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Urinary tract infections (UTIs) are a common childhood condition. This chapter discusses the diagnosis and management of UTIs in children, as well as the potential need for further investigations to diagnose underlying structural anomalies, vesicoureteric reflux or dysfunctional voiding in a child presenting with a UTI.

Genetics/Etiology

Overall, prepubertal girls have a higher risk of UTI than boys, but under a year of age, the incidence of UTI is higher in boys.

The incidence of UTI in girls is estimated to be 3% and in boys around 1% [1]. Up to 7% of girls and 2% of boys will have a culture-proven symptomatic UTI by age 6 years [2].

The risk of UTI also varies between different age groups. In uncircumcised infant males the incidence of UTI is 0.7%, higher than the 0.1-0.4% reported incidence in infant females [1]. The risk of UTI increases after infancy in females to 0.9-1.4% before age 5, and to 0.7-2.3% in school age girls. In contrast, the risk of UTI drops in males after infancy to 0.1-0.2% under age 5 and 0.04-0.2% in school age boys.

The incidence of UTI is noted to be higher in Caucasian girls and lower in African-American children [1].

Physiology/Pathophysiology

The pathogenesis of UTI involves an interplay between host factors as well as virulent properties of the causative pathogens. A UTI is most commonly due to ascent of bacteria from the perineum into the urinary tract, but seeding of the urinary tract can occur haematogenously as well [3]. Bacteria can be introduced iatrogenically with instrumentation of the urinary tract in surgery; or with catheters and stents within the urinary system.

Host factors that increase the risk of UTI include:

Obstructive uropathies leading to impairment of drainage and stagnation of urine such as posterior urethral valves, pelviureteric junction obstruction or vesicoureteric junction obstruction
Vesicoureteric reflux (VUR)
Functional abnormalities such as dysfunctional voiding and constipation, termed ‘dysfunctional elimination’
Neurogenic bladder
Urolithiasis
Catheter and stent use
Structural anomalies of the renal tract such as ureteroceles, multicystic dysplastic kidney or urachal remnants
Host immune compromise and comorbidities such as diabetes mellitus

Causative organisms display a variety of virulence factors that predispose to UTIs. E coli is the commonest pathogen causing UTIs in children, cultured in over 80% of cases [4]. E coli strains have adhesins such as P fimbriae and Dr haemagglutinin that enable attachment to host proteins. Other pathogens that commonly cause UTI include Proteus, Klebsiella and Enterococcus. Proteus organisms have the ability to ‘swarm’ and rapidly advance along the surfaces of catheters and stents [5].

Less common pathogens causing UTI include Pseudomonas and Staphylococcus aureus, and these are considered atypical UTIs [6]. Neonates have relatively higher rates of Group B Streptococcus UTI [7].

Diagnosis

The presentation of children with UTI varies greatly with age. Preverbal children usually present generally unwell with non-specific signs such as lethargy, fever, vomiting and irritability. Up to 5-13% of febrile children presenting to the emergency department will have a UTI, so one must always consider a UTI in the febrile child [8].

Older children may localise symptoms to the urinary tract and present with suprapubic pain, dysuria, frequency or loin pain.

As always, the history of the presenting complaint is a guide to diagnosing a potential UTI. Other specific points must be sought in the history to assess for possible underlying predisposing conditions.

Antenatal history

For numerous reasons, antenatal records are often not available. If possible, it is helpful to know whether there is a history of fetal hydroureteronephrosis or bladder abnormality,. as this may suggest a structural anomaly or underlying severe vesicoureteric reflux.

History of previous UTIs

Were these culture positive or treated on clinical suspicion only? What were the organisms cultured? Did the child require admission to hospital? Did the child undergo investigations after the UTI was diagnosed and treated and what did the investigations show?

History of predisposing conditions such as renal stones, spina bifida or congenital abnormalities

Children with neurogenic bladders from spina bifida often self-catheterize, and thus may be predisposed to UTIs. Children with a history of renal or bladder stones likewise may present with UTI.

Urinary stream, voiding pattern

Children with bladder dysfunction have an increased risk of UTI [9]. Children with bladder overactivity, detrusor sphincter dyssynergia, infrequent voiding or incomplete voiding are at increased risk of UTI [10]. Posterior urethral valves should be suspected in male infants with poor stream.

Constipation

Constipation is often present in children who have recurrent UTIs. There is an association between constipation, dysfunctional voiding, recurrent UTIs and VUR in children [11]. One or all of these components may be present. They are often described under the title of ‘dysfunctional elimination’ or ‘dysfunctional elimination syndromes.’

Family history of vesicoureteric reflux (VUR)

Pure primary vesicoureteric reflux may be present and may be an underlying factor in the child with UTI. If present, and in the presence of febrile UTIs, there is evidence that surgical intervention to correct the VUR will reduce the risk of pyleonephritis [12].

Physical Examination
In addition to a standard physical examination, the examination should include looking for loin tenderness, a palpable bladder or kidneys and the appearance of the external genitalia. Labial adhesions in females and congenital megaprepuce in males may be predisposing factors. The back should be inspected for evidence of occult spina bifida. The lower limbs and peri-anal area examined for subtle signs of neuropathy such as wasting of the calf muscles or absent an-cutaneous reflex.

Investigations

Investigations to confirm diagnosis of UTI

The diagnosis of UTI is usually confirmed on a urine sample sent for microscopy, culture and sensitivities (MCS). The acutely unwell baby or infant with fever is best referred to the emergency department of a secondary or tertiary paediatric centre, where a full septic screen is performed. In an infant too young to void on command, the gold standard specimen is a suprapubic aspirate of urine. If a suprapubic sample is not possible to obtain, a catheter specimen may be taken. Urine should be sent for urgent microscopy and culture in the unwell young infant. Bacteria seen on microscopy are 93% sensitive and 95% specific for a UTI [13].

A bag specimen has a high false positive rate due to contamination from the skin. A bag specimen is useful to exclude a UTI if the collected urine is culture negative [7].

In an older child able to void on command, as much as possible, a urine sample should be obtained as a clean catch mid-stream urine. If a clean catch cannot be obtained, a suprapubic aspirate or catheter specimen should be obtained. In the older child with localised signs and symptoms of UTI, urine is sent for routine microscopy, culture and sensitivities.

Ward urinalyses are not very sensitive or specific for confirming the diagnosis of UTI. One should be suspicious of UTI if bacteria, protein and white cells are present on the urinalysis. Positive nitrites on a dipstick are 99% specific in predicting a UTI, but if nitrites are negative, they are only 60% sensitive in ruling out a UTI [13].

A culture with a pure growth of more than 100,000 colony forming units per ml is generally considered a UTI, especially if supported by the presence of white cells in the urine on microscopy [14].

Investigations recommended in a child with proven initial UTI

Studies suggest that 21-50% of children with a UTI will have an underlying abnormality. About 10% of children presenting with a UTI will have an abnormal ultrasound finding which may or may not affect management [15, 16]. This includes abnormalities such as pelviureteric junction obstruction, vesicoureteric junction obstruction and posterior urethral valves in boys. For this reason, we recommend that all children presenting with an initial UTI should undergo renal ultrasound.

A renal ultrasound after initial UTI should be performed even if there is a history of normal antenatal ultrasound scans.

Up to 30% of children presenting with a UTI will have underlying vesicoureteric reflux (VUR) [15, 16]. 90% of this VUR is of lower grades, I to III. Ultrasound scans are not useful for assessing for the presence or grade of VUR. A micturating cystourethrogram (MCU) is the most useful test to assess for and grade VUR. An MCU is performed by catheterizing the bladder and filling it with contrast, followed by a voiding phase. Sedation may be required in some cases.

VUR and UTIs are associated with renal damage and scarring. It is estimated that 5% of children presenting with UTI will have associated renal scarring [17]. Delay in diagnosis and treatment of UTIs, and recurrent UTIs correlate more with renal scarring. However, it is now well known that renal scarring in children with VUR may be present even before a clinical UTI, suggesting pre-existing scarring or dysplasia of the kidney. This is especially common in young male infants with VUR. On the other hand, children with VUR and recurrent UTIs may not acquire renal scarring; whilst some children with no proven VUR may acquire renal scarring after UTIs.

With these variations, it is difficult to obtain data about the true risks of UTIs and the true role of associated VUR in the development of renal scarring.

The American Urological Association still recommends renal ultrasound and MCU for all children presenting with their first UTI between ages of 2 months and 2 years. When significant VUR is found operative treatment options include either endoscopic ureteric injection or open ureteric reimplantation [18].

The Royal College of Physicians in the UK in 1991 recommended screening children under 1 year of age with a renal ultrasound and MCU as well as a dimercaptosuccinic acid scan (DMSA) after a first UTI [19]. The more recent UK NICE guidelines from 2007 have changed this traditional view. In essence, the guidelines recommend imaging after a first UTI in children should be more directed and selective, based on the age of the child, whether the UTI was typical or atypical and the response to treatment. One must remember that guidelines such as NICE are guides and are not meant to be prescriptive, so individual cases must be dealt with on their merits.

There are no set guidelines in Australia, and Australian practice in terms of imaging children after their first UTI varies from centre to centre and practitioner to practitioner [20].

Our recommendation currently is to always obtain a renal ultrasound after an initial UTI. An MCU should also be obtained in the following situations:

Known anomaly on antenatal ultrasound scan – especially if dilated ureters are visible, or bladder or urethral abnormality is suspected
Abnormality noted on the post-UTI renal ultrasound
Strong family history of VUR and reflux nephropathy
Recurrent UTIs
Atypical UTI organism
Severe UTI requiring IV antibiotics
Geographical factors – it would be prudent to perform an MCU in children who have been diagnosed with a UTI who live in rural and remote and have to travel long distances to specialist health care
In any boy with any degree of bilateral hydronephrosis, or history of poor stream or voiding difficulties, to exclude the possibility of posterior urethral valves

A DMSA scan is performed in children who have documented VUR on MCU or the appearance of renal scarring suggested on renal ultrasound. The DMSA scan will give a clear idea of differential renal function and distribution of renal scarring. The timing of the DMSA is crucial. If done when the child is unwell DMSA can help to diagnose pyelonephritis and later to detect renal scarring.

Non-operative Management

Antibiotics are the mainstay of UTI management. In most children, broad spectrum antibiotics can be started once cultures have been collected, and then tailored according to the sensitivities once the results are obtained. Sick febrile children with clinically suspected upper tract infections often need admission to hospital for treatment with intravenous antibiotics. Children with suspected cystitis often can be managed with oral antibiotics. A proof of treatment urine culture obtained a week or two after treatment is of no proven benefit in the asymptomatic patient.

Interventional Radiology Management or Operative Management

Infection in the setting of obstructive uropathies (such as posterior urethral valves, PUJO or obstructed upper pole and ureter secondary to a ureterocele) often requires good drainage of the obstructed system in addition to the antibiotic treatment. This is especially important in the setting of pyonephrosis, where the child’s clinical behavior is similar to one having an abcess with high swinging temperatures.

Drainage of the urinary tract can be facilitated by:

Urethral catheters, such as in posterior urethral valves
Internal drainage using JJ stents, such as in VUJO or PUJO
External drainage using a nephrostomy tube such as in pyonephrosis secondary to PUJO
Formal stomas such as vesicostomy, ureterostomy or pyelostomy

The decision of how best to drain the infected obstructed system depends on the clinical circumstances of the child, and is usually made by the urologist after examination of the patient and review of relevant images.

Managing VUR and UTIs

Low grade VUR has a high chance of spontaneous resolution. For higher grade VUR, parents are usually given the choice of watching and waiting for possible spontaneous resolution, with or without prophylactic antibiotics, versus upfront surgical intervention.

Data from the Cochrane Review shows a 50% reduction in the risk of febrile UTIs in children after surgical treatment for VUR [12]. Surgical treatment options for VUR include:

Endoscopic injection of ureteric orifice with substances like Deflux or Vantris gel. This has an 80% success rate in correcting VUR with one injection. It is done as day-case surgery under general anaesthetic and injection can be repeated if VUR persists or recurs.
Open surgical ureteric reimplantation. This has a 98%+ success rate in correcting VUR. It involves a small suprapubic incision and 1-3 days in hospital recovering.

Prognosis, Outcome, Complications

Generally, the prognosis after a childhood UTI is good. 30-50% of children after an initial UTI will get a further UTI. Most of these recurrences occur within 3-6 months of the original UTI [21]. Underlying predisposing structural and functional factors must be sought for and treated accordingly.

5% of children will have renal scarring evident when diagnosed with their initial UTI [17]. Whilst it is well established that these scars are likely to be congenital, there is also good evidence for acquired scarring associated with VUR and UTIs. Long-term studies show that 12% of those with childhood UTIs have renal scarring, with the number increasing to 25% in those with recurrent UTIs [22, 23].

Renal scarring is further associated with hypertension or renal failure. In one long-term study of children with renal scarring after pyelonephritis in childhood, the risk of hypertension was 23% and of renal failure 10% [24].

As acquired renal scarring seems to correlate most with delayed diagnosis and treatment of UTI, the key to scar prevention is quick clinical diagnosis of UTI and early instigation of appropriate treatment [22].

There is some evidence that pregnant women who have renal scarring secondary to childhood UTI are more at risk of complications such as bacteriuria, acute pyelonephritis, hypertension and pre-eclampsia [25].

UTI Prevention
Commonly recommended practices to minimize the risk of UTIs include:

Prophylactic antibiotics

Up to now, there was no strong evidence to support the role of prophylactic antibiotics after a single UTI in preventing recurrences. A recent Australian randomized controlled trial is the first to definitively show a reduction in the risk of UTIs in the 12 months after the index UTI in the group of children placed on daily trimethoprim/sulphamethoxazole. However, the protective effect seemed to drop off with time, and the long-term benefit of antibiotic prophylaxis in children with UTIs remains unproven [6].

Managing dysfunctional elimination

Dysfunctional voiding with raised post-void residual urine volumes and constipation are associated with an increased risk of urinary tract infections and hence must be carefully investigated and managed, particularly in children who present with recurrent UTIs [26].

Cranberry

Cranberry contains anthocyanidin/proanthocyanidin moieties that are potent antiadhesion compounds and thought to prevent I and P-fimbriated uropathogens such as E coli from adhering to the urothelium. There is randomized evidence that cranberry helps reduce the risk of recurrent UTIs in adult women, and its value in children is extrapolated but not proven [27].

Probiotics

These are thought to promote the balance of bowel organisms in favour of non-pathogenic commensals.

Circumcision in male infants

Studies suggest that circumcised boys have a 10-fold lower risk of UTI compared with uncircumcised boys [28, 29]. However, there is no evidence to recommend circumcision for all boys after a first UTI. Circumcision is certainly considered in boys who experience recurrent UTIs and/or have underlying urinary tract anomalies such as posterior urethral valves or VUR.

Drinking plenty of fluids

This is to maintain regular voiding and flushing of the urinary tract.

Good toileting habits

These include regular voids (every 3 hours), relaxed seated posture for girls with feet supported and hips abducted and wiping the perianal area away from urogenital area.

References

29. Schoen, E.J., C.J. Colby, and G.T. Ray, Newborn circumcision decreases incidence and costs of urinary tract infections during the first year of life. Pediatrics, 2000. 105(4 Pt 1): p. 789-93. PMID: 10742321 - http://www.ncbi.nlm.nih.gov/pubmed/10742321

Urinary Tract Infection In Children