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Urinary tract infections in children: Epidemiology and risk factors

Urinary tract infections in children: Epidemiology and risk factors
Authors:
Nader Shaikh, MD
Alejandro Hoberman, MD
Section Editors:
Morven S Edwards, MD
Tej K Mattoo, MD, DCH, FRCP
Deputy Editor:
Mary M Torchia, MD
Literature review current through: Dec 2022. | This topic last updated: Dec 02, 2022.

INTRODUCTION — Urinary tract infection (UTI) is a common and important clinical problem in childhood. Upper UTIs (ie, acute pyelonephritis) may lead to renal scarring, hypertension, and end-stage kidney disease. Although children with pyelonephritis tend to present with fever, it is often 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 presence of risk factors for UTI and renal scarring in a child presenting with fever and/or urinary symptoms is helpful in guiding diagnostic testing and management. The epidemiology and risk factors for UTI and renal scarring in children will be reviewed here. Clinical features, diagnosis, and management of UTI, and UTI in newborns (younger than one month of age) 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" and "Urinary tract infections in children: Long-term management and prevention" and "Urinary tract infections in neonates".)

EPIDEMIOLOGY

Prevalence — Awareness of the prevalence of UTI in various subgroups of children enables the clinician to grossly estimate the probability of infection in the patient (ie, the pretest probability) (table 1). This information is important in the evaluation of a child with suspected UTI. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Decision to obtain urine sample'.)

In young children with fever — The prevalence of UTI in children <2 years presenting with fever has been the subject of several large prospective studies and a meta-analysis (table 1) [2-4]. Important points that emerged from these studies include:

The overall prevalence of UTI is approximately 7 percent in febrile infants and young children but varies by age, sex, and circumcision status.

The prevalence is highest among uncircumcised males, particularly those who are younger than three months.

Females have a two- to fourfold higher prevalence of UTI than do circumcised males.

For children age 2 through 23 months of age, the probability of UTI can be estimated on a case-by-case basis using an online calculator from the University of Pittsburgh (UTICalc) [5,6].

In older children — In pooled analysis of four studies that included children <19 years (most of whom were older than two years) and had urinary symptoms and/or fever, the prevalence of UTI was 7.8 percent (95% CI 6.6-8.9) [4].

MICROBIOLOGY — Escherichia coli is the most common bacterial cause of UTI; it accounts for approximately 80 percent of UTI in children [7]. Other gram-negative bacterial pathogens include Klebsiella, Proteus, Enterobacter, and Citrobacter. Gram-positive bacterial pathogens include Staphylococcus saprophyticus, Enterococcus, and, rarely, Staphylococcus aureus.

Infection with an organism other than E. coli is associated with a higher likelihood of renal scarring. In a meta-analysis of individual patient data from nine studies including 1280 children (0 to 18 years) who underwent renal scintigraphy at least five months after their first UTI, non-E. coli UTI was associated with an increased risk of renal scarring (odds ratio 2.2, 95% CI 1.3-3.6) [8].

The inflammatory response, as measured by the white cell count, appears to differ according to the pathogen. In a retrospective review of 1181 children diagnosed with UTI, children with Enterococcus species, Klebsiella species, and Pseudomonas aeruginosa were less likely to have pyuria than children with Escherichia coli (odds ratio of 0.14, 0.34, and 0.19, respectively) [9].

Viruses (eg, adenovirus, enteroviruses, Coxsackieviruses, echoviruses) and fungi (eg, Candida spp, Aspergillus spp, Cryptococcus neoformans, endemic mycoses) are uncommon causes of UTI in children [10,11]. Viral UTI are usually limited to the lower urinary tract. Risk factors for fungal UTI include immunosuppression and long-term use of broad-spectrum antibiotic therapy, and indwelling urinary catheter [12]. (See "Acute infectious cystitis: Clinical features and diagnosis in children older than two years and adolescents", section on 'Microbiology'.)

PATHOGENESIS — The bacteriology of UTI, along with the observation that a minority (4 to 9 percent) of children with UTI are bacteremic [13,14], is consistent with the hypothesis that most UTI beyond the newborn period are the result of ascending infection.

Colonization of the periurethral area by uropathogenic enteric pathogens is the first step in the development of a UTI. The presence of pathogens on the periurethral mucosa, however, is not sufficient to cause UTI [15]. Pathogens attach to the uroepithelial cells via an active process mediated by glycosphingolipid receptors on the surface of epithelial cells [16-18]. Bacterial attachment recruits toll-like receptors (TLR), a family of transmembrane coreceptors involved in the recognition of pathogen-associated protein patterns [18]. TLR binding triggers a cytokine response, which generates a local inflammatory response.

A variety of virulence factors enable bacteria to ascend into the bladder and kidney. The best-studied virulence factors in E. coli are pili, hair-like appendages on the cell surface. Bacteria possessing pili can adhere effectively to the uroepithelium and ascend into the kidney, even in children without vesicoureteral reflux. In the kidney, the bacterial inoculum generates an intense inflammatory response, which may ultimately lead to renal scarring. (See "Bacterial adherence and other virulence factors for urinary tract infection".)

HOST FACTORS — A variety of host factors influence the predisposition to UTI in children.

Age — The prevalence of UTI is highest in males younger than one year and females younger than four years [4,19].

Lack of circumcision — Uncircumcised male infants with fever have a four- to eightfold higher prevalence of UTI than circumcised male infants [4,20]. (See 'Prevalence' above.)

Two plausible mechanisms have been proposed to explain this difference:

The mucosal surface of the uncircumcised foreskin is more likely to bind uropathogenic bacterial species than keratinized skin on a circumcised penis [21]. The keratinization of the mucosa is largely complete by one year of age and temporally coincides with the decreasing prevalence of UTI in males.

Partial obstruction of the urethral meatus by a tight foreskin may be the explanation for the higher incidence of UTI in uncircumcised males [22,23]. In one study of uncircumcised male infants (<7 months of age), inability to retract the foreskin to expose the urethral meatus was more common among males with febrile UTI than among those without UTI (85 versus 42 percent) [22]. The tightness of the foreskin diminishes with time and is an infrequent finding after one year of age [22].

Despite the increased risk, most uncircumcised males do not develop UTI [24]. A systematic review of randomized and observational studies of circumcision for the prevention of UTI found that 111 circumcisions would be needed to prevent one UTI [20]. Sensitivity analysis of a decision model for circumcision suggested that the decision to circumcise a child hinges more heavily on the caregivers' values regarding pain than on the UTI prevalence or circumcision complication rates [25]. This observation underscores the importance of respecting caregiver values as they decide whether to circumcise their sons. (See "Neonatal circumcision: Risks and benefits".)

Female infants — Female infants have a two- to fourfold higher prevalence of UTI than male infants [4]. This has been presumed to be the result of the shorter female urethra. However, because the incidence of UTI in male neonates is as high, if not higher, than in female neonates, the importance of the length of the urethra in the pathogenesis of UTI has been questioned. Alternatively, the propensity of bacterial attachment to the female periurethral mucosa may account for this difference.

Genetic factors — First-degree relatives of children with UTI are more likely to have UTI than individuals without such a history [26,27]. Adherence of bacteria may, in part, be genetically determined. As an example, uroepithelial cells of females who are nonsecretors of blood group antigens have enhanced adherence of uropathogenic E. coli [28,29]. Genetic factors also may affect the density of E. coli receptors in the periurethral area and the ability to mount an inflammatory response [30,31]. (See "Bacterial adherence and other virulence factors for urinary tract infection" and "Recurrent simple cystitis in women", section on 'Risk factors'.)

Urinary obstruction — Children with obstructive urologic abnormalities are at increased risk of developing UTI; stagnant urine is an excellent culture medium for most uropathogens. Predisposing obstructive abnormalities include the following:

Anatomic conditions (eg, posterior urethral valves, ureteropelvic junction obstruction) (see "Clinical presentation and diagnosis of posterior urethral valves" and "Congenital ureteropelvic junction obstruction")

Neurologic conditions (eg, myelomeningocele with neurogenic bladder) (see "Myelomeningocele (spina bifida): Urinary tract complications")

Functional conditions (eg, bladder and bowel dysfunction) (see "Etiology and clinical features of bladder dysfunction in children" and "Evaluation and diagnosis of bladder dysfunction in children" and "Functional constipation in infants, children, and adolescents: Clinical features and diagnosis")

Despite the increased risk of UTI in children with obstructive abnormalities, obstructive anatomic abnormalities are infrequent in children presenting with a first UTI (1 to 4 percent) [1,32-35]. Urinary obstruction should be suspected when the patient has voiding problems (eg, daytime enuresis, dribbling of urine), when other family members have had urologic abnormalities, when genitourinary abnormalities are detected on physical examination, or when symptoms do not respond to appropriate therapy.

Bladder and bowel dysfunction — Bladder and bowel dysfunction, of which bladder dysfunction is a subset, is characterized by [36]:

An abnormal elimination pattern (frequent or infrequent voids, daytime wetting, urgency, infrequent stools [constipation])

Bladder and/or bowel incontinence

Withholding maneuvers

Bladder and bowel dysfunction usually presents in otherwise-healthy school-age children and may persist for months to years. The pathophysiology is varied but basically involves a behavioral abnormality of function of the muscles of the pelvis, bladder, and/or sphincter. Although this condition is relatively common in children, it is often underdiagnosed and undertreated by primary care clinicians [37,38]. Presenting manifestations include daytime wetting, withholding behaviors, and constipation [36].

Bladder and bowel dysfunction is an important and often overlooked factor in the pathophysiology of UTI in children [37,38]. Up to 40 percent of toilet-trained children with their first UTI and 80 percent of children with recurrent (three or more) UTI report symptoms of bladder and bowel dysfunction [32,39-42]. Bladder and bowel dysfunction is also a risk factor for persistent vesicoureteral reflux (VUR), renal scarring [39,40,43-45], and recurrent UTIs [46,47]. At baseline, bladder and bowel dysfunction was identified in 56 percent of 126 toilet-trained children (<6 years of age) enrolled in the randomized intervention for VUR (RIVUR) trial comparing antibiotic prophylaxis and placebo in children with grades I to IV VUR and in 46 percent of 57 toilet-trained children without VUR observed in the Careful Urinary Tract Infection Evaluation (CUTIE) study [47,48]. In both studies, bowel and bladder dysfunction was associated with increased risk of recurrent UTIs (hazard ratio 2.07, 95% CI 1.09-3.93) [47]. (See "Etiology and clinical features of bladder dysfunction in children".)

The clinical features and diagnosis of bowel and bladder dysfunction are discussed separately. (See "Constipation in infants and children: Evaluation" and "Etiology and clinical features of bladder dysfunction in children" and "Evaluation and diagnosis of bladder dysfunction in children".)

Vesicoureteral reflux — VUR is the retrograde passage of urine from the bladder into the upper urinary tract. It is the most common urologic anomaly in children. Children with VUR are at increased risk for recurrent UTI. The clinical manifestations, management, and long-term implications of VUR are discussed separately. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux" and "Management of vesicoureteral reflux".)

Sexual activity — The association between sexual intercourse and UTI in females has been well documented. (See "Acute simple cystitis in females", section on 'Epidemiology'.)

Bladder catheterization — The risk of UTI increases with increasing duration of bladder catheterization. (See "Catheter-associated urinary tract infection in adults".)

BACTERIAL-HOST INTERACTIONS — There is indirect evidence that alteration of the normal periurethral flora promotes attachment of pathogenic bacteria as illustrated by the following observations (see 'Pathogenesis' above):

In one study, E. coli and other gram-negative uropathogenic organisms were cultured more frequently from the urethras of uncircumcised males than from those of circumcised males [49].

In a prospective study of preschool children with bacteriuria, recent treatment with antibiotics for upper respiratory infections was associated with an increased risk of febrile UTI [26].

The use of spermicidal condoms and spermicidal jelly with diaphragms has been independently associated with E. coli bacteriuria, suggesting that these agents predispose to UTI by altering the normal vaginal flora (Lactobacillus and Corynebacterium spp) [50].

In experimental studies in monkeys, the use of beta-lactam antibiotics (eg, penicillins and cephalosporins) disturbed the normal vaginal flora and promoted E. coli colonization [51].

RISK FACTORS FOR RENAL SCARRING — Renal scarring, the loss of renal parenchyma between the calyces and the renal capsule, is a potential complication of UTI. Long-term consequences of renal scarring may include hypertension, decreased renal function, proteinuria, and end-stage kidney disease.

General risk factors — The development of renal scarring has been associated with the following factors, which are modifiable to some extent:

Recurrent febrile UTI [52] (see "Urinary tract infections in children: Long-term management and prevention", section on 'Monitor for recurrent symptoms' and "Urinary tract infections in children: Long-term management and prevention", section on 'Prevention of recurrent UTI in children without vesicoureteral reflux')

Delay in treatment of acute infection; a delay in the treatment of febrile UTIs is associated with increased risk for renal scarring [53] (see "Urinary tract infections in infants older than one month and young children: Acute management, imaging, and prognosis", section on 'Empiric therapy')

Early initiation of UTI treatment requires that the diagnosis be considered even in the absence of symptoms referable to the urinary tract (eg, in the febrile infant or young child with or without a focus of infection). (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Clinical presentation'.)

Bladder and bowel dysfunction (see "Urinary tract infections in children: Long-term management and prevention", section on 'Identify and treat bowel and bladder dysfunction')

Modification of bladder and bowel dysfunction requires that it be recognized; presenting symptoms include daytime wetting, withholding behaviors, and constipation [36]. (See 'Bladder and bowel dysfunction' above.)

Obstructive urinary tract malformations (see "Clinical presentation and diagnosis of posterior urethral valves", section on 'Chronic kidney disease' and "Congenital ureteropelvic junction obstruction", section on 'Long-term outcome')

Obstructive urinary tract malformations generally are treated surgically. (See "Management of posterior urethral valves" and "Congenital ureteropelvic junction obstruction", section on 'Management'.)

Vesicoureteral reflux (VUR) (see "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Loss of renal parenchyma' and "Management of vesicoureteral reflux")

Young age has been shown to be associated with scarring in some studies [54-56], but not in others [8,53,57-63]. In a 2014 meta-analysis, older age was associated with renal scarring [8].

Prediction of renal scarring after first UTI — Predictors of renal scarring after a first UTI were investigated in a meta-analysis of individual patient data from nine studies including 1280 children (0 to 18 years) who underwent renal scintigraphy at least five months after their first UTI [8]. Renal scarring was present in 15.5 percent of children. Predictors of renal scarring included:

VUR – VUR, especially high-grade VUR, was associated with the development of renal scars (Grade I and II [odds ratio (OR) 1.8, 95% CI 1.2-2.8] and Grade IV and V VUR [OR 22.5, 95% CI 11.3-44.8])

Abnormal renal bladder ultrasonography (RBUS; OR 3.8, 95% CI 2.6-5.5)

Elevated inflammatory markers including a C-reactive protein of >40 mg/L (4 mg/dL; OR 3.0, 95% CI 2.0-4.6) or a polymorphonuclear cell count >60 percent (OR 1.9, 95% CI 1.3-2.8)

Temperature ≥39°C (102.2°F) (OR 2.3, 95% CI 1.6-3.3)

UTI caused by organism other than E. coli (OR 2.2, 95% CI 1.3-3.6)

Children with an abnormal RBUS finding or with a combination of high fever (≥39°C [102.2°F]) and an etiologic organism other than E. coli (which constituted 21.7 percent of the sample) represent a particularly high-risk group in whom the risk for renal scarring is 30.7 percent. Whether more aggressive management (eg, antibiotic prophylaxis, use of adjuvant corticosteroids [64,65], further imaging with dimercaptosuccinic acid or VCUG, and timely treatment of recurrent UTI) reduces the risk of renal scarring requires further study.

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SUMMARY

Prevalence

The prevalence of urinary tract infection (UTI) in febrile children younger than two years varies from <1 to 16 percent depending upon age, sex, and circumcision status in males (table 1). (See 'In young children with fever' above.)

The prevalence of UTI in older children with urinary tract symptoms and/or fever is approximately 8 percent. (See 'In older children' above.)

Microbiology – Escherichia coli is the most common bacterial cause of UTI. (See 'Microbiology' above.)

Host factors – A variety of host factors influence the predisposition to UTI in children. These include female sex, genetic factors, urinary tract anomalies, bladder and bowel dysfunction, vesicoureteral reflux (VUR), sexual activity, and bladder catheterization in addition to those mentioned above for febrile young children (eg, lack of circumcision, temperature >39°C [102.2°F]). (See 'Host factors' above.)

Bladder and bowel dysfunction is an important and often overlooked factor in the pathophysiology of UTI in children. It is characterized by an abnormal elimination pattern (frequent or infrequent voids, urgency, infrequent stools), bladder and/or bowel incontinence, and withholding maneuvers. (See 'Bladder and bowel dysfunction' above.)

Risk of developing renal scarring – Children with an abnormal renal ultrasonographic finding or with a combination of high fever (≥39°C [102.2°F]) and an etiologic organism other than E. coli have a higher risk of developing renal scarring than children without these characteristics. (See 'Prediction of renal scarring after first UTI' above.)

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Topic 5988 Version 32.0

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