BOSTON — A recent study suggesting that prophylactic antibiotics for an initial urinary tract infection in children do not prevent recurrent infection and may, in fact, contribute to an increased risk of recurrent infection with a resistant bacteria has raised questions about the standard of care for these patients.
Dr. Ron Keren of the Children's Hospital of Philadelphia made this presentationat the annual meeting of the American Academy of Pediatrics.
The AAP 1999 practice parameter recommends that all children with a first urinary tract infection (UTI) undergo renal ultrasound to detect abnormalities such as hydronephrosis, bladder hypertrophy, and ureteroceles; and either a voiding cystourethrogram (VCUG) or direct radionuclide cystography (RNC) to evaluate the presence and degree of vesicoureteral reflux (VUR), Dr. Keren explained. Conventional wisdom has been that evidence of VUR, which is found in 30%–40% of children with UTI, warrants prophylactic antibiotic treatment to prevent recurrent infection and subsequent kidney damage, he said.
In an observational study, Dr. Keren and his colleagues reviewed the electronic health records of nearly 80,000 children with at least two pediatric care visits over a 5-year period and identified 611 children who had been diagnosed with a first UTI (JAMA 2007;298:179–86). “We then looked forward into the records to determine how many of these kids had recurrent [UTI], what the risk factors were, and whether the prescription of prophylactic antibiotics actually changed the risk,” he said.
Of those 611 children who'd had a UTI, 83 (14%) had been diagnosed with a recurrent infection. With use of a time-to-event analysis, “white children, older children, and children with high-grade VUR had a statistically significant increased risk of recurrent UTI, while having been prescribed prophylactic antibiotics had no relationship to recurrent infection,” he said, noting that children with low grade VUR, which is what the majority of kids have when there is evidence of VUR, were not at increased risk for reinfection. Additionally, “having been exposed to prophylactic antibiotics increased the odds of reinfection with a bug that was not pansensitive almost eightfold,” he said.
Multiple clinical trials also have failed to show a benefit of prophylactic antibiotics for the prevention of recurrent UTIs, and the authors of a 2006 systematic review of the available literature reported that the evidence to support the widespread use of antibiotics to prevent recurrent, symptomatic UTI is weak but stressed the need for large randomized, double-blinded clinical trials (Cochrane Database Syst. Rev. 2006; doi:10.1002/14651858.CD001534).
Given the apparent contradiction between the evidence and the standard of care, what is a pediatrician or parent to do? “Remember the old saying: 'The absence of evidence is not evidence of absence of benefit,'” Dr. Keren advised. “Right now, the AAP says we should be screening these kids, and we should probably be doing something about what we find. It's perfectly fine to take the conservative approach and continue to screen all kids for VUR after the first UTI and continue to prescribe prophylactic antibiotics for kids with VUR until the VUR resolves, until we get better evidence.”
But it's also okay to use clinical judgment with respect to individualizing care, Dr. Keren stressed. “There's a big difference between a 3-year-old girl with her first afebrile UTI concurrent with potty training vs. a 5-month-old girl with febrile UTI requiring hospitalization and a history of febrile illnesses that got better with antibiotics, and a sibling and mother with a history of dilating VUR,” he said. “These are two very different creatures. I would seriously consider screening the latter child for VUR but waiting for recurrent UTI before screening the older child.”
Interestingly, the AAP imaging recommendations as outlined in the practice parameter also have been the subject of controversy. “The guidelines were written for children from 2 to 24 months of age. There's no comment on what to do for older children, yet when you look at the epidemiology of UTI in kids, the majority of children are between 2 and 6 years old when they get their first UTI. Should we be doing the same for a 4-year-old as we do for a 2- to 24-month old?” asked Dr. Keren. And while the guidelines clearly spell out imaging recommendations, “they don't tell us what to do with the findings uncovered on imaging.”
Because of this, the current management model for VUR comes from the American Urological Association (AUA) guidelines, which indicate that treatment should be decided based the age of the child and the grade of VUR based on the International Classification System for vesicoureteral reflux. “With the exception of kids between 1 and 5 years with bilateral grade V VUR and kids 6–10 years with bilateral grade III or IV reflux or unilateral grade V reflux, for whom surgery is recommended, the AUG recommends prophylactic antibiotics for initial management of kids who don't have renal scarring at the time of diagnosis,” said Dr. Keren.