Do antibiotics treat VUR?

Continuous antibiotic prophylaxis (CAP) does not treat urinary reflux

According to the American Urologic Association (AUA), the primary goal of VUR management is to prevent febrile UTIs (fUTIs), prevent renal injury and minimize follow-up and morbidity.1

Antibiotic prophylaxis does not treat VUR, rather, it is used to treat bacteria in the urine (UTIs) that can cause renal scarring. Low dose, continuous antibiotic prophylaxis (CAP) decreases the offs of UTI development in children with reflux; however, evidence is conflicting with regard to CAP and prevention of renal scarring.2

Antibiotics and the management of VUR

Preventing febrile UTIs

Real-world Analysis of VUR Management With Continuous Antibiotic Prophylaxis (CAP) Therapy3

  • >35,000 patients with VUR
  • 76.5% were treated with initial CAP therapy
  • Only 17% were adherent
  • 58% experienced UTI recurrence within 1 year of starting CAP therapy
  • 63.8% of patients complying 100% still had evidence of a UTI diagnosis

Conclusion: Only 17% of paediatric VUR patients on CAP were compliant with therapy. Of patients on CAP therapy, 58% had a diagnosis of a UTI within 1 year of treatment.

In another 1-year, follow-up, randomized urinary antibiotic prophylaxis-controlled study, the rate of fUTIs was higher with antibiotic prophylaxis than with no treatment at all (N=218):4

  • 12.9% of VUR patients had fUTI recurrence with continuous antibiotic prophylaxis
  • 1.7% of VUR patients had fUTI recurrence with no prophylaxis
  • The study suggested that the prophylaxis rate is more likely due to poor compliance and the development of antibiotic resistance

Conclusion: Continuous antibiotic prophylaxis did not prevent the recurrence of infection or the development of renal scars.

Preventing renal injury

The results from the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial show that antibiotic prophylaxis may not prevent kidney scarring1, a primary goal of VUR treatment.5

Effects of low-dose antibiotic prophylaxis in children

Continuous antibiotic prophylaxis has a negative impact on growth6

Seventeen epidemiologic studies suggesting that antibiotic exposure during critical periods of early development may influence weight gain and the development of obesity. Evidence to date suggest this strategy should include the judicious use of antibiotics, especially in early life when the developing guy microbiota is particularly susceptible to perturbations with long-lasting implications for metabolic programming and obesity risk.

Effects of low-dose antibiotic prophylaxis in children include:7

  • Significant increase in BMI percentile in children >1-year old
  • Associated with decreased height percentiles, particularly in patients <1-year old

VUR patients have an increased risk of multidrug resistance

Although antibiotic prophylaxis may treat UTIs, antibiotic therapy has been shown to increase antibiotic resistance. Symptomatic UTI recurrence with resistant E. coli was significantly more likely to occur among those on antibiotic prophylaxis (63%) compared with those on placebo (19%).5

A study of 1,229 patients with VUR showed:8

  • 1 multidrug-resistant infection would develop for every 21 Deflux patients treated with CAP
  • 6.4x increased odds of developing a multi-drug resistant infection for children with VUR on antibiotic prophylaxis

The World Health Organization states that antibiotic resistance is one of the biggest threats to global health, food security, and development today.

Considerations of Deflux versus antibiotics
  • Deflux offers immediate protection from further renal damage without the need for adherence to a long-term treatment regiment9

References:
  1. American Urological Association. Management and screening of primary vesicoureteral reflux in children: AUA guideline. 2010.
  2. Baskin LS, Kogan BA, Stock JA. Handbook of Pediatric Urology Third Edition. Philadelphia, PA: Wolters Kluwer; 2019.
  3. Hensle TW, Hyun G, Grogg AL, Eaddy M. Part 2: Examining pediatric vesicoureteral reflux: A real-world evaluation of treatment patterns and outcomes. Curr Med Res Opin. 2007;23(4)S7-S13. DOI: 10.1185/030079907X226221
  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(3):626-632. DOI: 10.1542/peds.2005-1362
  5. The RIVUR Trial Investigators. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med. 2014;370:2367-2376. DOI: 10.1056/NEJMoa1401811
  6. Guidos PJ, Arlen AM, Leong T, et al. Impact of continuous low-dose antibiotic prophylaxis on growth in children with vesicoureteral reflux. J Pediatr Urol. 2018;14(4):325.e1-325.e7. DOI: 10.1016/j.jpurol.2018.07.007
  7. Azad MD, Moossavi S. Owara A, Epheri S. Early-life antibiotic exposure, gut microbiota development, and predisposition to obesity. Nestle Nutr Inst Workship Ser. 2017;88:67-79. DOI:10.1159/000455216
  8. Selekman RE, Shapiro DJ, Boscardin J, et al. Uropathogen resistance and antibiotic prophylaxis: a meta-analysis. Pediatr. 2018;142(1):e020180119. DOI: 10.1542/peds.2018-0119
  9. Elder JS, Shah MB, Batiste LR, Eaddy M. Part 3: Endoscopic injection versus antibiotic prophylaxis in the reduction of urinary tract infection in patients with vesicoureteral reflux. Curr Med Res Opin. 2007;23(4):S15-20. DOI: 10.1185/030079907X226230
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