Primary care approach to urinary tract infection in children

History and physical examination

Clinical signs and symptoms of a UTI depend on the age of the child, location of the UTI (upper or lower UTI) and severity of the illness. Fever is not a feature in lower UTIs, which tend to present with local or voiding symptoms such as dysuria, frequency, urgency and suprapubic pain. Important points in history taking and physical examination are summarised in Tables I and II, respectively.

Table I

Important aspects of history taking for children with UTI.

Table II

Important aspects of physical examination for children with urinary tract infection.

The cardinal symptom of APN is high fever without an obvious source of infection, often with chills and rigors. Neonates often present with very non-specific symptoms such as unexplained fever (may be low grade), lethargy, irritability, vomiting or poor feeding. Less commonly, they can present with late-onset/prolonged jaundice or faltering growth. Screening for UTI is part of the workup for neonates or infants with prolonged jaundice and failure to thrive. In pre-verbal infants and toddlers, the presentation is also likely to be non-specific, including unexplained fever, diarrhoea, vomiting, abdominal pain, foul-smelling urine or faltering growth. In older (verbal) children and adolescents, symptoms and signs are more specific, including fever, dysuria, foul-smelling or cloudy urine, urgency, frequency, new-onset urinary incontinence, gross haematuria, abdominal or flank pain, and vomiting. According to guidelines from the American Academy of Pediatrics, factors that increase the likelihood of UTI include age of below 12 months, fever for more than 48 hours, no other apparent source of fever, and fever of or exceeding 39ºC.(7)

In history taking and physical examination, it is important to look for complications as well as predisposing factors for UTI. Acute complications include sepsis, renal abscess formation and acute kidney injury. A history of decreased urine output is significant and could be due to dehydration or acute kidney injury. On physical examination, physicians should look out for the child who has an ill appearance, is mottled, and has unstable vital signs (as tachycardia is the first sign of compensation in a child in shock) and decreased activity. Renal punch, usually performed in older children, may be positive in APN.

Predisposing factors of UTI in children include bowel and bladder dysfunction, urinary tract abnormalities, indwelling catheters, immunosuppressed status, being an uncircumcised boy, and a history of renal or bladder stones (Box 1). As part of history taking, it is important to ask about these risk factors, in particular antenatal history, including abnormal scans, drug history, a personal history of previous UTI and a family history of kidney problems. All children should have a thorough physical examination to look for findings that would suggest a complicated UTI. Palpation of the abdomen and pelvis is crucial, looking out for abnormal masses including ballotable kidneys, palpable fecal masses and a palpable bladder. A careful genitourinary examination should also be performed, assessing for abnormalities of the urethral opening, continuous dribbling of urine (which may be due to ectopic ureter), severe phimosis, balanitis, labial adhesions or vulvovaginitis. Examination of lower limb neurology and the spine is important. Signs of spinal dysraphism such as sacral dimples, subcutaneous lipomas, haemangioma, hyper- or hypopigmentation, and hair tufts may indicate occult spinal lesions.

The term bowel and bladder dysfunction is used to describe the spectrum of lower urinary tract symptoms that accompany bowel disturbance in the form of constipation and/or encopresis. It has been reported to be a key risk factor for recurrent UTIs in children.(8) Bowel habits should be taken as part of history taking. Fecal masses may be noted on physical examination in a child with constipation. Other predisposing factors include inappropriate perineal hygiene, inadequate fluid intake, and infrequent or incomplete bladder emptying. In adolescent patients, it may be appropriate to ask for their sexual history.

Investigations

Urine culture is the gold standard for diagnosing UTI.(9) In patients suspected of having a UTI, a screening urine dipstick test or urinalysis should be done. The technique for urine collection is primarily determined by whether the patient is toilet trained. In children who have not achieved urinary continence, this can be done using a urine bag. In toilet-trained children and adolescents, midstream clean-catch urine samples should be collected. If the results are suggestive of UTI with the presence of pyuria and/or nitrites, a properly collected urine sample should be sent for culture before starting treatment. If the child is clinically unwell, he/she should be referred to the emergency department, where urine specimens may be collected via catheterisation. If the child is otherwise stable, a clean-catch specimen may be obtained in the outpatient setting. As there can be a risk of culture contamination from clean-catch specimens, two separate specimens should ideally be obtained, with at least one specimen obtained prior to initiating antibiotics.

To collect a bagged specimen or midstream clean-catch specimen, the genitalia and perineum should be broadly cleaned with an antiseptic solution to decrease the rate of contamination (Figs. 2a and b). The toilet-trained child should urinate into a toilet or urinal. Midway through urination, a specimen should be collected into a sterile urine container. For the child who is not toilet-trained, diapers should be taken off and a midstream specimen collected opportunistically.

Fig. 2

Illustrations show the genitalia and perineum being cleaned with an antiseptic solution before obtaining a urine specimen. (a) For girls, the labia should be spread and the perineum cleansed 2–3 times with non-foaming antiseptic solution or mild soap. (b) For boys, the meatus should be cleansed 2–3 times with non-foaming antiseptic solution or mild soap. The foreskin should be retracted before cleansing for those who are uncircumcised. Ensure that the foreskin is reduced to its normal position so that a paraphimosis does not develop. (c & d) A urine bag is applied by removing the backing from the adhesive and applying it over the vulva or penis and scrotum. The bag is regularly monitored and removed once urination has occurred.

It is important to clearly label the method used for urine collection, as the diagnostic criteria may vary according to the method used (Table III). For urine culture, a fresh urine specimen is required. The specimen should ideally be collected and sent to the laboratory within two hours. If a container is given to parents to take home and collect the urine, proper instructions should be given regarding handling of the urine specimen and when to return with the specimen. The container should only be opened when they are about to collect the urine sample and closed immediately upon collection to minimise contamination. For the same reason, the inner surface of the container should not be touched. The midstream urine should be collected directly in the container.

Table III

Method of urine collection and interpretation.

Urine cultures should always be interpreted with clinical correlations. False positive urine culture can be due to contamination, while false negative results can be due to partial treatment or diluted urine. Up to 9% of patients with APN may have equivocal or negative urine culture results.(10) If urine cultures are negative or equivocal but suspicion of UTI is high, repeat urine cultures should be sent and the child referred to a tertiary hospital for further imaging. Viruses, urinary schistosomiasis and funguria are differentials in children with an appropriate history of exposure and high suspicion of UTI but negative urine cultures.

Treatment and follow-up

Timely antibiotic treatment is the cornerstone of UTI treatment and paramount in minimising complications. Most UTIs are caused by Escherichia coli and other enteric Gram-negative organisms, the majority of which are sensitive to gentamicin or cephalosporins. In younger infants (particularly in those aged < 3 months), Gram-positive cocci may cause UTI and thus ampicillin/amoxicillin may be added to cover for these organisms.(11)

Lower UTIs can be treated in outpatient settings with one week of oral antibiotics such as cephalexin or Bactrim, which is contraindicated in G6PD (glucose-6-phosphate dehydrogenase)-deficient patients.(12) Urine cultures should be actively traced to enable targeted antibiotic therapy, and the patient should be reviewed for resolution of symptoms.

Upper UTIs can be effectively treated with oral antibiotics in the outpatient setting for 14 days or inpatient with intravenous antibiotics, followed by oral therapy once the patient improves.(13) The decision on outpatient or inpatient therapy depends on a few factors. Inpatient parenteral therapy should be considered in acutely ill children, children who cannot tolerate oral therapy and those with complicated UTIs (Box 2). Internationally, there is no consensus on using age as a criterion for inpatient parental therapy.(1) In general, babies younger than six months of age should be admitted for septic workup and intravenous antibiotics. Follow-up assessment to confirm an appropriate clinical response should be performed 48–72 hours after initiating antimicrobial therapy in all children with UTI. They should be referred to a tertiary hospital for intravenous antibiotics if they fail to respond to oral antibiotics. Table IV summarises the commonly used antibiotics for uncomplicated UTI.(13)

Box 2

Indications for inpatient treatment:

Table IV

Commonly used oral antibiotics and recommended dosing for uncomplicated urinary tract infection (UTI).

Referring to a specialist

As a general rule, all patients with one episode of febrile UTI (upper UTI) and patients who have recurrent cystitis should be referred to a specialist clinic for further evaluation, ideally 4–6 weeks after infection.

Renal and bladder ultrasonography is non-invasive and can be used to evaluate renal parenchyma, renal size and urinary tract anatomical abnormalities. It is recommended after the first febrile UTI. To avoid false positive studies, it is usually done after the UTI has been treated, because acute infection can alter the size and echogenicity of the renal parenchyma and cause transient hydronephrosis.(7) Renal and bladder ultrasonography may be performed during the acute infection to look for renal abscess or pyonephrosis in patients who fail to respond to appropriate treatment or whose illness is more severe than expected. Dimercaptosuccinic acid (DMSA) imaging is a nuclear imaging study used to identify alterations in radiotracer uptake within the renal parenchyma. It is done 4–6 months post infection and is the gold standard for diagnosing renal scars. Micturating cystourethrogram (MCU) is the gold standard for diagnosing vesicoureteric reflux (VUR). It also detects abnormalities of the lower urinary tract. Indications for an MCU generally include atypical or complicated UTI, abnormal renal and bladder ultrasonography, and recurrent UTI.(7)

Secondary prevention

The role of antibiotic prophylaxis in paediatric UTI prevention has been widely debated over the past few decades. In the past, antibiotic prophylaxis was used to reduce the risk of recurrent UTIs and the subsequent developmental of renal scarring, which may in turn lead to renal dysfunction. However, recent studies have shown that although antibiotic prophylaxis may reduce the incidence of recurrent UTI, it did not reduce the risk of or protect against renal scarring. In addition, exposure to prophylactic antibiotics has been shown to increase the likelihood of resistant infections.(3) Locally, in view of some benefits shown in select patient populations, we usually start antibiotics prophylaxis in patients at risk of recurrent UTI, including those with underlying urinary tract abnormalities.

Treatment of constipation with stool softeners has been shown to effectively prevent recurrent UTI in children without urinary tract anatomical abnormalities.(14) Biofeedback training together with regular voiding has been successful in reducing recurrent UTIs in children with detrusor instability or other dysfunctional voiding.(15)

Routine circumcision in boys does not reduce the risk of UTI enough to justify the risk of surgical complications. However, it may considered for boys who have recurrent UTI or high-grade VUR in whom circumcision may be clinically beneficial.(16)

Other prophylactic therapies using methenamine, cranberry juice and probiotics have been evaluated in comprehensive studies and found to have insufficient evidence to support the use of such agents as prevention.(17-19)