Dr James Larcombe explains that the new guideline from NICE will clarify diagnosis, treatment, and long-term management of urinary tract infections in children magic

In August 2007, the National Institute for Health and Care Excellence published a new guideline entitled Urinary tract infection in children: diagnosis, treatment and long-term management.1The guideline aims to clarify best practice for clinical diagnosis, urine collection, investigation, treatment, and long-term management of urinary tract infections (UTIs).1

Urinary tract infection is a common bacterial infection.1 By the age of 2 years, around one in 50 children will have had at least one UTI. This rate rises to one in 10 girls and one in 30 boys being affected by the age of 16 years.2

Boys suffer more UTIs in their first 3 months of life, whereas infection rates in girls peak later, at between 6 and 9 months of age.3 Structural urinary tract abnormalities predispose to infection and are more common in males, whereas shorter urethras predispose females of all ages to infection.

The significance of childhood UTIs

Urinary tract infections in childhood may carry special significance. Although the vast majority of children who have had a urine infection recover promptly and do not have any long-term complications, 4–5% of children with a history of UTI develop renal scarring.1 However, only a few will suffer long-term morbidity. The risks are greatest in very young children, and in those with more severe underlying abnormalities.1

Vesico-ureteric reflux (VUR) is not always implicated in renal scarring following UTI, but it has a very significant role.2 It occurs in 1–3% of the general population of children,4 and allows urine (and any bacteria) to pass in a retrograde manner from the bladder up one or both ureters during micturition. The risk of scarring increases substantially when bacteria are flushed into the kidneys.5 Around one-third of children with a UTI will have VUR, and up to 95% of children with renal scarring may have a history of VUR.2 However, VUR occurs at varying degrees of severity, and resolves spontaneously in most children.2

The need for a guideline

Antibiotics and improvements in healthcare have changed the natural history of UTI in infants and children. This may have led to an improved outcome, but has also contributed to the current uncertainty about its management.1

The relationship between UTIs, VUR, and scarring, and the belief that prophylactic interventions are successful, has significantly influenced previous management strategies.

Making a diagnosis is particularly difficult in those most at risk, that is in young children and infants.2 Clinical presentation is often with non-specific clinical signs such as fever, irritability, and vomiting, which are also commonly seen in many acute, self-limiting childhood viral illnesses.2,6

Laboratory confirmation of the diagnosis requires the collection of an uncontaminated urine sample, which is a challenging procedure in infants and children who are yet to be toilet trained.2 Failure to consider a diagnosis of urine infection, or a delay with initiating antibiotic treatment can lead to acute clinical deterioration, and, occasionally, long-term renal damage.2

Prior to publication of the guideline from NICE, management of UTIs was based on consensus guidance published by the Royal College of Physicians (RCP) in 1991.7 Many children undergo imaging, such as ultrasound scan, micturating cystourethrogram (MCUG), or dimercaptosuccinic acid scintigraphy (DMSA), some have prolonged prophylaxis, and a few receive extensive follow up even if most of them will have neither significant pathology nor recurrence of infection. This places a heavy burden on NHS resources2 and is not without risk, for example from:

  • radiation resulting from MCUG and DMSA
  • infection after invasive imaging.

These procedures also result in undue anxiety for the parents of children with little or no chance of complications. On the other hand, a small subgroup of children appears at risk of significant morbidity either in the form of obstruction or severe bilateral renal damage.2

One aim of the NICE guideline, therefore, is to aid development of clinical pathways that will help to distinguish this small but important subgroup of children from the many children presenting with UTIs who will recover with no residual ill health.

The evidence base

Recommendations from NICE are based on systematic reviews of the best available clinical and cost-effective evidence. When minimal evidence is available, a range of consensus techniques is used to develop the recommendations.

Management decisions have often been based on estimations of complication rates. Although high-quality studies on treatment regimens, both medical and surgical, have been published in recent years, the quality of evidence on risk is generally poor.

A further difficulty for the guideline development group is that children with UTIs present in different ways at different ages, and have different predispositions and prognoses. There is also no universal agreement on how to stratify the risks to children according to their age, and there is a great deal of variation in how evidence is presented.

Diagnosis

This guideline should be viewed alongside the NICE guideline on feverish illness in children,6 also published in 2007, because younger children often present with fever, many with no obvious cause. This is a common problem, and while epidemiological information from primary care is sparse, we do know that approximately 5% of unexplained fever in children attending secondary care, or immediate care facilities, is the result of UTI.2

The NICE guideline stresses the importance of considering a diagnosis of UTI when a child has an unexplained fever. Although this was included in the 1991 RCP guideline, relatively little emphasis was placed on improving the diagnosis of UTIs in infancy and early childhood in primary care,7 even though most cases present in that age group when urine collection is particularly difficult. As a result, in the UK, the diagnosis of UTIs in primary care has not noticeably improved in pre-toilet-trained infants and children.

A number of studies, from the UK and elsewhere were assessed by the guideline development group, which provide both direct and indirect evidence that diagnostic rates are highly dependent on awareness, and are improved by active implementation of relevant guidance.2

Better detection rates of UTIs are thought to be associated with a significant drop in the number of patients reaching end-stage renal failure as a consequence of acquired renal scarring.2,3

Signs and symptoms

Table 1 lists presenting signs and symptoms for infants and children with UTI.1

Under the age of 3 months, fever, vomiting, lethargy, or irritability are the most common presentations of UTIs. In older pre-verbal children, fever is the only common presentation. Verbal children present similarly to adults, with dysuria and frequency.1

A number of predisposing factors should be noted in the patient’s record. As well as a previously recorded UTI or symptoms suggesting an unproven UTI, the more common risk factors are:

  • a family history of VUR or renal problems
  • constipation and/or dysfunctional voiding
  • poor growth.1

Table 1: Presenting signs and symptoms in infants and children with UTI

Age group Symptoms and signs
Most common ------------------------------->Least common
Infants younger than 3 months Fever

Vomiting

Lethargy

Irritability

Poor feeding

Failure to thrive

Abdominal pain

Jaundice

Haematuria

Offensive urine

Infants and children, 3 months or older Preverbal Fever Abdominal pain

Loin tenderness

Vomiting

Poor feeding

Lethargy

Irritability

Haematuria

Offensive urine

Failure to thrive

  Verbal Frequency

Dysuria

Dysfunctional voiding

Changes to continence

Abdominal pain

Loin tenderness

Fever

Malaise

Vomiting

Haematuria

Offensive urine

Cloudy urine
UTI=urinary tract infection
National Institute for Health and Care Excellence (NICE) (2007) CG54. Urinary tract infection in children: diagnosis, treatment and long-term management. London: NICE. Available from www.nice.org.uk. Reproduced with permission.

Urine collection

Clean-catch collection of urine has much lower contamination rates than the alternatives. Unfortunately, young children do not urinate to order and the clean-catch method can be messy: unsurprisingly, parents do not rate it highly. Pads provide more accurate results than bags and are usually quite acceptable. They must be checked very frequently to ensure a good sample. For primary care there is a trade-off: clean-catch is accurate but pads may provide a quicker sample. The guideline from NICE says cotton wool, gauze, and sanitary towels should not be used.1 The evidence for well-washed (with soapy water) potties8 was insufficient for the guideline development group to reach a conclusion on their merits.

Initial investigation

Culture of the urine is recommended for most, but no longer all, children. Patients over 3 years of age who have no evidence of upper UTI can be managed on the basis of a dipstick result. Dipsticks, however, are less reliable in children aged under 3 years. Instead NICE recommends the use of microscopy to make an initial diagnosis prior to confirmation by culture results.1 Few primary healthcare professionals carry this out themselves, and laboratory services are unlikely to provide this test urgently at present. Until service provision catches up with the recommendations in the guideline, the less perfect dipstick test and increased clinical suspicion, may have to suffice.

The guideline from NICE highlights the fact that children without signs and symptoms of systemic infection are not thought to be at risk of renal damage.1 A fever of 38°C or above appears, at present, to be as accurate a marker of serious infection as any other. The level of C-reactive protein is slow to rise, and while it is available as a near-patient test, it is unlikely to be sufficiently sensitive for primary care use.2 Future studies will examine the utility of sophisticated markers of disease, but these are likely to be more relevant to secondary care.

Treatment

Antibiotics

It has been customary for children to receive longer courses of antibiotics than adults, and although the standard length of treatment has reduced for both groups, there remains a disparity. Good quality evidence, as drawn on for the NICE guideline, has recently challenged this approach:

  • children will still receive longer courses of treatment, but in future this will merely reflect differences in disease presentation—they suffer higher rates of, and greater severity of, upper UTI than adults
  • children aged over 3 months who have cystitis/lower UTI require only 3 days of treatment
  • intravenous antibiotics are only necessary when oral treatment cannot be tolerated, or in very severe infections.1

Most children will be treated for possible UTI, but overall antibiotic use may not increase markedly thanks to more efficient treatment regimens.

Imaging

The use of imaging has been hotly debated.9

Children with a ‘typical’ non-recurrent UTI (for example resulting from Escherichia coli infection and an illness of lesser severity) respond quickly to treatment, and this suggests the need for a less aggressive approach to imaging in children of all ages. Recurrence is defined as two or more episodes of pyelonephritis, or three episodes of cystitis.1 Clinicians must remain vigilant to clues suggesting increased risk, so that appropriate imaging is used to the best advantage.

Prophylaxis

Children at high risk of recurrence or complications will still be managed in the same way as before, with prophylaxis being given before imaging, and on a regular basis in the case of abnormalities, however, the NICE guideline no longer advocates routine prophylaxis.1 Instead, it encourages parents and practitioners to identify recurrences and treat them promptly. Prophylaxis prior to imaging will become less common, and it is likely that this will be restricted to children whose initial infection has been more severe, more difficult to treat, or which has occurred at a very young age. Decisions on prophylaxis will be made by consultants on a case-by-case basis.

Surgery

In the 1990s, large multi-centre trials, as mentioned in the NICE guideline, showed that surgery did not improve outcomes in children with anything but the most severe VUR—any benefits were negated by post-surgical complications.Therefore the NICE guideline states that the surgical management of VUR is not routinely recommended.

Long-term follow up

If the recommendations in the guideline are observed, the burden of follow up will be reduced. Those groups affected are:

  • infants and children who have bilateral renal abnormalities, impaired kidney function, raised blood pressure, and/or proteinuria— they will still need close monitoring and careful management to slow the progression of chronic kidney disease1
  • children with minor unilateral scars—who only require follow up if they have recurrent UTI, family history, or lifestyle risk factors for hypertension
  • children without scarring at initial presentation—these patients are not followed up, but their subsequent clinical course may suggest the need for re-investigation.

Patient information

As well as general information about the treatment, investigation, and management of UTI, information should be given to parents (and older children), which will help them to spot recurrent UTI allowing prompt treatment.

Summary

Maximising the recognition of UTIs, and promptly treating all infants and children who have a probable positive diagnosis, appears, from the available evidence, to be a more effective strategy than extensively investigating all children after recovery from treatment of UTI. The guideline from NICE endeavours to correct the previous over-investigation, while maintaining adequate treatment, investigation, and follow up of high-risk children.

NICE implementation tools

NICE has developed the following tools to support implementation of its guideline on the management of urinary tract infections in children:

Implementation advice

The implementation advice document contains suggested actions for implementing the guideline. It aims to help implementers identify recommendations in the guideline that are not part of current practice, and should be used alongside the costing report and template.

Slide set

The slides are aimed at supporting organisations to raise awareness of the guideline at a local level and can be edited to cater for local audiences. They do not cover all the recommendations from the guideline but contain key messages, and should be used in conjunction with the Quick Reference Guide.

Costing tools

National cost reports and local cost templates for the guideline have also been produced.

Costing reports are estimates of the national cost impact arising from implementation based on assumptions about current practice, and predictions of how it might change following implementation of the guideline.

Costing templates are spreadsheets that allow individual NHS organisations and local health economies to estimate the costs of implementation taking into account local variation from the national estimates, and they quickly assess the impact the guideline may have on local budgets.

Audit criteria

The audit criteria and audit reporting template have been developed to assist NHS trusts to determine whether the service is implementing, and is in compliance with, the clinical guideline. Users can cut and paste the criteria into their own programmes or they can use the template provided.

These tools are available to download from the NICE website:www.nice.org.uk.

  • Urinary tract infection is a frequent cause of hospital attendance and admission for children
  • The diagnosis is often delayed in primary care
  • Children under 3 months of age with suspected UTI should be referred immediately to hospital
  • Effective diagnosis and treatment of UTIs is more important in reducing renal complications than investigation and follow up of non-recurrent and typical UTIs
  • NICE recommends that referral to paediatric specialists and imaging are unnecessary for children over 6 months old with a single typical UTI that responds well to treatment within 48 hours
  • Tariff prices:a
      • UTI acute admission = £1118
      • paediatric outpatient = £241 first visit, £121 follow up
  1. National Institute for Health and Care Excellence. Urinary tract infection in children: diagnosis, treatment and long-term management. Clinical guideline 54. London: NICE, 2007.
  2. National Collaborating Centre for Women’s and Children’s Health. Urinary tract infection in children: diagnosis, treatment and long-term management. London: Royal College of Obstetricians and Gynaecologists, 2007.
  3. Jakobsson B, Esbjorner E, Hansson S. Minimum incidence and diagnostic rate of first urinary tract infection. Pediatrics 1999; 104 (2, part 1): 222–226.
  4. Craig J. Urinary tract infection: new perspectives on a common disease. Curr Opin Infect Dis 2001; 14 (3): 309–313.
  5. Ransley P, Ridson R. Reflux and renal scarring. Br J Radiol 1978; S14: 1–35.
  6. National Institute for Health and Care Excellence. Feverish illness in children—assessment and initial management in children younger than 5 years. Quick reference guide. Clinical Guideline 47. London: NICE, 2007.
  7. Guidelines for the management of acute urinary tract infection in childhood. Report of a Working Group of the Research Unit, Royal College of Physicians. J R Coll Physicians Lond 1991; 25 (1): 36–42.
  8. Rees J, Vernon S, Pedler S, Coulthard M. Collection of urine from washed-up potties. Lancet 1996; 348 (9021):197.
  9. Mori R, Lakhanpaul M, Verrier-Kones K. Diagnosis and management of urinary tract infection in children: summary of NICE guidance. Br Med J 2007; 335 (7616): 395–397.G