Pediatric Urinary Tract Infection: Diagnostic and Treatment Challenges

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Symptoms in children younger than 2 to 3 years are often nonspecific and may occur in the setting of fever of unknown etiology.
Symptoms in children younger than 2 to 3 years are often nonspecific and may occur in the setting of fever of unknown etiology.

Although UTI is the most common bacterial infection in children younger than 2 years,1 diagnosing and managing this condition can be challenging. Guidelines from myriad societies across North America and Europe offer varying levels of evidence and recommendations, contributing to this difficulty.1

Infectious Disease Advisor spoke with Alan Schroeder, MD, associate professor of hospital medicine and critical care and associate chief for research in the division of pediatric hospital medicine at the Lucile Packard Children's Hospital at Stanford in Palo Alto, California, and Joan Robinson, MD, professor of pediatrics and divisional director of pediatric infectious diseases at Faculty of Medicine and Dentistry at the University of Alberta, in Edmonton, Alberta, Canada. Dr Schroeder spoke about imaging modalities and whether there are consequences for delayed initiation of treatment. Dr Robinson discussed the consequences of overusing antibiotics and antibiotic route of administration.

Challenges in Diagnosis

Symptoms in children younger than 2 to 3 years are often nonspecific and may occur in the setting of fever of unknown etiology.1 An inherent challenge in diagnosis occurs with children who are not toilet trained. Guidelines differ on the recommended method for obtaining urine; bladder catheterization is recommended by the American Academy of Pediatrics (AAP). Other guidelines recommend either clean catch midstream void or bladder catheterization.1 The recommended capture method may differ depending on whether the sample is to be used for urinalysis or urine culture. Urinalysis is not recommended for all patients because the level of false-negative results increases when the bladder is emptied frequently or if bacteria are Gram-positive.2 The definition of a significant level of bacteriuria in a urine culture varies, which may result in a missed diagnosis if a guideline proposing a higher level is followed.1 An analysis of existing guidelines suggesting a lower level (≥103 to 105 CFU/mL with catheterization, and with clean voided urine, >104 CFU/mL with symptoms or >105 without symptoms) proposed  by the European Association of Urology and the European Society for Pediatric Urology (EAU/ESPU) may be the most appropriate guide.1

“It is important not to overdiagnose UTIs as we know that overuse of antibiotics increases cost, leads to antibiotic resistance,3 and alters the microbiome of the patient,” according to Dr Robinson. Children with febrile UTI may require additional diagnostic procedures to ensure a correct diagnosis. Voiding cystourethrogram (VCUG) and dimercaptosuccinic acid (DMSA) scintigraphy are the primary methods to identify congenital anomalies of the kidney and urinary tract (CAKUT).1 VCUG can be used to visualize the urethra and bladder and is the primary method to assess for vesicoureteral reflux (VUR). Negative consequences of missing VUR have not been firmly established, and several studies have demonstrated that mild or moderate VUR does not increase the risk of either renal scarring or recurrent UTI.1,4 Furthermore, prophylactic antibiotics do not affect renal scarring, nor are they significantly effective in preventing further UTI.5 Dr Schroeder states that “the fact that a VCUG is costly, invasive, and imparts radiation,1 and the fact that the benefit of detection of VUR remains unclear all dampen my enthusiasm for this test.”

A DMSA scan, though it can detect acute pyelonephritis and renal scarring, likely does not affect immediate clinical management and has several downsides, including cost and exposure to radiation.1 DMSA scans are generally limited to children instead of adults.6 Taking into account the variations in guideline recommendations, a recent analysis proposed that VCUG should be performed in those with recurrent febrile UTI, abnormal ultrasound, or other CAKUT risk factors, and all children should undergo a DMSA scan if they are at high risk for renal scarring, recurrent pyelonephritis, or VUR stages III to V.1

Studies have demonstrated a small increase in the risk of renal scarring if treatment is delayed by ≥3 days.7 However, systematic literature reviews and a meta-analysis have demonstrated that there is no association between treatment delay in febrile children and renal scarring.8,9 Dr Schroeder notes that “the downside of an aggressive approach toward immediate diagnosis is that this approach will be associated with a lot of catheterizations and increased costs.”

 

Challenges in Treatment

“Provided the right drug is given in the right dose, an oral route of administration works as well as intravenous administration,” stated Dr Robinson.10 All guidelines state that parenteral treatment should be used in children who are unable to eat and/or in poor general health. The National Institute for Health and Care Excellence (NICE) 2007, Polish Society of Pediatric Nephrology (PSPN) 2015, and EAU/ESPU 2016 guidelines also recommend parenteral administration in children younger than 2 or 3 months.1 Some challenges with management of pediatric UTI remain, partially due to a dearth of data to establish appropriate treatment duration.11 However, guidelines agree that there should be a minimum duration of 7 days for treatment of upper UTI and a minimum duration of 2 to 3 days for lower UTI.12 The AAP states that antibiotics excreted in the urine should not be used.1

Studies of prophylactic treatment with antimicrobial agents in children with grades I to III VUR have not demonstrated any benefit, and low-grade VUR typically resolves on its own.5,12 However, the RIVUR trial (ClinicalTrials.gov Identifier: NCT00405704) demonstrated that prophylactic treatment did reduce the risk of recurrent UTI but not renal scarring in children with VUR.13 In contrast, a Swedish study demonstrated that prophylactic treatment is effective in preventing renal scarring in girls with grade III or IV VUR.14 These studies utilized different treatments, some included only children with VUR whereas others included children both with and without VUR, and different imaging modalities were used. Evidence is mounting that complications are seen primarily in children with renal abnormalities vs those without abnormalities.9

Conclusion

Clinicians should be aware of the challenges associated with diagnosing and managing pediatric UTI. Despite these challenges, guidelines have established some general recommendations: oral therapies are advised, though parenteral administration is recommended in select cases; there is a minimum duration of 7 days' treatment for upper UTI; use of a DMSA scan and VCUG should be determined by risk factors, VUR severity, and recurrent UTI; urine collection method affects minimal level of bacteriuria for diagnosis; and a lower level of bacteriuria should be used as the standard for diagnosis.

References

  1. Okarska-Napierała M, Wasilewska A, Kuchar E. Urinary tract infection in children: diagnosis, treatment, imaging - comparison of current guidelines [published online September 19, 2017]. J Pediatr Urol. doi: 10.1016/j.jpurol.2017.07.018
  2. Whiting P, Westwood M, Watt I, Cooper J, Kleijnen J. Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review. BMC Pediatr. 2005;5:4.
  3. Kutasy B, Coyle D, Fossum M. Urinary tract infection in children: management in the era of antibiotic resistance-a pediatric urologist's view. Eur Urol Focus. 2017;3:207-211.
  4. Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A, Young L. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics. 2006;117:626-632.
  5. Montini G, Zucchetta P, Tomasi L, et al. Value of imaging studies after a first febrile urinary tract infection in young children: data from Italian renal infection study 1. Pediatrics. 2009;123:e239-e246.
  6. Browne RFJ, Zwirewich C, Torreggiani WC. Imaging of urinary tract infection in the adult. Eur Radiol. 2004;14 Suppl 3:E168-E183.
  7. Shaikh N, Mattoo TK, Keren R, et al. Early antibiotic treatment for pediatric febrile urinary tract infection and renal scarring. JAMA Pediatr. 2016;170:848-854.
  8. Hewitt IK, Pennesi M, Morello W, Ronfani L, Montini G. Antibiotic prophylaxis for urinary tract infection-related renal scarring: a systematic review. Pediatrics. 2017;139(5).
  9. Newman DH, Shreves AE, Runde DP. Pediatric urinary tract infection: does the evidence support aggressively pursuing the diagnosis? Ann Emerg Med. 2013;61:559-565.
  10. Hoberman A, Wald ER, Hickey RW, et al. Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics. 1999;104(1 Pt 1):79-86.
  11. Strohmeier Y, Hodson EM, Willis NS, Webster AC, Craig JC. Antibiotics for acute pyelonephritis in children. Cochrane Database Syst Rev. 2014;(7):CD003772.
  12. Roussey-Kesler G, Gadjos V, Idres N, et al. Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. J Urol. 2008;179(2):674-679.
  13. RIVUR Trial Investigators, Hoberman A, Greenfield SP, et al. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med. 2014;370(25):2367-2376.
  14. Brandström P, Jodal U, Sillén U, Hansson S. The Swedish reflux trial: review of a randomized, controlled trial in children with dilating vesicoureteral reflux. J Pediatr Urol. 2011;7:594-600.

 

 

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