Does antibiotic resistance change over time in children on prophylaxis? A new study says yes.

biofilm of  antibiotic resistant bacteria
Biofilm of antibiotic resistant bacteria (Shutterstock)

When treating children with a history of urinary tract infections (UTIs) and reflux, pediatricians and primary care staff treat their young patients with preventative antibiotics. Although antimicrobial prophylaxis has been proven effective in preventing recurrent UTI in children specifically with vesicoureteral reflux, the question caregivers often ask is:

“Are you doing more harm than good in terms of creating resistance?” 

According to Caleb Nelson, MD, MPH director of Quality and Safety and attending urologist in the Department of Urology at Boston Children’s Hospital, this question often causes a pause or prompts reluctance to use the medication.

“From the pediatrician standpoint, it’s useful to know more about what happens when you treat these kids in terms of how the resistance patterns change – or don’t change, over time.”

Nelson, who served as lead author of the follow-up, multi-center study titled “Antimicrobial Resistance and Urinary Tract Infection Recurrence,” sought to further investigate the relationship of antibiotic use and antibiotic resistance among children with vesicoureteral reflux.

The paper, published in Pediatrics by the American Academy of Pediatrics (AAP), shows that although resistance was more common among children on antibiotic prophylaxis, antibiotic resistance decreased the longer the children stayed on prophylaxis. This surprising finding suggests that children who require extended prophylaxis may not be at as high a risk of resistant infection as commonly thought.

Notes asked Nelson a series of questions about the “Antimicrobial Resistance and Urinary Tract Infection Recurrence” study and its outcomes and impact on patient care.

Notes: What was the impetus for the “Antimicrobial Resistance and Urinary Tract Infection Recurrence” study?

Nelson: One of the findings from the primary trial was that although the preventative antibiotics do work, we were seeing more antibiotic resistance in the group that was treated compared to the group that was on the placebo. Our goals with the follow up study was to:

  • Look more carefully and closely at the phenomenon of antibiotic resistance in the organisms in both the treated and untreated population and
  • Learn more in terms of factors associated with the resistance and how that resistance changes over time.

Notes: What were the key goals of the study?

Nelson: The “Antimicrobial Resistance and Urinary Tract Infection Recurrence” study set out to identify the pattern of resistance organisms. We looked at how the resistance pattern among recurrent infection changed – or didn’t change, during the time of the study.

Another goal was to answer the question of whether you can use trimethoprim-sulfamethoxazole for prophylaxis if the index UTI was resistant to this antiobiotic.

Notes: What were the results and how do these findings impact patient care?

Nelson: Probably the most significant finding of the overall resistance pattern was the proportion of infections that were resistant actually decreased during the course of the study. The longer the patients were involved in the study – even the kids who were getting treated that whole time, the less resistance we saw. Which was certainly counter intuitive – most people assume the longer you are treated the more resistance you will have.

In this case, the infections that happened later in the study period – the last 6 months – were much less resistant than the ones we saw early on. There was still resistance as you might expect but not as significant as earlier in the study period.

Another key finding was that trimethoprim-sulfamethoxazole was equally effective in preventing recurrent UTI, whether or not the index UTI was resistant to trimethoprim-sulfamethoxazole. This means that even if the child had a trimethoprim-sulfamethoxazole-resistant UTI, this agent can still be used as prophylaxis.

There were a number of potential reasons:

  • Resistance risk: Overall, it is reassuring to know that the children treated with prolonged preventive antibiotics don’t necessarily have progressive increases in their resistance risk over time. If anything, it goes down.
  • The parallels: We also found when there is resistance the resistance pattern tends to runs parallel with resistance to other antibiotics. The kids whose infections were resistant to trimethoprim-sulfamethoxazole, the antibiotic in question, the same organism was more likely to be resistant to certain other antibiotics – not all but certain others. Even though these kids were not being exposed to these antibiotics.
  • Survival advantage: You assume antibiotic resistance occurs due to evolutionary pressures – the bugs that are better at evading antibiotics obviously have a survival advantage. But there is no survival advantage to becoming resistant to antibiotics that you are NOT being exposed to. There is no selective pressure for that. Yet the resistance we saw did correlate. Not to suggest that some of the mechanisms of resistance and how it is transmitted from one organism to another probably used some common pathways – common transmission mechanisms of bacterial DNA or common biochemical mechanisms that allow them to become resistant to a number of antibiotics.

Notes: What’s next?

Nelson: I think there is obviously a continuing need for more research into what drives antibiotic resistance and how you can mitigate it. The results of this study shows pediatricians or anyone else who treats kids with reflux that:

  • Using prophylaxis antibiotics does result in a decreased risk of infection and
  • Although resistance is more common in the treated group, it tends to decline over time so you can be comfortable that although resistance is more prevalent its not a persistent problem. That should reassuring to those who treat children.

NelsonCaleb-3_ (1)Dr. Caleb P. Nelson, MD, MPH trained in urology at the University of Michigan and in pediatric urology at the Johns Hopkins Hospital. Since 2006, he has been on the staff of Boston Children’s Hospital, with an academic appointment as an Assistant Professor of Surgery (Urology) and Pediatrics at Harvard Medical School. His research interests focus on clinical effectiveness research in pediatric urology, as well as quality of care and patient safety.

 

Learn more about the Department of Urology.

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