UTI whizzdom – the next steps

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A 4-month-old baby presents with a temperature and urine microscopy suggestive of a urinary tract infection. He appears well and your plan is to discharge home on an oral antibiotic, whilst awaiting culture results. His mother asks you, “Does he need any other tests?”

Why does it matter?

Urinary tract infections (UTIs) are very common in children. Studies suggest that 6-8% of febrile, unwell children presenting to their GP have a UTI. Therefore it is important to carefully select which of these children need further investigations in order to identify those with underlying renal tract problems. It is estimated that up to 15% of children with a first UTI have evidence of scarring on follow up scans. If they are missed, these children may go on to develop hypertension and possible chronic kidney disease later in life.

Which children are more likely to get a UTI?

Before the age of 6 months, UTIs are more prevalent in boys. This is partly due to the increased chance of structural abnormalities within the urinary tract. Uncircumcised boys are particularly at risk, as bacteria on the foreskin are a reservoir for infection.

However, after 6 months of age, girls are at increased risk due to their shorter urethra and its proximity to the anus. This risk is increased again in females when they become sexually active.

Risk factors for UTIs

There are several other risk factors that increase the risk of developing a urinary tract infection. The main risk factor is something we see and manage on a daily basis, another really common presentation…constipation! If you haven’t yet read Chris Dadnam’s Conversations about Constipation post, now would be a great time to have a refresher as these two conditions go hand in hand.

As the colon and rectum fill with stool, the mass effect results in incomplete bladder emptying. This results in stasis of urine. Always ask about, and treat, constipation… If this is left unmanaged UTIs will continue to be a problem. 

After taking a good constipation history and examining the abdomen, it’s important you assess the spine looking for dimples, swellings, birthmarks or hairy patch lesions that can be associated with a neuropathic bladder. This should be followed by a lower limb neurological assessment. I think of this as running a bath after a hard day at work. You are unable to fully empty the tub afterwards but continue to add more bathwater to the tub every time… this will encourage infection to harbour. Recurrent UTIs may be the main presenting complaint in young children and should always prompt a review of the spine.

Foreign bodies such as intermittent or indwelling catheters also pose a risk. But it is essential to remember the last risk factor, not visible to the eye … namely urinary reflux.

Is this the same as vesico-ureteric reflux?

Yes. This is simply a term describing where, anatomically, the reflux occurs – from the bladder (vesico) to the ureters (ureteric). Urine flows back up from the bladder to the ureters causing a bidirectional flow of urine.

VUR can be primary, i.e. within a normal renal tract, or secondary, due to an abnormal renal tract – such as a neuropathic bladder. It is graded from 1 (mild) to 5 (severe.) Most mild to moderate reflux resolves by 5 years of age. However, surgery may be indicated if severe reflux is present, with worsening renal impairment or frequent pyelonephritis.

History and examination

As part of the history taking and examination, it is key to think about whether there could be underlying constipation, VUR or a neuropathic bladder. Asking about a family history of renal problems as well as considering antenatal renal scans is important to risk stratify for structural problems.

Ask about

  1. Constipation
  2. Urine flow
  3. Lower limb/back problems
  4. Antenatal renal abnormalities
  5. Family history of renal problems
  6. History of previous UTI/ fevers

Examine for

  1. Hypertension (complication)
  2. Poor growth
  3. Spine – for any spinal lesions
  4. Lower limb neurology
  5. Faecal masses
  6. Enlarged bladder / abdominal mass

What do we need to consider when further investigating UTIs?

NICE (the National Institute for Health and Care Excellence) ask the following three questions when considering a child’s risk of reflux and scarring:

How old is the child? Age is important. This may be a neonate or infant presenting with an infection as the first indicator of a possible underlying structural abnormality such as posterior urethral valves or VUR.

Is this an atypical UTI? 80% of paediatric UTIs are secondary to E.coli infection. An infection caused by an organism other than E.coli, or not responding within 48 hours of antibiotic therapy, is more unusual. Equally, if a child with a UTI looks unwell, has a palpable bladder, renal impairment or poor urine flow, your index of suspicion should be raised. These are uncharacteristic signs of a urinary tract infection.

Is this child having recurrent infections? Over 30% of children with UTIs will suffer from recurrent infections. Recurrent infections are defined as children who have either 2 or more upper UTIs (affecting the kidneys or ureters), 3 lower urinary tract infections (affecting the bladder or urethra) or 1 upper and 1 lower infection at any point up until the age of 16.

Investigations? Clear as M.U.D.

  • MCUG in 4 – 6 months
  • Ultrasound scan acutely or within 6 weeks
  • DMSA in 4 – 6 months

MCUG

An MCUG is a Micturating Cystourethrogram, which assesses for urinary reflux or obstruction. A catheter is inserted and radio-opaque contrast is administered via the catheter to fill up the bladder. X-rays are then taken during urination to see if urine is refluxing back towards the kidney.

Normal MCUG. Case courtesy of Dr Aditya Shetty, Radiopaedia.org. From the case rID: 27065
MCUG illustrating marked dilatation of the prostatic portion of the urethra consistent with posterior urethral valves. Case courtesy of Dr Andrew Dixon, Radiopaedia.org. From the case rID: 10432

DMSA

A DMSA scan is used to assess the function and location of the kidneys. An isotope that emits gamma rays is attached to ‘Dimercaptosuccinic acid’. This is administered via an intravenous cannula and is taken up by the kidneys a few hours later. If performed acutely it can show altered function consistent with pyelonephritis. In the UK, a DMSA scan is undertaken 4-6 months post-infection to assess for scarring.                       

A normal DMSA with equal isotope uptake in both kidneys. Case courtesy of Dr Yusra Sheikh, Radiopaedia.org. From the case rID: 69041

What does the guidance say?

In 2007, NICE published a guideline called “Urinary tract infection in the under 16s: diagnosis and management”, updated in 2018. When it comes to imaging, there are three main highlights.

1. Children under 6 months of age with a first typical UTI should have an ultrasound to assess for a structural cause. An MCUG is considered if this is abnormal.

2. All children with an atypical UTI, regardless of age, should have an ultrasound acutely. A DMSA is also performed if they are under 3 years of age to assess renal parenchyma. Children under 6 months are investigated more fully with an USS, DMSA and MCUG.

3. All recurrent UTIs require a DMSA scan within 4-6 months to assess for scarring.

This traditional approach for investigating children for reflux and scarring is safe yet adopts a different approach to imaging children with UTIs compared with other countries.

Controversial whizzarding….

The decision of who should be investigated further has caused great controversy. Different approaches are adopted around the world. This is due to conflicting evidence with clinicians balancing the risk of radiation, invasive imaging and cost with that of detecting children with an underlying congenital anomaly and preventing the development of chronic kidney disease.

There is conflicting data surrounding the risk factors for VUR in children with their first UTI. Ristola et al (2017) investigated risk factors for children with UTIs, finding the following 3 as the main risk factors for reflux: ultrasound abnormalities, recurrent infections and atypical infections. Interestingly, non-E. coli infections were the only statistically significant risk factor of infection recurrence.

Yılmaz et al (2016) were unable to identify risk factors associated with VUR, although did note that an abnormal renal scan at 6 months after the infection was closely related to the presence of VUR and recurrent UTIs.

In America, Canada, Poland and Italy, children up to 2 -3 years of age with their first UTI would be advised to have an ultrasound. The European Association of Urology advises every child presenting with a first UTI to be investigated with sonography. This is in comparison with the 6 month cut off advised by NICE, which is argued to be a more cost effective and risk stratified approach.

However, the American, Canadian and Italian guidelines do not investigate all children with recurrent UTIs as previously advised by the NICE guidance. Instead of all children with recurrent UTIs undergoing a DMSA scan, recent guidance suggests only performing a DMSA if there were concerns regarding an abnormal ultrasound or alternative diagnosis.

Therefore this makes me wonder, instead of investigating all children with recurrent UTIs, perhaps this decision should be made on an individual basis, using their ultrasound findings and considering risk factors.

How accurate are ultrasound scans in picking up VUR?

An ultrasound cannot exclude all cases of VUR as it is an observer-dependent investigation. Mahant et al (2002) reported low sensitivity of 40% and a specificity of 76% when diagnosing VUR, but the majority of these patients had lower grade reflux. There is now increasing awareness that low-grade reflux and mild scarring are unlikely to cause long term problems, therefore the argument presents itself: is there any benefit in investigating for them? Ultrasound scans are more likely to detect higher grade reflux and hence clinically significant cases, but further evidence is needed to support this approach.

The take homes

Some evidence suggests that children with ultrasound abnormalities or recurrent UTIS are at increased risk of complications from UTIs, regardless of their age or sex. There is no clear consensus on when to request a DMSA or MCUG but the latest evidence suggests that DMSA scans may not be necessary in all children with recurrent infections and a normal ultrasound scan. Clinicians should be aware of this existing controversy, weighing up the benefits and risks in order to make informed clinical decisions.

References

Craig J. Urinary tract infection: new perspectives on a common disease. Curr Opin Infect Dis 2001; 14 (3): 309–313.

Davis A, Obi B, Ingram M. Investigating Urinary tract infections in children BMJ 2013; 346 : e8654

Edlin RS, Shapiro DJ, Hersh AL, et al Antibiotic resistance patterns of outpatient pediatric urinary tract infections. J Urol2013;190:222–7.doi:10.1016/j.juro.2013.01.069

Kaufman J, Temple-Smith M, Sanci LUrinary tract infections in children: an overview of diagnosis and management BMJ Paediatrics Open 2019;3:e000487. doi: 10.1136/bmjpo-2019-000487

Mahant S, Friedman J, MacArthur C. Renal ultrasound findings and vesicoureteral reflux in children hospitalised with urinary tract infection. Arch Dis Child. 2002 Jun;86(6):419-20. doi: 10.1136/adc.86.6.419. PMID: 12023172; PMCID: PMC1762998.

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

National Institute for Health and Care Excellence. Urinary tract infection in children: diagnosis, treatment and long-term management. Clinical guideline 54. London: NICE, 2007.

Newman DH, Shreves AE, Runde DP Pediatric urinary tract infection: does the evidence support aggressively pursuing the diagnosis?Ann Emerg Med2013;61:559–65.doi:10.1016/j.annemergmed.2012.10.034

O’Brien K, Edwards A, Hood K, et al Prevalence of urinary tract infection in acutely unwell children in general practice: a prospective study with systematic urine sampling. Br J Gen Pract2013;63:e156–64. doi:10.3399/bjgp13X663127

Okarska-Napierała M, Wasilewska A, Kuchar E Urinary tract infection in children: Diagnosis, treatment, imaging – Comparison of current guidelines. J Pediatr Urol2017;13:567–73.doi:10.1016/j.jpurol.2017.07.018

Ristola MT, Löyttyniemi E, Hurme T. Factors Associated with Abnormal Imaging and Infection Recurrence after a First Febrile Urinary Tract Infection in Children. Eur J Pediatr Surg. 2017 Apr;27(2):142-149. doi: 10.1055/s-0036-1572418. Epub 2016 Feb 8. PMID: 26855368.

Shaikh N, Craig JC, Rovers MM, et al. Identification of children and adolescents at risk for renal scarring after a first urinary tract infection: a meta-analysis with individual patient data. JAMA Pediatr2014;168:893–900.doi:10.1001/jamapediatrics.2014.637

Shaw KN, McGowan KL, Gorelick MH, Schwartz JS. Screening for Urinary Tract Infection in Infants in the Emergency Department: Which Test Is Best? Pediatrics. 1998;

Stein R, Dogan HS, Hoebeke P, et al Urinary tract infections in children: EAU/ESPU guidelines. Eur Urol2015;67:546–58.doi:10.1016/j.eururo.2014.11.007

Subcommittee on Urinary Tract Infection Reaffirmation of AAP clinical practice guideline: the diagnosis and management of the initial urinary tract infection in febrile infants and young children 2-24 months of age. Pediatrics 2016;138:e20163026.doi:10.1542/peds.2016-3026

Yılmaz S, Özçakar ZB, Kurt Şükür ED, Bulum B, Kavaz A, Elhan AH, Yalçınkaya F. Vesicoureteral Reflux and Renal Scarring Risk in Children after the First Febrile Urinary Tract Infection. Nephron. 2016;132(3):175-80. doi: 10.1159/000443536. Epub 2016 Feb 23. PMID: 26901769.

          

                                         

About the authors

  • Felicity is a paediatric registrar from The West Midlands, currently in Bristol working on a PG Cert in medical education. Felicity has a passion for teaching and outside of work can be found singing with the City of Birmingham Symphony Orchestra Chorus or trying to sing like Beyonce in the shower!

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