations' and "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Renal dysplasia and hypodysplasia')

Urinary tract abnormalities may contribute to UTI by several mechanisms, including inadequate urine flow, incomplete emptying of the bladder, and incompetent anatomic junctions that permit reflux of contaminated urine. Differences between males and females in voiding pressures and residual urine volumes explain, in part, why boys tend to get more UTIs in the first months of life (initially lower voiding pressures). With maturation, girls have more UTIs after the first months of life. (See "Urinary tract infections in children: Epidemiology and risk factors", section on 'Host factors'.)

•Preterm infants – The prevalence of kidney and urinary tract abnormalities would be expected to be lower in preterm infants with UTI because many UTIs in this population are hospital acquired (ie, associated with urinary catheters and other invasive devices). However, data from retrospective studies suggest a similar rate of kidney and urinary tract abnormalities in preterm infants compared with term infants [10,17,18]. Among preterm infants with UTI hospitalized in a neonatal intensive care unit, abnormalities were seen on ultrasound in 35 to 40 percent [10,18]. The most common findings were pelviectasis and mild hydronephrosis. Major findings were seen in approximately 5 percent of patients and included high-grade hydronephrosis/VUR, kidney dysplasia, unilateral agenesis, partial duplication of the collecting system, and horseshoe kidney.

CLINICAL FEATURES — 

Clinical signs of UTI in neonates are nonspecific and are generally indistinguishable from signs of sepsis. (See "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at or after 35 weeks gestation", section on 'Clinical manifestations'.)

Infants with UTI can have lethargy, irritability, tachypnea, or cyanosis and may appear acutely ill.

Common clinical findings include [9,19-22]:

●Fever

●Lethargy

●Poor feeding

●Vomiting

●Apnea (most common in preterm neonates)

●Jaundice

●Loose stools (3 to 5 percent)

The hyperbilirubinemia that occurs with UTI typically is conjugated and related to cholestasis. Jaundice may be the first sign of UTI in some infants. In one report, UTI was diagnosed in 12 (7.5 percent) of 160 asymptomatic jaundiced infants less than eight weeks of age who presented to an emergency department [23]. In this cohort, infants with the onset of jaundice after eight days of age or patients with an elevated conjugated bilirubin fraction were more likely to have a UTI. (See "Approach to evaluation of cholestasis in neonates and young infants".)

Other less common findings include abdominal distension resulting from ileus or enlarged kidneys caused by hydronephrosis.

UTI may be the presenting manifestation that identifies a neonate with an underlying congenital anomaly of the kidney and urinary tract. (See 'Host factors' above.)

DIAGNOSIS — 

The following sections review tests used specifically to evaluate for UTI. However, testing for UTI in neonates is generally performed as part of a broader evaluation that includes other tests (eg, blood culture, lumbar puncture). The approach is discussed separately:

●Neonates undergoing sepsis evaluation during the birth hospitalization (see "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at or after 35 weeks gestation", section on 'Late-onset presentation' and "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at less than 35 weeks gestation", section on 'Late-onset (≥72 hours)')

●Febrile infants undergoing evaluation in the emergency department or outpatient setting (see "The febrile neonate (28 days of age or younger): Outpatient evaluation", section on 'Ancillary studies')

Urinalysis — Urinalysis includes both:

●Dipstick analysis, which includes testing for leukocyte esterase (a marker for pyuria) and nitrite (a marker for Enterobacteriaceae)

●Microscopic assessment of an unspun urine sample

For both tests, the urine should be obtained by either catheterization or suprapubic aspiration (SPA).

The test characteristics for dipstick and microscopic urinalysis in young infants are summarized in the table (table 1) [4,24].

In our practice, we generally perform urinalysis in conjunction with a urine culture to confirm or exclude the diagnosis of UTI in neonates [25,26]. However, for well-appearing febrile infants, some experts suggest performing urinalysis as the initial test and only perform culture if the urinalysis is positive (ie, reflexive testing) [27]. (See "The febrile neonate (28 days of age or younger): Outpatient evaluation", section on 'Well-appearing'.)

The advantage of performing both tests up front is that it has greater likelihood of identifying all affected neonates (ie, fewer false negatives). In addition, culture results and susceptibility testing may be available earlier, allowing for appropriate tailoring of antibiotic therapy. The advantage of sequential reflexive testing is that it reduces the likelihood of false positives.

As noted below, the presence of pyuria (either by either microscopic examination or positive leukocyte esterase) can be used to support a diagnosis of UTI when the colony count of a catheterized specimen falls between 10,000 and 50,000 colony-forming units (CFU)/mL. (See 'Urine culture' below.)

Additional details regarding urinalysis are provided separately. (See "Urinary tract infections in infants older than one month and children younger than two years: Clinical features and diagnosis", section on 'Rapidly available tests'.)

Urine culture — Diagnosis of UTI is based upon a positive urine culture from a specimen of urine that is either collected by bladder catheterization or SPA.

●Specimen collection – When performing urine culture in neonates, the specimen should be collected by bladder catheterization or SPA. "Clean voided" bag urine samples should not be used for culture, as there is a high rate of false-positive results. Despite efforts to improve the ability to obtain a midstream clean catch specimen in neonates [28,29], it remains an impractical and unreliable technique as there remains a high rate of contamination. (See "Urine collection techniques in infants and children with suspected urinary tract infection".)

Urine specimens should be transported on ice and must be processed expeditiously to avoid further growth of organisms in the urine specimen. If the specimen cannot be processed quickly, it should be refrigerated.

●Definitions of positive culture – A positive result is based on identifying a uropathogenic bacteria and reaching a threshold of number of CFU that grow on the culture medium. The number of CFU defining a positive urine culture varies based on the method of collection [25]:

•Bladder catheterization – For samples obtained via bladder catheterization, UTI is generally defined as growth of a single uropathogenic pathogen with a colony count of ≥50,000 CFU/mL or a colony count between 10,000 and 50,000 CFU/mL with associated pyuria detected on urinalysis [4,25,30,31]. However, the optimal definition for UTI based on a catheterized specimen in neonates has not been established [4]. (See 'Urinalysis' above.)

Bladder catheterization is a reliable method for detection of UTI in neonates. Specimen contamination is more likely with bladder catheterization than with SPA; however, this can be mitigated by discarding the initial stream and culturing the subsequent urine stream during catheterization. Many practitioners and parents also prefer bladder catheterization because they view SPA as much more invasive and painful. The technique is described in detail separately. (See "Urine collection techniques in infants and children with suspected urinary tract infection", section on 'Transurethral bladder catheterization'.)

•SPA – Any growth of a urinary pathogen is significant. The growth of one colony is equivalent to 1000 CFU/mL. SPA of the bladder urine is the most reliable technique to identify bacteriuria; however, it is rarely necessary [32]. The technique is described in detail separately. (See "Urine collection techniques in infants and children with suspected urinary tract infection", section on 'Suprapubic aspiration'.)

DIFFERENTIAL DIAGNOSIS — 

The signs and symptoms of neonatal UTI are nonspecific and generally indistinguishable from those of neonatal sepsis, as discussed above. (See 'Clinical features' above.).

Cultures of urine and other body fluids (eg, blood, cerebrospinal fluid) distinguish UTI from infection of the bloodstream or other site (eg, meningitis). In neonates, bacteremia frequently occurs concomitantly with UTI. (See "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at or after 35 weeks gestation", section on 'Diagnosis' and "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at less than 35 weeks gestation", section on 'Establishing the diagnosis'.)

The differential diagnosis of neonatal sepsis is broad, as summarized in the table (table 2) and discussed in detail separately. (See "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at or after 35 weeks gestation", section on 'Differential diagnosis'.)

FURTHER EVALUATION

Sepsis evaluation — If not performed during the initial evaluation, a sepsis evaluation should be performed in any neonate with suspected or confirmed UTI (ie, evidence of pyuria on urinalysis or positive urine culture).

●Blood culture – A blood culture should be obtained in all neonates with suspected or confirmed UTI. The risk of concurrent bacteremia in neonates with UTI varies from 4 to 7 percent in term infants [4,7]. In preterm infants, the risk of bacteremia may be as high as 10 to 14 percent [12]. Risk factors for bacteremia include gestational age <26 weeks and need for mechanical ventilation.

A positive blood culture does not alter initial management in most patients, because usually the same organism is isolated from the blood and urine, but it may alter the duration of therapy. (See "Neonatal bacterial sepsis: Treatment, prevention, and outcome in neonates born at less than 35 weeks gestation", section on 'Antibiotic therapy' and "Neonatal bacterial sepsis: Treatment, prevention, and outcome in neonates born at or after 35 weeks gestation".)

●Lumbar puncture – Clinicians should have a low threshold to perform a lumbar puncture as approximately 1 to 3 percent of infants with UTI have bacterial meningitis [12,33-35]. In particular, lumbar puncture should be performed in ill-appearing infants or those with neurologic findings (irritability, bulging fontanel) [36]. (See "Bacterial meningitis in the neonate: Clinical features and diagnosis".)

Radiographic evaluation

Approach to testing — Because of the high prevalence of urinary tract abnormalities, we perform radiographic evaluation in all neonates with UTI [4].

●Initial study (ultrasound for all patients) – The first step of the evaluation is ultrasonography of the kidneys and bladder to identify structural abnormalities. (See 'Ultrasonography' below.)

●Subsequent imaging (VCUG in selected patients) – We suggest voiding cystourethrogram (VCUG) to evaluate for vesicoureteral reflux (VUR) in neonates with any of the following:

•Abnormal kidney ultrasound

•Non-E. coli pathogen

•Recurrent UTI.

Ultrasonography — An ultrasound of the kidneys and bladder should be obtained after antibiotic treatment is initiated and the infant's clinical condition has stabilized. If prenatal ultrasonography (performed at a reputable center) was normal and the study results are accessible, postnatal ultrasonography may not be necessary. Many pregnant individuals have prenatal ultrasonography after 30 to 32 weeks of gestation, at which time, the urinary tract is fully developed. (See "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Antenatal screening'.)

Ultrasonography evaluates the size and position of the kidneys and the appearance of the collecting system, including the size and thickness of the bladder. Ultrasound can detect dilation of the collecting system, structural abnormalities (eg, solitary kidney, multicystic dysplasia, duplex collecting system), and echogenic fungal material or stones. As noted above, approximately 30 to 50 percent of neonates with UTI have abnormalities on kidney ultrasound, most commonly pelviectasis or mild hydronephrosis. However, a normal ultrasound examination does not exclude VUR or kidney scarring [16]. (See 'Host factors' above and "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)".)

Voiding cystourethrogram — A VCUG should be performed in neonates with abnormal ultrasound findings. Expert opinion differs as to whether VCUG is necessary in neonates with UTI who have no abnormalities detected by ultrasound. Our practice for most neonates with first-time UTI and normal kidney ultrasound is to "wait and watch." At the author's institution, VCUGs are generally performed only in neonates with abnormal kidney ultrasound, non-E. coli pathogen, or recurrent UTI. Other centers routinely perform VCUGs in all neonates with first-time febrile UTI.

The prevalence of clinically significant VUR appears to be very low among infants with normal kidney ultrasound and E. coli infection. In a retrospective study that included 122 infants (<3 months old) with first febrile UTI, those with normal kidney ultrasound and E. coli infection were less likely to have high-grade VUR compared with those with abnormal kidney ultrasound, non-E. coli pathogen, or both abnormal ultrasound and non-E. coli pathogen (1 versus 31, 26, and 55 percent, respectively) [37]. Limitations of this study include the small sample size and lack of long-term follow-up.

If a "wait and watch" approach is used, patients should be monitored for recurrence (eg, if the infant has a febrile illness, a urine sample should be obtained to evaluate for UTI). If the patient develops a subsequent UTI, evaluation with VCUG is appropriate. (See "Urinary tract infections in infants older than one month and children younger than two years: Acute management, imaging, and prognosis", section on 'Voiding cystourethrogram'.)

Other imaging — Radionuclide imaging may be used to identify scarring and acute changes due to pyelonephritis. It is not generally helpful in the acute setting but may be obtained as part of follow-up evaluation, particularly if kidney damage is suggested by ultrasonography. Although computed tomography also can identify these findings, it is not suggested for routine use, because of the exposure to radiation. (See "Urinary tract infections in infants older than one month and children younger than two years: Acute management, imaging, and prognosis", section on 'Renal scintigraphy'.)

TREATMENT — 

Treatment with intravenous (IV) broad-spectrum antimicrobial agents should be initiated as soon as cultures of urine, blood, and cerebrospinal fluid (if indicated) have been obtained. The effectiveness of antimicrobial therapy for pediatric UTIs is demonstrated by in the dramatic reduction in morbidity and mortality between the pre- and post-antibiotic eras. The mortality of infantile UTI was as high as 20 percent in the pre-antibiotic era. In contrast, when UTIs are appropriately treated with antibiotics, acute complications (eg, abscess, kidney injury, death) are uncommon.

Antibiotic therapy — Antibiotic therapy includes initial parenteral empiric antibiotic therapy pending culture results, as well as organism-specific therapy based on the isolated organism and its antibiotic susceptibility.

Empiric therapy — For most neonates with UTI, we suggest initial empiric coverage with ampicillin plus an aminoglycoside (typically gentamicin). However, local antibiotic susceptibility patterns should be considered when determining appropriate initial antibiotic therapy. For hospital-acquired infections, vancomycin is substituted for ampicillin since the predominant organisms include coagulase-negative staphylococci, S. aureus, and Enterococcus species. (See 'Microbiology' above.)

The empiric regimen for UTI is the same regimen as is used for empiric treatment of neonatal sepsis more broadly. The same regimen is used because the causative agents are similar in neonatal sepsis and UTI, it is difficult to differentiate between the two based on presentation, and there is risk of concurrent bloodstream infection in neonates with UTI. Empiric therapy for neonatal sepsis is summarized in the table (table 3) and discussed in greater detail separately. (See "Neonatal bacterial sepsis: Treatment, prevention, and outcome in neonates born at or after 35 weeks gestation", section on 'Initial empiric therapy' and "Neonatal bacterial sepsis: Treatment, prevention, and outcome in neonates born at less than 35 weeks gestation", section on 'Empiric antibiotic therapy'.)

Organism-specific therapy — Once culture results are available, antimicrobial therapy is altered based upon the isolated pathogen, its antimicrobial susceptibility pattern, and whether other sites are also infected (eg, bacteremia or meningitis). (See "Neonatal bacterial sepsis: Treatment, prevention, and outcome in neonates born at or after 35 weeks gestation" and "Neonatal bacterial sepsis: Treatment, prevention, and outcome in neonates born at less than 35 weeks gestation", section on 'Organism-specific therapy'.)

Response to therapy — Sterilization of the urine should occur within 48 hours of treatment with the appropriate antimicrobial agent. It is not necessary to routinely obtain repeat urine cultures during antimicrobial therapy to document sterilization of the urine, provided that the uropathogen is susceptible to the selected antibiotic and the infant has a good clinical response. However, if the infant fails to respond clinically or if the uropathogen is not susceptible (intermediate or resistant) to the selected antibiotic, follow-up urine culture should be performed after 48 hours of therapy. If bacteriuria persists despite appropriate therapy, imaging should be performed and cultures or other sites obtained to investigate for a potential reservoir of infection.

Duration of therapy — The optimal duration of treatment for neonatal UTI is uncertain. In our center, the duration of antibiotic therapy is 10 to 14 days for neonates with uncomplicated bacterial UTI (ie, susceptible E. coli isolate in a patient with a normal kidney ultrasound). We usually complete the treatment course in neonates with a course of IV antibiotics, although older infants with uncomplicated UTIs can be switched to oral antibiotics after clinical improvement based on the judgement of the individual clinician.

Longer treatment may be needed for fungal infections. This is discussed separately. (See "Candida infections in neonates: Treatment and prevention", section on 'Treatment based on extent of disease'.)

PREVENTION OF RECURRENT EPISODES

Indications — After completing treatment for UTI, antibiotic prophylaxis to prevent recurrent episodes of UTI is appropriate in the following circumstances:

●For patients who have not yet completed the radiographic evaluation for urinary tract abnormalities by the end of treatment. In these patients, prophylactic therapy is provided until the radiographic evaluation is complete, with the need for ongoing prophylaxis determined by the imaging findings. (See 'Radiographic evaluation' above.)

●For patients in whom the radiographic evaluation identifies an abnormality that warrants prophylaxis. The role of antibiotic prophylaxis in specific congenital kidney and collecting system abnormalities is discussed in separate topic reviews:

•Hydronephrosis (see "Postnatal evaluation and management of hydronephrosis", section on 'Antibiotic prophylaxis')

•Ureteropelvic junction obstruction (see "Congenital ureteropelvic junction obstruction", section on 'Antibiotic prophylaxis')

•Vesicoureteral reflux (see "Management of vesicoureteral reflux", section on 'Antibiotic prophylaxis')

•Primary megaureter (see "Primary megaureter in infants and children", section on 'Medical management')

•Ectopic ureter or duplex collecting system (see "Ectopic ureter", section on 'Management')

Agent and dosing — When prophylaxis is indicated, it typically consists of amoxicillin given orally once daily at a dose of 10 to 15 mg/kg per day. Cephalexin (10 mg/kg orally once daily) is a reasonable alternative. (See "Management of vesicoureteral reflux", section on 'Agents and dosing'.)

OUTCOME — 

Infants who have had UTI during the neonatal period are at risk for developing kidney parenchymal scarring, reduced kidney growth, and impaired kidney function [8,38-40]. The risk is increased among patients with vesicoureteral reflux (VUR), especially if there are recurrent episodes of UTI. Kidney parenchymal scarring is associated with an increased risk for hypertension and chronic kidney disease. This is discussed in detail separately. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Loss of kidney parenchyma'.)

In one study that prospectively followed 648 patients diagnosed with UTI in early infancy, 19 percent had evidence of loss of kidney parenchyma and reduced kidney function on radionuclide imaging performed >6 months after the initial UTI; severely reduced kidney function was seen in 6 percent [8].

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" and "Society guideline links: Sepsis in neonates".)

SUMMARY AND RECOMMENDATIONS

●Prevalence and risk factors – The prevalence of urinary tract infection (UTI) among term neonates who present to the emergency department or outpatient clinic with fever is approximately 10 to 20 percent. Neonatal UTI can also occur as a complication associated with prematurity or other medical condition that prolongs the birth hospitalization. (See 'Epidemiology' above.)

●Risk factors – Factors associated with increased risk of UTI in neonates and young infants include (see 'Host factors' above):

•Male sex (especially if uncircumcised)

•Preterm birth

•Presence of invasive devices (especially urinary catheters)

•Congenital anomalies of the kidney and urinary tract.

●Common pathogens – In term neonates with community-acquired UTI, Escherichia coli is the most common organism, accounting for 80 to 90 percent of cases. In hospitalized neonates, E. coli remains and important pathogen, but other pathogens (eg, coagulase-negative Staphylococcus, Klebsiella, Candida) are also commonly seen. (See 'Microbiology' above.)

●Clinical features– Clinical signs of UTI in neonates are nonspecific and indistinguishable from signs of neonatal sepsis. They include fever, lethargy, poor feeding, vomiting, and conjugated hyperbilirubinemia. In addition, apnea and bradycardia can be seen in preterm infants. (See 'Clinical features' above.)

●Diagnosis – UTI is diagnosed based upon culture of an organism from a specimen obtained by bladder catheterization or suprapubic aspiration (SPA). "Clean voided" bag urine samples should not be used for culture. The threshold used to define a positive result depends upon the method used (see 'Urine culture' above):

•Catheterization samples – Growth of a single uropathogenic pathogen with a colony count of ≥50,000 colony-forming units (CFU)/mL or a colony count between 10,000 and 50,000 CFU/mL with associated pyuria detected on urinalysis

•SPA samples – Any growth of a urinary pathogen is considered positive (ie, >1000 CFU/mL)

●Other cultures – Because of the risk of concurrent bacteremia, blood cultures should be obtained in all neonates with suspected or confirmed UTI. In addition, clinicians should have a low threshold to perform a lumbar puncture, particularly if the infant is ill appearing or has neurologic findings (irritability, bulging fontanel). (See 'Sepsis evaluation' above and "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at or after 35 weeks gestation", section on 'Laboratory tests' and "The febrile neonate (28 days of age or younger): Outpatient evaluation", section on 'Ancillary studies'.)

●Treatment

•Empiric therapy – Treatment with intravenous (IV) broad-spectrum antimicrobial agents should be initiated as soon as cultures of urine, blood, and cerebrospinal fluid (if indicated) have been obtained. The empiric regimen for UTI is the same regimen as is used for empiric treatment of neonatal sepsis more broadly, as summarized in the table (table 3) and discussed separately. (See "Neonatal bacterial sepsis: Treatment, prevention, and outcome in neonates born at or after 35 weeks gestation", section on 'Initial empiric therapy'.)

•Definitive treatment – Once culture results are available, antibiotic therapy is adjusted based on antimicrobial susceptibilities. The usual duration of treatment for neonates with uncomplicated UTI (ie, susceptible E. coli isolate in a patient with a normal kidney ultrasound) is 10 to 14 days. We typically treat with intravenous (IV) therapy for the entire duration; others may switch from IV to oral antibiotics to complete the course of therapy in older infants after clinical improvement. (See 'Organism-specific therapy' above and 'Duration of therapy' above.)

●Radiologic evaluation – Because of the high prevalence of congenital urinary tract abnormalities in neonates with UTI, radiographic evaluation is performed in all neonates diagnosed with UTI. The first step is ultrasonography of the kidneys and bladder to identify structural abnormalities. In addition, for neonates with abnormal ultrasound findings, non-E. coli pathogen, or recurrent UTI, we suggest voiding cystourethrogram (VCUG) to evaluate for vesicoureteral reflux (VUR). (See 'Radiographic evaluation' above.)

●Outcome – Neonates with UTIs are at risk for developing kidney scarring, which is associated with hypertension and chronic kidney disease. (See 'Outcome' above.)