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Urinary tract infections in neonates

Urinary tract infections in neonates
Author:
Donough J O'Donovan, MD
Section Editors:
Tej K Mattoo, MD, DCH, FRCP
Morven S Edwards, MD
Leonard E Weisman, MD
Deputy Editor:
Laurie Wilkie, MD, MS
Literature review current through: Apr 2022. | This topic last updated: Mar 07, 2022.

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 renal 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 and children older than one month: Clinical features and diagnosis" and "Urinary tract infections in infants older than one month and young children: Acute management, imaging, and prognosis".)

EPIDEMIOLOGY

Febrile term infants — Among neonates and young infants presenting to the emergency department or outpatient clinic with fever, reported rates of UTI vary from approximately 10 to 20 percent [1-5]. In one retrospective study of 670 febrile infants less than 30 days of age who presented to a pediatric emergency department over a 10-year period from 2004 to 2013, 15 percent of patients (n = 100) had a positive urine culture of a specimen obtained by bladder catheterization [1]. Four patients had urosepsis, but there were no deaths or cases of bacterial meningitis.

UTI is uncommon in the first few days of life even in neonates with bacteremia. Thus, urine cultures are not routinely included in the evaluation for early-onset sepsis in term neonates, since UTI is identified in <1 percent of such patients [1,6]. This is discussed separately. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants", section on 'Urine culture'.)

Preterm infants — Although data are limited regarding the prevalence of UTI in preterm infants, it appears that the risk increases with decreasing gestational age and birth weight. In one study from an Israeli neonatal intensive care unit from 1990 to 1993, the reported prevalence was 8 percent, but extremely low birth weight infants (birth weight <1000 g) had a greater risk of 13 percent [7].

MICROBIOLOGY

Term infants — In term infants who present with community-acquired infection, Escherichia coli is the most common pathogen accounting for up to 80 percent of infections in most large series [1,2]. 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 — Coagulase-negative Staphylococcus and Klebsiella are more likely causes of UTI in hospitalized preterm infants, and E. coli is less commonly seen [7-9]. Candida species are also frequent urinary pathogens in preterm infants, particularly in extremely low birth weight infants (birth weight <1000 g) [7,10]. (See "Clinical manifestations and diagnosis of Candida infection in neonates", 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 sepsis 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 [1,13]. 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) [8]. (See "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Risk factors associated with prematurity' and 'Preterm infants' above.)

Kidney and urinary tract abnormalities – Renal or urologic 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 [1,2,13,15,16]. Major renal 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 [1,2,13,15,16]. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux".)

In a case series of 95 term neonates with UTI who underwent renal ultrasound imaging, 45 had a renal anatomic abnormality including 19 with pelviectasis and 26 with hydronephrosis (graded as mild in 12 cases and moderate in 14 cases) [1]. 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 "Congenital ureteropelvic junction obstruction", section on 'Infants' and "Clinical presentation and diagnosis of posterior urethral valves", section on 'Postnatal')

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

-Renal parenchymal disorders (eg, polycystic diseases, renal 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 renal or urologic 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 renal or urinary tract abnormalities in preterm infants compared with term infants [9,17,18]. Among preterm infants with UTI hospitalized in a neonatal intensive care unit, abnormalities were seen on ultrasound in 35 to 40 percent [9,18]. 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, renal dysplasia, unilateral agenesis, partial duplication of the collecting system, and horseshoe kidney.

CLINICAL FEATURES

Term infants — The signs and symptoms of UTI in neonates are nonspecific. Infants can have lethargy, irritability, tachypnea, or cyanosis and may appear acutely ill.

The most common clinical findings are [19-22]:

Fever (20 to 40 percent)

Poor weight gain (15 to 43 percent)

Jaundice (3 to 41 percent)

Vomiting (9 to 41 percent)

Loose stools (3 to 5 percent)

Poor feeding (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 (CAKUT). (See 'Host factors' above.)

Preterm infants — The clinical manifestations of UTI in preterm infants are similar to those of term infants, with the addition of apnea and hypoxia. In a study of 56 preterm infants with UTI born between 1995 and 2003, the following findings were noted [8].

Feeding intolerance (62 percent)

Apnea and bradycardia (45 percent)

Lethargy (30 percent)

Tachypnea (30 percent)

Abdominal distension (12 percent)

Hypoxia with documented oxygen desaturation (12 percent)

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) (see 'Sepsis evaluation' below). The approach is discussed separately. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants", section on 'Laboratory tests' and "The febrile neonate (28 days of age or younger): Outpatient evaluation and initial management", section on 'Evaluation'.)

Urinalysis — Urinalysis includes both:

Dipstick analysis, which includes testing for leukocyte esterase (marker for pyuria) and nitrite (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) [1,3,24,25].

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

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 [1,26,30,31]. However, the optimal definition for UTI based on a catheterized specimen in neonates has not been established [1]. (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 — Because the signs and symptoms of neonatal UTI are nonspecific (see 'Clinical features' above), several other disorders may present with similar findings:

Other infectious conditions including sepsis and meningitis – Cultures of urine and other body fluids (eg, blood, cerebrospinal fluid) distinguish UTI from these other infectious diseases. UTI can occur concomitantly with these other infectious conditions. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants", section on 'Diagnosis' and "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Diagnosis'.)

Inborn errors of metabolism. (See "Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features", section on 'Clinical manifestations'.)

FURTHER EVALUATION

Sepsis evaluation — 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 [1,2]. 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 the vast majority of patients, because usually the same organism is isolated from the blood and urine, but it may alter the duration of therapy. (See "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Antibiotic therapy' and "Management and outcome of sepsis in term and late preterm infants".)

In addition, 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 — Because of the high prevalence of urinary tract abnormalities, we perform radiographic evaluation in all neonates with UTI [1]. The first step of this evaluation is renal ultrasonography to identify structural abnormalities. In addition, we suggest voiding cystourethrogram (VCUG) to evaluate for vesicoureteral reflux (VUR) in neonates with abnormal renal ultrasound, non-E. coli pathogen, or recurrent UTI.

Renal ultrasonography — A renal ultrasound 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 renal ultrasonography may not be necessary. Many pregnant women 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'.)

Renal 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 renal ultrasound, most commonly pelviectasis or mild hydronephrosis. However, a normal ultrasound examination does not exclude VUR or renal 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 renal ultrasound is to "wait and watch." At the author's institution, VCUGs are generally performed only in neonates with abnormal renal 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 renal ultrasound and E. coli infection. In a retrospective study that included 122 infants (<3 months old) with first febrile UTI, those with normal renal ultrasound and E. coli infection were less likely to have high-grade VUR compared with those with abnormal renal 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 young children: Acute management, imaging, and prognosis", section on 'Voiding cystourethrogram'.)

Other imaging — Renal cortical scintigraphy (with Tc99m-dimercaptocuccinic acid [DMSA]) may be used to identify renal 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 renal 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 young children: 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 the change in mortality between the pre- and post-antibiotic eras. The mortality of UTI was as high as 20 percent in the pre-antibiotic era. In contrast, when UTIs are appropriately treated with antibiotics, acute complications (eg, renal abscess, death) are uncommon. (See "Urinary tract infections in infants older than one month and young children: Acute management, imaging, and prognosis", section on 'Antibiotic therapy'.)

Choice of agent and dosing — 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 — The choice and dosing of empiric antibiotic therapy is generally the same as for the treatment of neonatal sepsis. This is 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 infection. (See "Management and outcome of sepsis in term and late preterm infants", section on 'Initial empiric therapy' and "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Empiric antibiotic therapy'.)

The combination of parenteral ampicillin and gentamicin provides coverage for the most common bacterial pathogens. However, with increasing reports of resistant organisms, local surveillance of pathogens and antibiotic susceptibility patterns may be important to determine appropriate initial antibiotic therapy [38].

Recommendations for ampicillin and gentamicin dosing in neonates vary [39,40]. Doses are dependent on the weight and chronologic age of the infant [39]:

Gestational age >34 weeks:

Ampicillin – For neonates ≤7 days old, the dose is 50 mg/kg per dose IV every 8 hours; for neonates >7 days old, the dose is 50 mg/kg per dose IV every 6 hours.

Gentamicin – For neonates ≤7 days old, the dose is 4 mg/kg per dose IV every 24 hours; for neonates >7 days old, the dose is 5 mg/kg per dose IV every 24 hours.

Gestational age ≤34 weeks:

Ampicillin – For neonates ≤7 days old, the dose is 50 mg/kg per dose IV every 12 hours; for neonates >7 days old with community-acquired UTI, the dose is 50 mg/kg per dose IV every 8 hours. However, most late UTIs in low birth weight neonates are hospital acquired and vancomycin is suggested rather than ampicillin in this setting, as discussed below.

Gentamicin – For neonates 30 to 34 weeks gestation who are ≤14 days old, the dose is 5 mg/kg per dose IV every 36 hours; for neonates >14 days old, the dose is 5 mg/kg per dose IV every 24 hours. For neonates <30 weeks gestation who are ≤14 days old, the dose is 5 mg/kg per dose IV every 48 hours; for neonates >14 days old, the dose is 5 mg/kg per dose IV every 36 hours.

The choice of empiric regimen also depends on the clinical setting:

For hospital-acquired infections, vancomycin is substituted for ampicillin since the predominant organisms include coagulase-negative staphylococci, S. aureus, and Enterococcus species. (See 'Preterm infants' above.)

If meningitis is also suspected, higher doses of antibiotics must be used. In infants >7 days old, a third-generation cephalosporin (eg, cefotaxime, if available) is added, pending culture results [39]. This is discussed in a separate topic review. (See "Bacterial meningitis in the neonate: Treatment and outcome", section on 'Empiric therapy'.)

Organism-specific therapy — Antimicrobial therapy is altered based upon the isolation of a pathogen, its pattern of antimicrobial susceptibility, and if there are concurrent infections (eg, sepsis or meningitis). (See "Management and outcome of sepsis in term and late preterm infants", section on 'Culture-proven sepsis' and "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Organism-specific therapy' and "Bacterial meningitis in the neonate: Treatment and outcome", section on 'Definitive therapy'.)

Response to therapy — Sterilization of the urine should occur within 48 hours of treatment with the appropriate antimicrobial agent. Optimally, it should be confirmed by repeating the urine culture at that time. If bacteriuria persists despite appropriate therapy, the urinary tract and other sites should be investigated to determine 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 renal 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 is often needed for fungal infections. (See "Treatment of Candida infection in neonates", section on 'Urinary tract infection'.)

In our center, antibiotic prophylaxis with low-dose, orally administered amoxicillin (15 to 20 mg/kg per day) is started until radiographic evaluation has been performed to evaluate for urinary tract abnormalities. Continuation of this prophylaxis depends upon the results of imaging studies. (See 'Radiographic evaluation' above.)

OUTCOME — Infants who have had UTI during the neonatal period are at risk for developing renal parenchymal scarring [41,42]. The risk is increased among patients with vesicoureteral reflux (VUR). Renal 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 renal parenchyma'.)

Neonatal UTI may impair renal growth. In one study, 22 children who had UTI before reaching one month of age were followed for 12 to 21 years [43]. Renal growth was decreased in patients with and without reflux at approximately four years after the UTI, although renal size tended to become normal later.

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) is approximately 10 to 20 percent among term neonates who present with fever. UTI is uncommon in the first few days after birth. The incidence is higher in uncircumcised males, and the risk appears to increase with decreasing gestational age in preterm infants. In addition, congenital anomalies of the kidney and urinary tract (CAKUT) are important predisposing factors for neonatal UTI. (See 'Epidemiology' above and 'Host factors' above.)

Common pathogens – In term neonates with community-acquired UTI, Escherichia coli is the most common organism, accounting for up to 80 percent of UTIs. In hospitalized neonates, especially preterm infants, coagulase-negative Staphylococcus and Klebsiella are more likely causes of UTI and E. Coli is less commonly seen. (See 'Microbiology' above.)

Signs and symptoms – The signs and symptoms of neonatal UTIs are numerous and nonspecific. They include fever, failure to thrive, conjugated hyperbilirubinemia, and vomiting. In addition, apnea and hypoxia are also seen in preterm infants. (See 'Clinical features' above.)

Diagnosis – Diagnosis of neonatal UTI is 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 "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants", section on 'Laboratory tests' and "The febrile neonate (28 days of age or younger): Outpatient evaluation and initial management", section on 'Ancillary studies'.)

Treatment – Treatment consists of initial parenteral empiric antibiotic therapy pending culture results, as well as organism-specific therapy based on the isolated organism and its antibiotic susceptibility. (See 'Treatment' above.)

Empiric therapy – Empiric therapy is appropriate if initial testing suggests UTI (eg, positive leukocyte esterase or pyuria on microscopic urinalysis) and/or if there are concerning clinical findings (eg, fever, ill appearance). Treatment should be initiated as soon as cultures of urine, blood, and cerebrospinal fluid (if indicated) have been obtained and should provide broad coverage for the most likely pathogens. For most neonates, we suggest ampicillin and gentamicin for empiric therapy rather than other regimens (Grade 2C). However, alternative regimens may be preferred based on local surveillance of pathogens and antibiotic susceptibility patterns. (See 'Empiric therapy' above.)

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 renal 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 CAKUT, radiographic evaluation is performed in all neonates with UTI. The first step is renal ultrasonography to identify structural abnormalities. In addition, for neonates with abnormal renal ultrasound, 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 upper tract UTIs are at risk for developing renal scarring, which is associated with hypertension and chronic kidney disease. (See 'Outcome' above.)

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