Long-term, low-dose trimethoprim-sulfamethoxazole “modestly” decreases the number of urinary tract infections in predisposed children.
However, it remains unknown whether this effect translates into preventing kidney damage from pyelonephritis, and “the magnitude of the benefit is likely to be small at best,” said Dr. Jonathan C. Craig of the University of Sydney and his associates.
The prophylactic use of antibiotics in this patient population is widespread but also has been widely questioned, “since adequately powered and well-designed, placebo-controlled trials … are lacking.” Dr. Craig and his colleagues conducted the Prevention of Recurrent Urinary Tract Infection in Children With Vesicoureteric Reflux and Normal Renal Tracts (PRIVENT) trial to determine whether the treatment is effective (N. Engl. J. Med. 2009;361:1748–59).
They assessed 576 children who had had at least one symptomatic UTI and were treated at four medical centers in Australia. Equal numbers of the study subjects were randomly assigned to receive either daily trimethoprim-sulfamethoxazole or a placebo matched for taste, color, and texture; they were followed at 3-month intervals for 1 year. The median age was 14 months. Most of the subjects were girls (64%), and 42% had known vesicoureteral reflux.
Recurrent UTI, the primary outcome measure, developed in 13% of the antibiotic group and 19% of the placebo group. “At 12 months, 14 patients would need to have been treated to prevent one UTI,” they said. Similarly, urinary tract infection with fever developed in 7% of the antibiotic group and 13% of the placebo group.
However, “any benefits of long-term antibiotic use in reducing the risk of new kidney damage from pyelonephritis remain speculative, since our study was not powered to analyze this outcome,” they noted. The rate of adverse events was not significantly different between the two groups.
Overall, the findings indicate that in children who have had a single UTI, “prophylaxis with trimethoprim-sulfamethoxazole should be considered but not routinely recommended,” Dr. Craig and his associates wrote.
In an editorial comment, Dr. Alejandro Hoberman of Children's Hospital of Pittsburgh and Dr. Ron Keren of Children's Hospital of Philadelphia said that recent smaller clinical trials, which demonstrated no benefit from antibiotic prophylaxis, “led some clinicians to become skeptical about the role of prophylaxis or the need to evaluate children with recurrent UTI for vesicoureteral reflux.” However, these trials were insufficiently powered and were otherwise flawed in their methodology to offer definitive conclusions, they said (N. Engl. J. Med. 2009;361:1804–6).
In contrast, Dr. Craig and his colleagues have established that antibiotic prophylaxis has a “modest but significant” preventive effect. Ongoing trials in Sweden and the United States may determine whether this benefit also prevents actual kidney damage. Until then, “early diagnosis and treatment of UTI and treatment of dysfunctional voiding, which predisposes many children to UTI, are likely to go a long way toward preventing long-term renal damage,” wrote Dr. Hoberman and Dr. Keren.
This study was funded by the National Health and Medical Research Council of Australia and the Financial Markets Foundation for Children of Australia. Dr. Craig, Dr. Hoberman, and Dr. Keren reported no financial conflicts of interest.