Continuous antibiotic prophylaxis lowers UTI risk, but ups multidrug resistance

Last Updated: 2018-06-29

By Will Boggs MD

NEW YORK (Reuters Health) - Continuous antibiotic prophylaxis in children with vesicoureteral reflux (VUR) cuts the risk of urinary tract infection (UTI), but increases uropathogen multidrug resistance, according to a new meta-analysis.

"The decision to treat with continuous antibiotic prophylaxis is complex and requires an understanding not only of the benefits of reducing recurrent urinary tract infections but also the potential harm of propagating drug resistance," Dr. Hilary J. Copp from the University of California, San Francisco, told Reuters Health by email.

Children with VUR are often managed with continuous antibiotic prophylaxis aimed at preventing recurrent UTIs and their complications. Several studies have found that prolonged administration of antibiotics can increase the risk of uropathogen resistance for the antibiotics used for prophylaxis.

Dr. Copp and colleagues evaluated the impact of continuous antibiotic prophylaxis on the development of recurrent UTI with acquired multidrug resistance in their meta-analysis of individual data from 1,299 children with VUR who participated in randomized controlled trials, including 224 with first recurrent UTIs.

Multidrug resistance rates in the six studies in the analysis ranged from 0% to 62%, the team reports in Pediatrics, online June 28.

Children being treated with prophylaxis were significantly more likely to have a multidrug-resistant first recurrent UTI (33% vs. 6% of those not receiving prophylaxis) and were subsequently more likely to receive a broad-spectrum antibiotic for treatment of the recurrent UTI (68% vs. 49%, respectively).

After adjustment for potential confounding factors, children receiving prophylaxis had 6.4 times higher odds of a multidrug-resistant first infection, compared with untreated controls, which represents one additional multidrug-resistant recurrent UTI for every 21 patients with VUR treated with prophylaxis.

Moreover, children who had a history of multidrug-resistant UTI at enrollment had 4.1 times the odds of developing a multidrug-resistant first recurrent UTI compared with those whose previous UTI at enrollment was not multidrug-resistant.

Children treated with continuous antibiotic prophylaxis had significantly lower rates of recurrent UTI (18.3%) than did controls (23.1%), which represents one fewer recurrent UTI for every 21 patients with VUR treated.

"These findings create significant tension in the risk-benefit assessment of continuous antibiotic prophylaxis," Dr. Copp said. "This is a complex decision that requires open communication with the patient's family balancing the desire to avoid a urinary tract infection by treating with a daily medication versus the potential for breakthrough multidrug resistant infection requiring more complex treatment with broad-spectrum antibiotics. Guiding this decision is the individual patient risk profile for developing a urinary tract infection, which may be increased in those with higher-grade vesicoureteral reflux, prior UTI, bladder and bowel dysfunction, and renal scarring."

Dr. Yair Lotan from UT Southwestern Medical Center at Dallas, Texas, who recently evaluated the cost-effectiveness of antimicrobial prophylaxis for children with VUR, told Reuters Health by email, "VUR is a common problem, and UTIs in children can have an impact not only on the child but also on the parents."

"Even though prophylaxis increased the risk for resistant organisms, it was still relatively low overall and should not dissuade parents and physicians from considering prophylaxis," he said. "However, appropriate counseling is important to weigh the pros/cons of observation versus prophylaxis versus treating the reflux."

"One consideration for parents is what to do if your child has already had more than 1 infection and yet you want to avoid surgery to correct the reflux," said Dr. Lotan, who was not involved in the new research. "Even in this meta-analysis, at baseline patients in the prophylaxis group were much more likely to have had a UTI before the study (26% vs. 8%). It seems that parents may be willing to start with a strategy of prophylaxis to reduce infection but if there is a recurrence then it suggests that strategy may not be effective. Furthermore, if there is a pattern of resistance, then it may add more incentive to correct the problem surgically."

SOURCE: https://bit.ly/2tEVE6X

Pediatrics 2018.