Description

There are three kinds of UTI in children: asymptomatic bacteriuria, cystitis, and pyelonephritis. Young children may have limited or unusual symptoms; therefore, a high degree of suspicion must be maintained to diagnose UTI. Inflammation and infection can occur at any point in the urinary tract, so a UTI must be identified according to location. Asymptomatic bacteriuria is bacteria in the urine without other symptoms and is benign and does not cause renal injury. Cystitis is an infection of the bladder that produces lower tract symptoms but does not cause fever or renal injury (Elder, 2007d). Pyelonephritis is the most severe type of UTI involving the renal parenchyma or kidneys and must be readily identified and treated because of the potential irreversible renal damage that can occur. Clinical signs thought to be consistent with pyelonephritis include fever, irritability, and vomiting in an infant and urinary symptoms associated with fever, bacteriuria, vomiting, and renal tenderness. It is the most common cause of serious bacterial infection in infants younger than 24 months of age with fever without a focus (Elder, 2007d). A complicated UTI is defined as a UTI with fever, toxicity, and dehydration or a UTI occurring in a child younger than 3 to 6 months of age. The UTI may be classified based on its association with other structural or functional abnormality, such as VUR, obstruction, dysfunctional voiding, or pregnancy. Additionally, a UTI must be identified as a first occurrence, recurrent (within 2 weeks with the same organism or any reinfection with a different organism), or chronic (ongoing, unresolved, often caused by a structural abnormality or resistant organism). Finally, age and gender of the pediatric patient are important factors in determining the method of evaluation and the course of treatment.

Epidemiology

The organism most commonly associated with UTI is Escherichia coli (70%), although other organisms, such as Enterobacter, Klebsiella, Pseudomonas, and Proteus can be found. UTI secondary to group B streptococcus is more common in neonates. Several factors are believed to contribute to the etiology of UTIs. Most UTIs are thought to be ascending (i.e., the infection begins with colonization of the urethral area and ascends the urinary tract). If the infection progresses to the kidney, intrarenal reflux deep into the kidneys can lead to scarring. However, the most important risk factor for the development of pyelonephritis in children is VUR, which can be detected in 10% to 45% of young children who have symptomatic UTIs. Furthermore, reflux of infected urine from the bladder increases the risk of pyelonephritis. This damage to the kidney occurs in the composite papillae, which have wide and gaping openings allowing intrarenal reflux. The composite papillae are located in the upper and lower poles of the kidney, which is the usual site of scarring. Simple papillae have angled, slitlike openings that resist intrarenal reflux (Fig. 34-5).

FIGURE 34-5 Most renal papillae are conical, with papillary ducts that open obliquely into the renal pelvis (top). These do not allow intrarenal reflux. But some kidneys have compound papillae, formed by the fusion of conical papillae (bottom). These have papillary ducts with gaping openings at right angles to urine flow and do permit intrarenal reflux.

(From Ransley PG: Intrarenal reflux: anatomical, dynamic and radiological studies-part I, Urol Res 5:61-69, 1977.)

Host resistance factors and bacterial virulence factors are also important in the etiology of UTIs. Host resistance factors include the presence of a structural abnormality or dysplasia (such as VUR, obstruction, or any other anatomic defect) or the presence of functional abnormalities (such as dysfunctional voiding or constipation). Other factors affecting resistance include female gender (having a short urethra), poor hygiene, irritation, sexual activity or sexual abuse, and pinworms.

Several bacterial factors are known, but the two most important ones are adherence and virulence of the bacteria. Bacteria that have fimbriae or pili are able to anchor or adhere to the surface of the bladder mucosa. This adherence allows the bacteria to resist the bladder’s defensive cleansing flow of urine and causes tissue inflammation and cell damage. Adherence may also play a role in bacteria ascending the urinary tract. Virulence refers to the toxicity of substances released by bacteria. The greater the virulence, the greater the damage to the urinary tract. Both of these factors enhance colonization of the urinary tract and aid in the persistence and effect of the bacteria.

The risk of UTI in infants 2-24 months of age is about 5%. The incidence in females is more than twice that of males (2.27%); uncircumsized boys have a rate 4 to 20 times greater than circumsized boys (AAP, 2011). There is a greater frequency in premature and low-birthweight infants. Females older than 12 months of age have 2.1% prevalence; after the first year of life, it is also more common to find a UTI in females than in males with an overall incidence of 3% to 5% in girls and 1% in boys (Elder, 2007d). Ten percent of girls and 3% of boys will have a UTI by 16 years of age (Hutchings and Jadresic, 2010). The incidence of UTI is often increased in adolescent girls as they become sexually active. Recurrence is common, often within the first year after the initial infection.

Clinical Findings

History

The following information should be obtained:

• Family history of VUR, recurrent UTI, or other kidney problems

• Prenatally diagnosed renal abnormality

• Previous infection: Request records from the evaluation of past infections and diagnostic studies performed

• Circumcision

• Risk factors for infants 2-24 months of age with no other source of infection (AAP, 2011)

Female—white race, age <12 months, temperature ≥39°C, fever ≥2 days

Male—nonblack race, temperature ≥39°C, fever >24 hours

• Hygiene habits: Wiping front to back

• Voiding patterns: Frequency, abnormal stream, complete emptying, dribbling, and enuresis

• Constipation, perianal itching (pinworms)

• Irritants such as nylon underwear or clothing (spandex, tight pants or shorts that rub); bubble bath

• High blood pressure

• Sexual activity or sexual abuse

• Other infection: Pinworms, diaper rash

Physical Examination

See Table 34-2 for age-related symptoms.

• General appearance (toxic appearing?)

• Vital signs: Temperature, blood pressure

• Growth parameters: Growth may be decreased with chronic UTI or renal insufficiency, especially in infants

• Flank pain or tenderness in the costovertebral angle

• Abdominal examination: Suprapubic tenderness, bladder distention or a flank mass (obstructive signs), mass from fecal impaction

• Genitalia: Vaginal erythema, edema, irritation, or discharge; labial adhesions; uncircumcised male, urethral ballooning; weak, dribbling, threadlike stream

• Neurologic examination (if voiding is dysfunctional): Perineal sensation, lower extremity reflexes, sacral dimpling, or cutaneous abnormality

TABLE 34-2 Clinical Findings of Urinary Tract Infection in Children of Various Ages

Diagnostic Studies

The method used to collect urine has an effect on the interpretation of results. It is acceptable to collect urine for urinalysis only from a non–toilet-trained child by using a sterile, adhesive bag carefully place over well cleaned genitals. If the bagged urine results in a positive leukocyte esterase or nitrite test, a child younger than 24 months of age has risk factors, or the patient is symptomatic additional urine should be collected by sterile catheterization or suprapubic aspiration. The National Collaborating Center for Women’s and Children’s Health (2007) recommends that prior to suprapubic tap an ultrasound should be used to confirm urine in the bladder. Older children, who can void on command, should be able to obtain a clean-catch void. Having the female child sit backward on the toilet separates the labia and decreases contamination. See the diagnostic studies section earlier in this chapter for other pertinent information.

• UA should be used only to raise or lower suspicion. Suspicious findings include foul odor, cloudiness, nitrites, leukocytes, alkaline pH, proteinuria, hematuria, pyuria, and bacteriuria.

Nitrite chemical tests are reliable on urine specimens when gram-negative bacteria are present and when the urine has been in the bladder for 4 hours or longer. False-positive results are rare, whereas false-negative results are common.

Leukocyte esterase chemical tests detect pyuria, but pyuria may arise from causes other than UTI.

• Microscopic evaluation of uncentrifuged urine is helpful if bacteria are seen.

• Urine culture by standard culture methods or by dipslide is essential to confirm the diagnosis. See Table 34-3 for evaluation of culture results.

• Gram stain is helpful if bacteria are identified.

• Bacterial identification and determination of sensitivities are necessary in patients who appear toxic or could have pyelonephritis, have relapses or recurrent UTI, or are nonresponsive to medication.

• Complete blood count (CBC) (elevated WBC count), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), BUN, and creatinine should be done if the child is less than 1 year of age, appears ill, or if pyelonephritis is suspected.

• Serum procalcitonin level of more than 0.5 ng/mL is an accurate and reliable biologic marker for renal involvement during a febrile urinary tract infection, pyelonephritis, and with renal scarring, so it may be useful in the clinical diagnosis and treatment of UTIs (Bressan et al, 2009; Cataldi et al, 2010).

• Blood culture should be done if sepsis is suspected or if the young child is unimmunized (see Chapter 23).

TABLE 34-3 Criteria for Diagnosis of Urinary Tract Infections

Method of Collection	Colony Count (Pure Culture)	Probability of Infection (%)
Suprapubic aspiration	Any organism	>99
Catheterization	>10,000	95
	≥10,000 to 100,000	Infection likely, especially if obstruction or if voids frequently
	1000 to <10,000 single organism	Suspicious, repeat
	<1000	Infection unlikely
Clean Voided
Boy	>10,000 single organism	Infection likely
Girl	Three specimens, >10,000	95
	Two specimens, >100,000	90
	One specimen, >100,000	80
	50,000 to 100,000	Suspicious, infection possible, repeat
	10,000 to 50,000	Suspicious, if symptomatic, repeat
	10,000 to 50,000	Infection unlikely if asymptomatic
	<10,000	Infection unlikely

From Tan JM: Nephrology. In Custer JW, Rau RE: The Harriet Lane handbook, ed 18, Philadelphia, 2009, Mosby.

Differential Diagnosis

The differential diagnosis includes urethritis, vaginitis, viral cystitis, foreign body, sexual abuse, dysfunctional voiding, appendicitis, pelvic abscess, and pelvic inflammatory disease. Any child who has acute fever without a focus, FTT, chronic diarrhea, or recurrent abdominal pain should be evaluated for UTI.

Management

Goals of treatment are to quickly identify the extent and level of infection; to treat appropriately to eradicate infection; to provide symptomatic relief; to find and correct anatomic or functional abnormalities; and to prevent recurrence and new or progressive renal damage (AAP, 2007). When deciding on a treatment plan, the child’s age, sex, symptoms, the suspected location of the UTI and antibiotic resistance patterns in the community must be considered. Figure 34-6 outlines treatment of UTI in the child.

FIGURE 34-6 Suspected urinary tract infection (UTI) less than 5 years of age.

• Follow-up urine culture should be done 48 to 72 hours after initiating treatment, especially if symptoms persist or organism resistance is found in the community. If the culture is sterile, continue antibiotic therapy.

If the culture is not sterile or if no clinical improvement is seen, urine should be sent for bacterial identification and sensitivity studies, and an alternative broad-spectrum antibiotic should be used pending those results. Culture should again be repeated after 48 to 72 hours and, if sterile, antibiotic therapy continued.

Follow-up cultures should be obtained 3 to 4 days after finishing antibiotic treatment.

Repeat urine culture should be done with any fever, illness, dysuria, or frequency.

• Radiologic workup (Table 34-4):

Children younger than 5 years of age or any child with a febrile UTI should have a renal and bladder ultrasound as soon as the urine is sterile or when the prescribed antibiotic has been completed (Elder, 2007e; Feld and Mattoo, 2010). Waiting 2 to 6 weeks after infection may be recommended to allow any inflammatory changes to subside. VCUG may be done prior to discharge in a hospitalized child.

VCUG does not need to be done routinely with first febrile UTI. However, if US reveals hydronephrosis, scarring or other atypical or concerning findings, VCUG should be completed.

DMSA scan may be recommended for children with a febrile UTI or when a diagnosis of pyelonephritis is uncertain; it is ideally done 6 months after the infection (Elder, 2007e; Feld and Mattoo, 2010; Lee et al, 2009).

TABLE 34-4 Radiologic Studies Done for Evaluation of Urinary Tract Infection

Patient Education, Prevention, and Prognosis

The following should be discussed with parents and/or patients:

According to Fitzgerald and colleagues (2009), “The relationship between UTI, renal scarring, and VUR is unclear, as is the progression of uncomplicated UTI to pyelonephritis and subsequent damage to the kidneys.” Major risk factors for renal damage include delay in treatment of pyelonephritis, younger than 1 year of age, anatomic or neurogenic obstruction, severe reflux, dysplasia, and multiple infections. The same acute inflammatory process responsible for eradication of bacteria is also responsible for damage to renal tissue and subsequent scarring.

Description

VUR is regurgitation of urine from the bladder up the ureter to the kidney. The major concern with VUR is the exposure of the kidney to infected urine (Feld and Mattoo, 2010). Primary VUR is the most common type and is typified by a congenital, abnormally short ureter and ineffective valve. Secondary VUR is due to bladder outlet obstruction and can be functional or structural. It is graded according to an international classification (Fig. 34-7). Grade I does not reach the renal pelvis; grade II extends up to the renal pelvis without dilation; grade III describes reflux to the renal pelvis with mild to moderate dilation of the ureter and the renal pelvis; grades IV and V (high grade) include definite distention of the ureters and renal pelvis and can include hydronephrosis or reflux into the intrarenal collecting system (Elder, 2007e).

FIGURE 34-7 International reflux grading. Grade I: Ureter only. Grade II: Ureter, pelvis, and calyces; no dilation, normal calyceal fornices. Grade III: Mild or moderate dilation or tortuosity (or both) of ureter, and mild or moderate dilation of renal pelvis but no or slight blunting of the fornices. Grade IV: Moderate dilation or tortuosity (or both) of ureter and moderate dilation of renal pelvis and calyces. Complete obliteration of sharp angles of fornices but maintenance of papillary impressions in majority of calyces. Grade V: Gross dilation and tortuosity of ureter; gross dilation of renal pelvis and calyces; papillary impressions are no longer visible in majority of calyces.

(From Lebowitz RL, Olbing H, Parkkulainen KV et al: International system of radiographic grading of vesicoureteral reflux, International Reflux Study in Children, Pediatr Radiol 15[2]:105, 1985.)

Epidemiology

Reflux occurs because of congenital abnormalities and can persist with recurrent infection. Reflux provides a route for bacteria to ascend to the kidney and cause pyelonephritis. VUR is the most common anatomic abnormality found in young infants and children with UTI. Approximately 30% to 40% of siblings of children with reflux also have reflux, and 50% of children whose mothers have reflux also have reflux (Elder, 2007e). A meta-analysis identified that children who have UTIs more often and have associated bladder and bowel dysfunction (BBD) are more at risk for renal scarring (Peters et al, 2010).

Clinical Findings

Management

The goal of treatment is the prevention of infection and subsequent scarring. Early identification and appropriate treatment of infection achieve this goal. Table 34-5 presents a summary of the American Urological Association (AUA) guideline on management of primary VUR (Peters et al, 2010). The guideline statements are labeled as standards, recommendations, and options based on the level of evidence and degree of flexibility in application.

TABLE 34-5 Management of Primary Vesicoureteral Reflux in Children

Patient Education, Prevention, and Prognosis

• VUR does not cause scarring, infection does, but VUR is a risk factor for pyelonephritis and subsequent scarring.

• Screen all siblings younger than 3 years of age for VUR (Menezes and Puri, 2009).

• Management, prevention of UTIs, and compliance must be understood by families. The necessity of urine culture with any suspicious symptoms should also be emphasized. The potential for untreated, chronic UTI leading to chronic renal disease must be explained.

• Other points to emphasize include the following:

Prompt treatment of UTI should be instituted.

Prophylactic medicines are best given at night because of urinary stasis while asleep.

BP and growth should be monitored.

The guidelines discussed in the Patient Education and Prevention section of UTIs should be reviewed.

Preexisting renal damage may be present, and new renal scarring can occur. Children with grades I and II reflux usually have resolution of the reflux if infections are thwarted or treated early. Ten percent of children with renal scarring develop hypertension. Reflux nephropathy is a complication of VUR. Further complications related to scarring include end-stage renal disease (10%), growth failure, and decreased glomerular filtration rates (90%) (Nguyen, 2009).

Description

Hematuria is defined as the presence of five or more RBCs per hpf in three consecutive fresh, centrifuged specimens obtained over several weeks (Massengill, 2008). The number of RBCs per hpf considered to be abnormal varies and ranges from any to more than 5 per hpf in unspun urine to more than 5 to 10 per hpf in spun urine (Davis and Avner, 2007). For management purposes, hematuria in this text is defined as more than 2 RBCs per hpf in unspun or 5 per hpf in spun urine. The term gross hematuria is related to the concentration of RBCs rather than to the location or significance of the disorder. Brownish, tea-colored urine with casts or protein is usually glomerular in origin. Clots and red to pink urine with isomorphic RBCs but no protein usually originates from the lower tract. Factors causing hematuria can arise anywhere in the urinary system, from the urinary meatus to the kidneys. Urine can be discolored and urine dipsticks can be positive for RBCs when there is myoglobinuria or hemoglobinuria in which case no RBCs are seen on microscopic examination (Massengill, 2008). It is necessary to confirm the diagnosis of hematuria. Hematuria can be microscopic or macroscopic. Microscopic hematuria may be either persistent or transient.

Epidemiology

The causes of macroscopic hematuria include hypercalciuria (23%), immunoglobulin A (IgA) nephropathy (16%), glomerulonephritis (GN) (9%), and no known cause (38%). UTI, hydronephrosis, tumor, cystitis cystica, polyps, or epididymitis are characterized by macro-hematuria less than 1% of the time (Halverson and Alper, 2006). However, according to Bloom and Kolon (2005), 50% of children with gross hematuria have UTIs. The incidence of hematuria is 0.5% to 2% when confirmed with repeat UA (VanDeVoorde and Bissler, 2006).

Clinical Findings

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