Urinary Tract Infections, Renal Abscess, and Other Complex Renal Infections

Infections of the genitourinary tract in children remain a significant health concern, accounting for 52–56 hospitalizations per 100,000 children with the majority of these children <2 years old, and more than 1.1 million US physician visits annually. Of all infectious agents, bacteria are the most common cause of urinary tract infection (UTI). In infants, UTI is a common cause of fever and may result in renal parenchymal damage and functional loss. As such, rapid diagnosis, proper treatment, and prevention of recurrent UTI are key to reducing renal damage.

Etiologic Agents

Under routine circumstances the most common bacteria that cause UTI are gram-negative Enterobacteriaceae, primarily Escherichia coli and then Klebsiella , Proteus , Pseudomonas, and Enterobacter spp. Some serotypes of E. coli , including uropathogenic E. coli (UPEC) and extraintestinal E. coli, contain specific cell wall O-antigens that facilitate infection. Gram-positive organisms other than Enterococcus spp. are less common causes of UTI, and isolates such as Staphylococcus saprophyticus account for only 15% of pediatric UTIs. Staphylococcus aureus, including methicillin-resistant strains, rarely cause symptomatic UTI, and isolation in the urine in a patient who has not been recently catheterized should suggest primary infection elsewhere. Infections caused by Pseudomonas spp. should be considered in children who have been hospitalized recently, had prior episodes of UTI, or had prior antibiotic treatment.

Epidemiology

UTI accounts for 2.4%–2.8% of pediatric physician visits, 52–56 hospitalizations per 100,000 children, and 201–223 hospitalizations per 100,000 children <2 years annually. ^, Girls are hospitalized twice as often as boys even though during the first year of life boys have more UTIs than girls. ^, For uncircumcised boys the risk for UTI is >10 times than for circumcised boys during the first year.

Definitions

Using routine culture techniques, normal urine shows no bacterial growth (i.e., <100 colony-forming units [CFUs]/mL for catheter-obtained specimens and <1000 CFUs/mL for clean-catch specimens). There is, however, controversy about whether urinary tract colonization (“benign bacteriuria”) occurs. UTI is diagnosed when an appropriately collected urinary specimen shows growth of a defined density for UTI diagnosis.

Because the anatomic level of UTI is difficult to determine without invasive cystoscopy or costly imaging, UTI —in this chapter and unless otherwise specified—refers to urinary tract bacteriuria with accompanying symptoms and signs—a spectrum from cystitis with lower tract bladder symptoms to pyelonephritis with systemic and abdominal symptoms.

Pathogenesis

UTI begins with bacterial adherence to host epithelial cells along a fecal-perineal-urethral route, with potential retrograde ascent of bacteria along the urinary tract. Aspects of bacterial virulence and patient risk factors influence this course but do not predict pyelonephritis, renal scarring, or parenchymal and functional loss. Of the 3% of girls and 1% of boys who have UTI prepubertally, about 17% will have infection-related renal scarring. Of children with scarring, 10%–20% may develop renal-related hypertension. A child rarely progresses to end-stage renal disease requiring transplantation because of UTI.

Bacteria must overcome urethral defenses to cause UTI. These defenses include (1) urethral washout, (2) epithelial shedding, and (3) paraurethral glandular secretion. Also, host defenses such as toll-like receptors triggered by bacterial lipopolysaccharide and urinary Tamm-Horsfall protein may adhere to uropathogenic E. coli and assist urethral washout.

Two important markers of E. coli virulence are mannose-resistant hemagglutination and P blood group−specific adhesion (P-fimbriae or P pili). Attachment between the uroepithelial cell and bacteria through type 1 pili (Fim pili) and fimbriae initiates a molecular interaction that allows for bacterial uptake into the umbrella cells on the bladder surface. The specific genotype of E. coli does not predict its virulence. Intracellular bacteria transform into biofilms that allow for microbial adaption and systemic infection, antimicrobial resistance through plasmid exchange, endotoxin production, and increased resistance to host systems. When in the bladder, retrograde ascent from the bladder to the kidney is affected by host immunity, impaired ureteral peristalsis, vesicoureteral reflux (VUR), and organism-specific uropathogenicity. Adhesion of bacteria to the renal collecting system epithelium occurs through Fim-like pili and P pili attachment to N-acetylgalactosamine and globoside moieties.

Risk Factors for Bacteriuria, Recurrent UTI, and Renal Damage

Age

The prevalence of UTI in both males and females younger than 1 year of age is higher than at any other time during childhood. This may be due to a number of factors including the density of periurethral colonization, lack of breastfeeding, immature immune status, and, in boys, the circumcision status.

Circumcision

The 2012 recommendations of the American Academy of Pediatrics (AAP) state that “health benefits of newborn male circumcision outweigh the risks, and the benefits of newborn male circumcision justify access to this procedure for those families who choose it.” They recommend that clinicians give educational material to parents and that parents determine what is in the best interest of their child. The AAP concludes that circumcision may reduce the risk for UTI and sexually transmitted infections such as HIV, herpes simplex virus type 2, human papillomavirus, and invasive penile cancer. Others note that no data exist from prospective randomized trials, and the interpretation may reflect cultural bias. It is notable that several studies show that uncircumcised boys with antenatally detected hydronephrosis and with bladder outlet obstruction have increased the risk of developing UTI during infancy and researchers suggest that circumcision should be considered as a potential UTI intervention during infancy. ^,

Race and Ethnicity

In the United States, the Healthcare Cost and Utilization Project (HCUP) and Kids’ Inpatient Database show that those identified as Black (31.9/100,000), Hispanic (70.3/100,000), and Asian (34.1/100,000) had higher rates of UTI hospitalizations than whites (30.6/100,000). Studies show that black children have less VUR and renal scarring compared with other races. ^, ^, Although these studies were the best available data at the time of the writing of the AAP guidelines, these data may be flawed, due to selection and healthcare bias. It has been shown that nonclinical markers such as race/ethnicity, education, and socioeconomic standing may influence healthcare diagnoses and management and as such create misleading categorical data. Race or ethnicity needs further evaluation and reassessment.

Genetic Predisposition

Genetic factors that may predispose to UTI include blood group phenotypes, such as P1 blood group, ABO, Lewis secretor phenotypes, host genetic polymorphisms of adhesion molecules (ICAM-1), transforming growth factor-β, toll-like receptor, and vascular endothelial growth factor. Being younger than 15 years at first UTI (odd ratio, 3.9) and having a history of maternal UTI (odds ratio, 2.3) are risk factors for recurrent UTI in girls. Decreased expression of interleukin-8 receptors (CXCR1) on peripheral neutrophils regardless of the VUR status predisposes to pyelonephritis. ^,

Colonization

The incidence of UTI is higher during the first few months of life than at any subsequent time in a healthy childhood. During this time the periurethral area of healthy infants is extensively colonized with aerobic bacteria, such as E. coli , enterococci, and staphylococci. Periurethral colonization decreases to low density during the first year of life, and after the age of 5 years, colonization is associated with recurrent UTI. For the first 6 months of life, uncircumcised infant boys have greater periurethral colonization than circumcised boys ^, ; during this time, uncircumcised boys have more UTIs than circumcised boys. Similarly, labial adhesions in girls’ cap trap urine in the vulva, leading to colonization and subsequent symptomatic UTI.

Immune Status

After birth, levels of serum immunoglobulin G (IgG) and IgA fall to a nadir at 3 months and periurethral colonization is high. ^, During this period, breastfeeding may protect against UTI and other infections because immunoglobulins, particularly secretory IgA, and oligosaccharides in maternal milk may inhibit the adherence of E. coli to the uroepithelium. ^, Thereafter, children develop their own specific immunity.

Sexual Activity

Sexual activity is a risk factor for UTI. An upsurge of UTI in an adolescent may signal the onset of sexual activity ; the prevalence of Chlamydia is 13%–26% and Neisseria gonorrhoeae is 2%–10% in this population. Male and female teenagers who have dysuria, urinary frequency, or urgency should be evaluated for both UTI and sexually transmitted infections.

Obesity

Obesity can be associated with chronic indolent inflammation that increases susceptibility to infections. Compared with lean children, obese children have an 80% increased risk for developing cystitis, including those younger than 2 years and an almost 100% increased risk for developing pyelonephritis. ^, These findings mirror those in adults.

Genitourinary Anatomic and Functional Abnormalities

After a first UTI, 40%–56% of children have imaging abnormalities, ^, the most common abnormalities being hydronephrosis found in 34% and VUR in 30%.

The presence of VUR does not correlate with increased susceptibility to UTI but does correlate with an increased likelihood of developing pyelonephritis after bacteriuria. VUR is a congenital abnormality that results from immature or inadequate muscular support at the ureteral orifice, facilitating retrograde urinary flow from the bladder into the ureter and pelvicaliceal system. Thus, infected retrograde urinary flow can lead to pyelonephritis. Children with high-grade reflux appear to be at greater risk for renal damage compared with children with low-grade reflux. ^, Uropathogenic virulence may be more likely to predict development of pyelonephritis and subsequent nephropathy than the degree of reflux.

Whether related to neuropathic bladder dysfunction, ineffective spontaneous bladder emptying, or more subtle increased postvoid residual bladder urine with or without VUR, dysfunctional voiding is associated with increased UTIs.

Identifying anatomic or functional urinary tract abnormalities in the setting of UTI is important because correction can reduce the risk for persistent or recurrent infection. A nidus of bacterial persistence, such as struvite stones, papillary necrosis, or sites of poor antimicrobial penetration (poorly functioning duplicated segments), may be removed, or VUR causing recurrent pyelonephritis can be repaired. Ensuring that toilet-trained girls use proper perineal hygiene by wiping from front to back and that toilet trained uncircumcised boys keep their foreskins dry after urinating can decrease the bacterial load in the perineum and the foreskin, respectively. ^,

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