Identify and Treat Urinary Tract Infection Promptly in Under 16s

Dr David M W Capehorn Dissects NICE Guidance on Urinary Tract Infection in Children and Young People, Covering Diagnosis, Testing, and Management in Primary Care

NICE Guideline (NG) 224, Urinary tract infection in under 16s: diagnosis and management,¹ was published on 27 July 2022. It provides updated guidance on the diagnosis and management of a first or recurrent urinary tract infection (UTI) in children and young people aged up to 16 years.¹

It should be noted that NG224 does not provide guidance for those with catheters in situ, those with pre-existing uropathies, those with known underlying renal disease, and those in whom there is immunosuppression. It also does not provide guidance on recurrent UTI in sexually active young girls aged less than 16 years; the latter group needs to be considered separately, both in terms of potential sexual health issues and safeguarding implications.

UTI is relatively common in childhood, although precise figures for presentations to primary care for UTI by children and young people are unclear.² The consensus is that UTIs affect around one in 10 girls and one in 30 boys by the age of 16 years.³ In most cases, UTIs are caused by bacteria from the gastrointestinal tract and, in childhood, around 85–90% of cases involve Escherichia coli infection.⁴ As in adults, a urine infection is definitively diagnosed when a pure growth of an organism is obtained on urine culture (usually 100,000 colony-forming units per millilitre of voided urine, but local guidelines vary).^5,6

Overall, the prognosis for paediatric UTI is good; however, early diagnosis is important. Most kidney parenchymal defects are congenital, but they can be associated with UTI.⁷ Prompt treatment after obtaining urine for culture may help to reduce the risk of complications, which include sepsis, acute kidney injury and, rarely, chronic kidney disease.⁸ Other potential longer-term risks include bacteriuria and hypertension in later pregnancy, and pre-eclampsia.⁷

UTI in childhood presents various challenges for healthcare practitioners, particularly in a primary care setting. These challenges can be considered at each of the following steps of care, which will be covered in this article with reference to NG224:

1. Considering a diagnosis of UTI
2. Collecting and storing a urine sample
3. Interpreting and acting upon urine dipstick analysis and microscopy results
4. Treatment, including antibiotic prescribing
5. Consideration of follow up, preventing recurrence, and scanning criteria.

Step 1: Considering a Diagnosis of UTI

The first challenge in primary care concerns the identification of possible cases, as the signs and symptoms of UTI in childhood vary by age and are generally nonspecific, especially in babies and children aged less than 3 years.¹ Because of this uncertainty, it is important to consider alternative diagnoses when symptoms and signs are present that decrease the likelihood of UTI—for example, upper or lower respiratory symptoms, or nappy rash.¹

General Signs and Symptoms of UTI

Certain signs and symptoms should be taken seriously as indicators of UTI.¹ NICE outlines a number of signs and symptoms that either increase or decrease the likelihood of UTI (see Table 1),¹ many of which overlap with the Public Health England (PHE) quick-reference tool for primary care on UTIs, which separates them more explicitly by age.⁵ It is worth noting that some signs and symptoms identified by PHE are excluded by NICE because the Guideline Development Committee felt that there was insufficient evidence that these symptoms are useful for identifying UTIs—specifically, lethargy, irritability, poor feeding, vomiting, failure to thrive, and jaundice.^1,5 Furthermore, some symptoms, including cloudy and offensive urine, may only be assessable after a urine sample is taken.¹

Table 1: Symptoms and Signs that Increase or Decrease the Likelihood that a UTI is Present¹

NICE emphasises that the presence of multiple signs and symptoms increases the likelihood of UTI, but that the absence or presence of one or more symptoms should not exclusively determine the need to test urine.¹ Consideration also needs to be given as to whether a child is verbal.¹

More Specific Signs and Symptoms

A fever of greater than 38ºC and systemic symptoms (for example, bacteriuria, loin pain, or tenderness) may suggest upper UTI (pyelonephritis) rather than lower UTI (cystitis).^1,6

When assessing a child in whom UTI is a possibility, their medical and family history should be taken into account.¹ The following should be noted as possible risk factors for recurrent infection or as suggestive of underlying pathology:¹

• history of confirmed or suspected UTI, or recurrent fever of unknown origin
• family history of renal disease or vesicoureteral reflux (VUR)
• the presence of constipation or another abdominal problem, such as an abdominal mass
• dysfunctional voiding or poor urine flow
• a history of faltering growth
• an antenatally diagnosed renal abnormality
• the presence of other clinical findings, such as evidence of spinal lesions, high blood pressure, or an enlarged bladder.

Step 2: Collecting and Storing a Urine Sample

NICE suggests a low threshold for urine testing, recommending that a child’s urine is tested in the following circumstances:¹

• the patient has signs and symptoms that suggest UTI (see Table 1)
• the patient is unwell with none of the listed symptoms and signs of UTI, but there is still suspicion of UTI.

Dipstick testing for leukocyte esterase and nitrites is recommended for initial urine testing, but urine may need to be sent for microscopy and culture in certain circumstances (see Step 3: Interpreting and acting upon urine dipstick analysis and microscopy results).¹

In primary care, collection and storage of a urine sample often presents practical difficulties.¹ However, a delay obtaining the sample should be avoided. Therefore, if the sample cannot be collected in the consultation, NICE recommends asking the patient’s carers to return the urine sample as soon as possible, ideally within 24 hours.¹

In particular, clinicians should not delay treatment in any child at high risk of serious illness regardless of whether a urine sample can be taken, as outlined in NG143, Fever in under 5s: assessment and initial management (see Table 2).^1,9 NICE also recommends immediately referring all babies and children at high risk of serious illness to a paediatric specialist.¹

Table 2: Symptoms and Signs Suggesting High or Intermediate Risk of Serious Illness Under the Age of 5 Years⁹

Urine Collection Methods

Clean catch is the recommended method for collecting urine (potties cleaned with hot water and washing up liquid may be used).^1,5,10 If clean catch is not possible, NICE recommends using other noninvasive methods, such as commercial urine collection pads.¹ Importantly, the use of cotton wool balls, sanitary towels, gauze, or urine bags for collecting urine is advised against, because of the risk of contamination.^1,5

Storage of Urine Samples in Primary Care

Urine samples should ideally be cultured in a laboratory within 4 hours, or stored in a refrigerator at 4ºC if this is not possible;^1,5,11 a refrigerated sample remains suitable for culture for up to 48 hours, which makes this possible in primary care.¹¹ If the sample is properly preserved with boric acid, it remains suitable for culture for 96 hours, but manufacturers’ instructions must be followed, particularly concerning sample volume, and it is worth noting that boric acid may inhibit tests for leukocyte esterase in particular.¹¹

Step 3: Interpreting and Acting Upon Urine Dipstick Analysis and Microscopy Results

When interpreting urine dipstick test results, some general principles apply:

• urine dipstick testing for leukocytes and nitrites has predictive value and can safely be used for children over the age of 3 months prior to sending a sample for microscopy, culture, and sensitivity (MC&S)¹—NG224 categorises results and further actions in accordance with Box 1 and Table 3
• for children younger than 3 months old in whom UTI is suspected, NICE suggests immediate referral to secondary care, urgent MC&S urine testing, and management of the patient in line with NG143 (see Table 2).^1,9 This is because these patients are more likely to be difficult to diagnose, they may be clinically more unwell because of the immaturity of their immune system, and dipstick testing is generally less reliable in younger infants (nitrite formation may not occur, as young babies pass urine frequently)^6,12,13
• clinical criteria outweigh urine dipstick analysis when making treatment decisions.¹

Table 3: Urine Dipstick Testing Strategies for Children 3 Years or Older¹

Microscopy, Culture, and Sensitivity Testing

In primary care, immediate microscopy is often unavailable. However, if it is available, the presence of pyuria or bacteriuria should also lead to a suspicion of UTI as follows:¹

• if pyuria and bacteriuria tests are both positive, or only bacteriuria tests are positive, NICE recommends assuming the patient has a UTI and starting treatment immediately
• if pyuria tests are positive but bacteriuria tests are negative, NICE recommends starting treatment if there are clinical symptoms of UTI.

Indications for sending a urine sample for MC&S testing include:¹

• the patient has a high or intermediate risk of serious illness (see Table 2), or has symptoms of acute upper UTI (pyelonephritis)
• the patient is younger than 3 months old
• leukocyte and/or nitrite tests are positive
• the clinician has a strong suspicion of UTI despite negative dipstick test results
• the patient has a history of recurrent UTI
• the infection fails to respond to treatment after 24–48 hours.

Step 4: Treatment, Including Antibiotic Prescribing

Whenever prescribing medication to children, clinicians must consider local policies and individual patient clinical factors. Dosages should be in accordance with age and weight guidance in the British National Formulary for Children (BNFC)—bnfc.nice.org.uk.

Children Aged Under 3 Months

Refer children aged less than 3 months urgently to a paediatric specialist in secondary care for treatment.¹

Children Aged Over 3 Months

In general, NICE recommends giving antibiotics to children aged over 3 months with UTI in line with NG109, Urinary tract infection (lower): antimicrobial prescribing¹⁴ and NG111, Pyelonephritis (acute): antimicrobial prescribing.^1,15 Therefore, for children aged more than 3 months:

• with an uncomplicated lower UTI (with no evidence of pyelonephritis or systemic symptoms)—a 3-day course of antibiotics is standard^14,16
  • first-choice oral antibiotic—usually trimethoprim^14,16,17 or nitrofurantoin^14,16,18
  • second-choice oral antibiotic—nitrofurantoin (if not first choice),^14,16,18 amoxicillin (if culture results are available, and there are susceptible organisms),^16,19 or cefalexin^14,16,20
  • do not use trimethoprim if there is risk of antibiotic resistance—for example, if it has been used in the last 3 months¹⁴
  • do not use nitrofurantoin if the patient’s estimated glomerular filtration rate (eGFR) is less than 30 ml/minute/1.73 m², and use it with caution (and only where benefit outweighs risk) if their eGFR is 45 ml/minute/1.73 m² or less^14,18
• with a complicated UTI (with systemic symptoms/pyelonephritis)—a 7–10-day course of antibiotics is standard^15,16
  • oral antibiotic—cefalexin^15,16,20 or co-amoxiclav (if culture results are available, and there are susceptible organisms)^15,16,21
  • intravenous (IV) antibiotic—if the child is vomiting, severely unwell, or unable to take oral antibiotics, referral to secondary care is recommended for IV antibiotic treatment, usually consisting of co-amoxiclav, cefuroxime, ceftriaxone, gentamicin, or amikacin^15,16
  • clinicians may also consider referring those over 3 months with upper UTI to a paediatric specialist.¹

NICE also states the following principles regarding treatment choice:

• if a patient is already on prophylactic antibiotics, treatment should be with a different antibiotic^14–16
• do not treat asymptomatic bacteriuria.¹

Step 5: Consideration of Follow Up, Preventing Recurrence, and Scanning Criteria

NG224 recognises that some children no longer need extensive investigation following UTI, especially those with a first UTI who respond quickly to a course of antibiotics.¹ However, children with atypical or recurrent UTI (as defined in Box 2) may still need investigation. In principle, the extent of further investigation is determined by:¹

• the age of the child at the time of their first UTI
• whether their UTI is atypical or recurrent (see Box 2).

Patients with a First-Time UTI that Responds Well to Treatment Within 48 Hours

If the patient is aged less than 6 months with a first-time UTI that has responded well to treatment, clinicians are recommended to arrange an ultrasound scan (USS) within 6 weeks.¹ If the USS results are abnormal, clinicians should then refer the patient to secondary care for paediatric assessment—a micturating cystourethrogram (MCUG) may be required, and a dimercaptosuccinic acid (DMSA) scintigraphy scan may be needed 4–6 months after infection to assess renal scarring and relative renal function.¹

Patients aged 6 months or older with a first-time UTI who have responded well to treatment do not require investigation or follow up.¹

Atypical or Recurrent UTI

If the patient is aged less than 6 months with an atypical or recurrent UTI that is not responding well to treatment within 48 hours, clinicians should arrange a USS during the acute episode.¹ It may be advisable to refer them to secondary care, as it is likely that an MCUG will be needed, as well as a DMSA scintigraphy scan 4–6 months after the most recent UTI.¹

If the patient is aged 6 months–3 years with a UTI that is not responding well to treatment within 48 hours, NICE recommends arranging a USS during the acute episode if the UTI is atypical, and within 6 weeks of the acute episode if the UTI is recurrent.¹ The child may need a DMSA scintigraphy scan after the most recent UTI, and consideration may be given to an MCUG,¹ so referral to secondary care may be sensible.

If the UTI is not responding well to treatment within 48 hours and the patient is aged more than 3 years with:¹

• an atypical infection—a USS involving a bladder-emptying assessment should be requested during the acute infection and, if normal, no follow up will be needed. If the USS is abnormal, then referral to secondary care is advised, as assessment by a paediatric specialist is required
• a recurrent infection—a USS involving a bladder-emptying assessment should be arranged within 6 weeks of infection, and secondary care referral may again be wise because DMSA scintigraphy scanning is recommended 4–6 months after the most recent UTI.

Usually, MCUGs are considered if the patient has ureteric dilatation on a USS, poor urine flow, a non-E. coli UTI, or a family history of VUR.¹

Follow Up, Advice, and Antibiotic Prophylaxis

For follow up and prevention of recurrence, NICE also recommends the following:

• for all cases, consideration should be given to looking for and managing underlying reasons for the infection. A clinician’s role may involve providing advice to children and their parents or carers about:^1,22,23
  • not ‘holding on’ (avoiding delayed bladder voiding)
  • timed toileting and regular bladder emptying every 90–120 minutes
  • treating underlying constipation with stool softeners, where appropriate
  • if necessary, increasing fluid intake to avoid dehydration
  • ensuring careful wiping technique after passing urine
  • personal hygiene measures
• longer-term follow up is generally not needed if imaging results are normal¹
• patients with recurrent UTIs will require follow up and assessment by a paediatric specialist even if the initial imaging is normal, as will those with abnormal imaging, impaired renal function, proteinuria, or hypertension¹
• for those children with recurrent UTI for whom behavioural and personal hygiene measures alone are not effective or not appropriate, consideration may be given to antibiotic prophylaxis, after specialist advice^1,14—normally, this would consist of trimethoprim,¹⁷ nitrofurantoin,¹⁸ cefalexin,²⁰ or amoxicillin¹⁹ as a single dose at night (with dosing in line with the BNFC).

Conclusion

This new NICE guideline provides further clarity on the complex but important issue of identifying UTI in childhood. NICE has updated and streamlined its list of symptoms suggestive of UTI in under 16s. There is greater emphasis placed on urine testing where signs suggest a UTI is more likely than not, or the GP has suspicion of UTI but symptoms are absent. A significant challenge in primary care has always been the collection of a timely urine sample, and this update stresses avoiding delay in the collection and testing of urine, which—if not done in the consultation—needs to be performed within 24 hours.