Chapter 132: Urinary Tract Infection in Infants and Children

Pediatric urinary tract infections (UTIs) are now the most common serious bacterial infection in young children, since the introduction of successful immunizations and the resultant decrease in pediatric sepsis, meningitis, and occult bacteremia. UTIs should be considered as a possible diagnosis in all febrile infants and young children presenting to EDs and in all older children with abdominal or urinary symptoms whether or not there is fever.

Estimates of UTI prevalence are highly variable depending on the population. Pediatric UTI occurs in up to 8% of febrile children presenting to the ED with no obvious source of infection.^1,2,3 Approximately 1% of boys and 3% of girls are diagnosed with a UTI before puberty.⁴ The highest incidence occurs during the first year of life for both genders.³ Some of the baseline characteristics that increase the risk of UTI are listed in Table 132-1.^{1,2,5,6,7,8,9,10,11} It is unclear why African American children have a lower risk of UTI, but this difference is consistently noted.¹¹

Bacteria most commonly cause UTIs, although viruses and other infectious agents can also be urinary pathogens. The vast majority of UTIs in all age groups typically occur from retrograde contamination of the lower urinary tract with organisms from the perineum and periurethral area. In neonates, however, UTIs typically develop after seeding of the renal parenchyma from hematogenous spread.

Escherichia coli is the most common cause of UTI in children, and this is likely because of its ubiquitous presence in stool combined with bacterial virulence factors that improve adhesion to and ascent of the urethra.⁴ Additional pathogens include Klebsiella, Proteus, and Enterobacter species. Enterococcus species, Staphylococcus aureus, and group B streptococci are the most common gram-positive organisms and are more common in neonates. Staphylococcus saprophyticus can cause UTI in adolescents, and Chlamydia trachomatis may be present in adolescents with urinary tract symptoms and microhematuria. Adenovirus may cause culture-negative acute cystitis in young boys.

Mechanical defenses in humans, such as normal urinary outflow, clear most bacteria that are introduced into the bladder. Anatomic abnormalities can make bacterial proliferation or persistence in the bladder more likely. Additional factors influencing the development of UTI include virulence of the pathogen, vesicoureteral reflux, urolithiasis, poor hygiene, voluntary urinary retention, and abnormal bladder function due to constipation. There are occasionally patients, usually preschool- or school-aged females, who have recurrent UTI without a clear anatomic abnormality or identifiable risk factors. Genetic investigation may allow identification of these at-risk individuals.¹² Rare causes of UTI in children include indwelling urinary catheters or UTI from embolism or secondary to infection of other body areas.

HISTORY AND COMORBIDITIES

Clinical features vary markedly by age. The initial history should focus on the acute illness, including the presence of fever, vomiting, or abdominal pain, and questioning about symptoms that might suggest another source of fever such as rhinorrhea, cough, or diarrhea. Neonates with UTIs may appear septic, with fever, jaundice, poor feeding, irritability, and lethargy.¹³ Older infants and young children typically develop GI complaints, with fever, abdominal pain, vomiting, and change in appetite. GU symptoms in a verbal child should always trigger consideration of a UTI. In school-aged children and adolescents, cystitis and urethritis (lower tract disease) typically present with urinary frequency, urgency, hesitancy, and dysuria. Pyelonephritis (upper tract disease) typically presents with fever, chills, back pain, vomiting, and dehydration. In nonverbal children, a history of high (>40çC [104çF]) or prolonged fever appears to be one of the most predictive symptoms of UTI.¹¹ A parental report of "smelly" urine does not appear to be helpful.¹⁴

Medical history should include a prenatal history and ascertainment of whether a late-term prenatal US was obtained. A normal late-term US decreases the likelihood of some GU abnormalities that increase the risk of UTI. Additionally, a previous history of UTI and family history of UTI is important to guide subsequent evaluation.

PHYSICAL EXAMINATION

Assess the child's health and degree of acute illness. If the child is lethargic, dehydrated, or in respiratory distress, then institute appropriate therapy. Examine the genitalia for anatomic abnormalities (e.g., labial adhesions, phimosis) or other causes of GU symptoms. Note circumcision status in male infants. Perform a careful abdominal and groin examination to evaluate for suprapubic tenderness,¹¹ costovertebral angle tenderness, hernias, and any abnormal masses. A complete physical examination helps to exclude other causes of illness. Although the presence of another source of fever lowers the risk of UTI, it does not eliminate it, and UTI can coexist with common viral syndromes such as respiratory syncytial virus bronchiolitis.^11,15,16

In infants and young children, the only cardinal feature of UTI is a febrile illness without other definitive source. The approach to neonates and infants <3 months of age with fever and no identifiable source is discussed in detail in chapter 116, Fever and Serious Bacterial Illness in Infants and Children. Urine testing (including urine chemical strip testing, microscopy, and culture) is an important part of a more comprehensive evaluation in this age group. As mentioned earlier, UTI should be considered in infants with bronchiolitis, particularly in the presence of high fever (temperature of 40°C [104°F]).^16,17 In verbal children, dysuria combined with suprapubic tenderness on examination is the classic constellation of symptoms and signs.

There are no clinical criteria that confirm the diagnosis of UTI in children without urinary testing and culture.¹⁸ Evidence-based clinical practice guidelines for the evaluation and treatment of pediatric UTI from the American Academy of Pediatrics are limited to infants and young children 2 to 24 months of age and require both pyuria and bacteriuria with ≥50,000 colonies/mL of a single uropathogenic organism (in a properly collected specimen, <1 hour old at room temperature and <4 hours old refrigerated) for definitive diagnosis of UTI.¹⁹ Positive urine cultures in the absence of pyuria/bacteriuria may represent asymptomatic bacteriuria. For infants <2 months old, a positive urine culture is the gold standard for diagnosis.

In adolescents, symptoms of dysuria without vaginal or urethral discharge, or an examination consistent with UTI/pyelonephritis, such as suprapubic or costovertebral angle tenderness, in the presence of a positive urine chemical strip for pyuria and/or nitrites, allow a presumptive diagnosis of UTI. A careful sexual history (with assurance of confidentiality and respect for privacy) is important in this age group, because urethral symptoms (such as dysuria) may predominate in both UTI and sexually transmitted infections. Urine culture remains important for definitive diagnosis, and pyuria without uropathogenic culture growth may suggest sexually transmitted infection. Consider pelvic examination for sexually active girls and appropriate testing in both boys and girls with dysuria who are sexually active (see chapter 149, Sexually Transmitted Infections).

DIFFERENTIAL DIAGNOSIS

UTI is a possible diagnosis in all infants with fever. In children with dysuria but no fever, the most common concerns are listed in Table 132-2.

LABORATORY EVALUATION

Urine Sample Collection

If children can void on command, then attempt collection of a spontaneously voided specimen. Perineal cleaning before voiding reduces the rate of false-positive urinary dipstick tests and the rate of contaminated culture results.²⁰

In infants and children who are not able to void on command, bladder catheterization is the preferred method for urine collection. Suprapubic aspiration, although invasive, is also acceptable. The value of perineal bag specimens is limited by the high false-positive results and low specificity. Although the sensitivity of perineal bag specimens for UTI is generally similar to that collected from catheterized or suprapubic specimens, the specificity is low, and a positive culture result from a perineal bag specimen has a high likelihood of significant contamination with perineal bacterial flora. The only (rare) circumstance where a perineal bag specimen may be used is to exclude disease when the pretest probability of UTI is very low, in which case a negative test rules out disease; if the results from a perineal bag specimen are positive, confirmation before giving antibiotics requires culture of a specimen collected in a sterile manner. Due to this diagnostic delay, many clinicians prefer obtaining a definitive specimen initially.

Urine Culture

The definitive test for UTI is a urine culture, and colony counts indicating infection are based on the type of sample collection (Table 132-3). Do not give antibiotics until a urine culture is obtained using a sterile method (bladder catheterization or suprapubic aspiration; see Procedures later). Based on the clinical scenario, length of illness, and urinalysis results, lower colony counts or mixed-growth cultures cannot necessarily be dismissed. Gram-negative urine culture results are usually available within 24 hours of the time that the culture plate is prepared.

Colorimetric or Chemical Test Strip Testing and Microscopic Analysis

Urine culture results are not available at the first ED visit, so chemical test strips that can detect leukocyte esterase and urinary nitrites, in conjunction with microscopic urinalysis, help predict the results of the urine culture. Leukocyte esterase is an enzyme found in some white blood cells, and its presence on testing suggests pyuria. Nitrite in the urine depends on coagulase-splitting bacteria that can reduce urinary nitrate to nitrite. Enterobacteria generally reduce nitrate to nitrite if the urine has been in the bladder long enough (about 4 hours), but most gram-positive bacteria do not reduce nitrate to nitrite, so nitrite testing has insufficient sensitivity for detection of UTI (53%; range, 15% to 82%).¹⁹ Urinary nitrites and leukocyte esterase alone are not sensitive markers for children who empty their bladders frequently. Urinary nitrites are highly specific (98%; range, 90% to 100%)¹⁹ and are therefore helpful when positive.²¹ Microscopy of spun or unspun urine for leukocytes and bacteria and/or Gram stain of unspun urine are also helpful for immediate diagnosis; urine Gram stain performs as well as a chemical test strip for urine infection.²² Gram stain can also identify the bacterial morphology and help guide appropriate initial antibiotic therapy. Table 132-4 summarizes the test characteristics of the urinalysis.

Regardless of the results from chemical testing strip or microscopic analysis, send the sample for a urine culture. There are two situations where one might not send urine for culture: (1) in low-risk patients with a completely normal urinalysis and another explanation for the symptoms; and (2) in older adolescent females with a very high posttest probability of UTI, without severe illness or complicating medical problems, and in an area with a predictable antibiotic resistance pattern. Because pyuria alone does not confirm a UTI, refer to Table 132-2 for some causes of culture-negative pyuria.

Imaging

Acute imaging of the urinary tract is rarely necessary in UTI assessment or treatment. If children have persistent fever or are worsening despite appropriate therapy or symptoms are unusually severe, then renal US is indicated to rule out abscess, stone, or obstruction. A renal US and bladder US are recommended for children 2 to 24 months old after the first UTI.¹⁹ Routine urethrocystography after first UTI is not recommended.¹⁹ Voiding cystourethrography is indicated if renal-bladder US reveals hydronephrosis, scarring, or other findings that would suggest either high-grade vesicourethral reflux or obstructive uropathy. This testing is arranged on an outpatient basis or is performed during hospitalization and is not typically facilitated from the ED. Some expert groups recommend against imaging after the first UTI, if the infection follows a typical clinical course. In Britain, US is recommended in the setting of atypical response to therapy or recurrent infection.^23,24

Other Suggested Testing

Testing beyond urinalysis and culture is not necessary for afebrile children with isolated UTI before initiating treatment. Children with atypical presentations or significant comorbidities may require further investigation as directed by the clinical picture. Febrile neonates and young infants (<2 months of age) require further evaluation prior to initiating antibiotics. Approximately 10% of young infants with febrile UTI admitted to the hospital demonstrate a sterile cerebrospinal fluid pleocytosis thought to be due to systemic release of inflammatory mediators.^27,28 Less than 1% of febrile infants with UTI will also have bacterial meningitis. Perform lumbar puncture and obtain blood cultures in febrile infants <1 month old with UTI before starting empiric antibiotics (see chapter 116). Lumbar puncture is not needed in febrile older infants and children with UTI unless there are signs or symptoms suggestive of meningitis, or if the child is clinically ill or the illness does not respond to treatment.²⁹

Most febrile infants with UTI have upper tract involvement, and laboratory tests are unlikely to differentiate those with bacteremia from those without bacteremia.³⁰ About 5% to 10% of febrile infants with UTI have bacteremia.²⁷ There is low risk of bacteremia and adverse events in well-appearing infants and children with febrile UTI.^29,31,32 For older patients being sent home for UTI treatment who have been initially committed to oral antibiotics, a blood culture is not likely to be helpful.

Do not give antibiotics to children until a urine culture is obtained, because typical choices for antibiotics will likely sterilize the urinary tract and make bacteriologic diagnosis impossible.¹⁹ Treatment and disposition depend on the age of the patient and severity of the illness. Most children can be treated orally.^33,34,35 Goals of therapy are to reduce symptoms/eliminate the acute infection, prevent complications and septicemia, and decrease the risk of renal scarring. Pyelonephritis can be demonstrated by renal scan in up to 61% of children <2 years old with febrile UTI, so children <2 years old with UTI have presumptive pyelonephritis.³⁰ Renal scarring is associated with adverse long-term outcomes such as hypertension, proteinuria, risk of preeclampsia in pregnant women, and eventual renal insufficiency. Treatment guidelines for first UTI are listed in Table 132-5, and Table 132-6 lists suggested parenteral and oral antibiotics. For children with relapsing or recurrent UTI or with underlying GU anatomic abnormalities, treat according to culture and sensitivity reports.

E. coli is the most common etiologic agent causing UTI, so antibiotics should be directed toward its eradication. Due to regional variation in antimicrobial susceptibility, physicians should be familiar with the local susceptibilities of the common urinary pathogens in their geographic region. Medications listed in Table 132-6 are generally acceptable, but emerging resistance is a continuing problem. Local sensitivities should guide antibiotic selection. Typical effective first-line agents to treat E. coli include cephalosporins, aminoglycosides, and extended-spectrum penicillins. Many strains of E. coli are now resistant to amoxicillin and trimethoprim-sulfamethoxazole, limiting the use of these two agents for empiric UTI treatment. A fluoroquinolone should be used in children only if sensitivities indicate that this is the only effective agent. Agents that do not achieve therapeutic concentrations in the bloodstream, such as nalidixic acid or nitrofurantoin, should not be used for UTI in febrile children. Once culture results with sensitivities for the infection are known, antimicrobial therapy should be tailored and simplified, based on the actual bacteria isolated. Children with anatomic urinary tract abnormalities need individualized treatment.

Enterococcus faecalis is a gram-positive organism that can cause UTI in children approximately 5% of the time,³⁷ and S. saprophyticus can cause UTI in adolescents. When Enterococcus is suspected because of prior infections with that organism, or gram-positive bacteria are identified on urine Gram stain, add ampicillin/amoxicillin or vancomycin to other therapy. The presence of Enterococcus increases the likelihood of an underlying urinary tract abnormality in a patient.³⁶ S. saprophyticus is typically sensitive to standard treatments.

All neonates (<1 month old) and children with UTI who appear ill or septic should be hospitalized for parenteral antibiotics and fluid resuscitation and to guard against worsening of shock when endotoxins are released after antibiotics lyse gram-negative bacteria. Children over 1 month of age with uncomplicated UTI may be appropriate for outpatient care with oral antibiotics if they appear well, can tolerate oral medication, are not dehydrated, and are not immunocompromised. They may receive a single dose of IM or IV ceftriaxone (50 milligrams/kg) in the ED and start on outpatient oral antibiotics. Length of antimicrobial therapy should be 7 to 14 days with close pediatric follow-up to ensure appropriate antibiotic use and to consider the need for imaging. Adolescent girls (>13 years old) with UTI may be treated like adults with the option for a 3-day oral antibiotic regimen.

PEDIATRIC UTI WITH UROLITHIASIS

Although uncommon, urolithiasis occurs in children, and the incidence is increasing and may be associated with the increasing prevalence of childhood obesity.^38,39,40 Children with symptoms suggestive of urolithiasis (colicky abdominal or flank pain, often radiating to the groin, and gross or microscopic hematuria) require imaging to evaluate for the possibility of stones. While noncontrast enhanced CT is the imaging modality of choice in adults, consideration of the potential long-term effects of radiation exposure must be weighed carefully, and renal US or MRI should be considered as alternatives.⁴¹ In the setting of fever, pyuria, and an obstructing stone, initial treatment should be parenteral with inpatient management and consultation with pediatric urology. Additional urine studies may be obtained to identify predisposing factors and chemical composition of stones, which may guide future management.

Practice parameters for the diagnosis, treatment, and evaluation of an initial UTI in febrile infants and young children are available from the American Academy of Pediatrics¹⁹ and the Royal College of Obstetrics and Gynaecology.²³