Urinary tract infections (UTIs) are not uncommon in children, with some studies reporting an incidence of 2% in boys and 8% in girls under age 7. In the setting of vesicoureteral reflux (VUR), the risk of febrile UTI and recurrence of infections is heightened, which can result in long-term complications including renal scarring and chronic kidney disease.
One of the biggest challenges for pediatric nephrologists is deciding which patients are at risk for recurrence of UTIs and who may benefit from antimicrobial prophylaxis. Older studies have advocated for the use of VCUG to detect VUR in children after UTIs, as this is a known risk factor, but even children without reflux may be at risk for recurrence including those with other abnormal urinary tract anatomy or those who have bladder-bowel dysfunction. The PRIVENT trial randomized 576 children with a history of at least one prior UTI to receive trimethoprim–sulfamethoxazole or placebo and found an absolute risk reduction of 6% in the antibiotic group for recurrence of UTI during the 12-month study period. The two arms were comparable in baseline demographics and included children who had no VUR as well as varying degrees of VUR. This trial was much larger than older randomized studies from the 1970s, which also had fewer subjects with VUR.
So if antibiotic prophylaxis has a modest reduction in preventing UTIs in all-comers, how effective is it in children with known VUR? In the RIVUR study, 607 children with VUR identified after their first or second febrile or symptomatic UTI were randomized to trimethoprim–sulfamethoxazole or placebo and followed over a 2-year period. Antimicrobial prophylaxis decreased the risk of UTI recurrence (25.5% in treatment group vs. 37.4% in placebo group), with a number to treat of 8 children over the 2-year period to prevent one UTI. There was no significant difference between arms on level of adherence to providing the study medication. Prophylaxis was most effective in children with a febrile UTI as the index infection or who had concurrent bladder-bowel dysfunction. Risk of developing antimicrobial resistance was higher in the prophylaxis group (27.6% vs. 19.5%) though not statistically significant. The investigators also looked at whether antimicrobial prophylaxis could reduce the risk of worsening renal scarring or formation of new renal scars. Though they found no difference between groups, the study was not powered to detect statistical significance for this secondary outcome.
New evidence from these larger clinical trials support a role for antimicrobial prophylaxis in preventing recurrence of UTIs, particularly in high-risk patients such as those with VUR, and argues for a change in how to approach renal imaging in children with first-time UTIs. The 2011 AAP UTI clinical practice guidelines, based on a literature review performed at that time, argued that there was not enough trial data to support routine antimicrobial prophylaxis and thus prior guidance that recommended VCUG for first-time febrile UTI was not warranted; renal and bladder ultrasound was recommended, with VCUG in follow-up if ultrasound findings were concerning for VUR. This has led to some controversy, especially with the more recent RIVUR trial data supporting a role for antibiotic prophylaxis in VUR. A follow-up study looking at a historical cohort who had imaging prior to when these guidelines were published showed that the AAP guidelines would miss 56% of children in the cohort with grade 2 or higher VUR and all children with renal scarring who had a first-time febrile UTI. Despite these studies, the AAP reaffirmed its guidance in 2016, citing the benefits of cost reduction as well as decreasing patient discomfort and radiation exposure that goes along with VCUG. Though radionuclide cystogram (RNC), which has much lower radiation exposure, can be used to follow known VUR that has been diagnosed by VCUG, it doesn't provide the same level of anatomic detail for grading.
Additional large-scale trials are needed to determine whether antimicrobial prophylaxis, by way of decreasing UTI recurrence, can lower the risk of new renal scarring in children with VUR.