Antibiotic Prophylaxis for Recurrent Urinary Tract Infections in Children
Antibiotic Prophylaxis for Recurrent Urinary Tract Infections in Children
Abstract & Commentary
By Hal B. Jenson, MD, FAAP, Professor of Pediatrics, Tufts University School of Medicine, and Chief Academic Officer, Baystate Medical Center, Springfield, MA, is Associate Editor for Infectious Disease Alert.
Dr. Jenson reports no financial relationships relevant to this field of study.
Synopsis: The benefits of long-term, low-dose antibiotic prophylaxis to prevent recurrent urinary tract infection among predisposed children are modest (six percentage points); 14 children would require treatment for 12 months to prevent one urinary tract infection.
Source: Craig JC, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med. 2009; 363:1748-1759.
A prospective, multi-center, double-blind, placebo-controlled, randomized trial of daily trimethoprim-sulfamethoxazole (TMP-SMZ; 2 mg TMP and 10 mg SMZ per kg) vs. placebo was conducted in four centers in Australia during 1998-2007 among children birth to 18 years of age with a history of at least one symptomatic, culture-proven urinary tract infection. All children received TMP-SMZ for two weeks during a single-blind run-in period, followed by randomization to TMP-SMZ or placebo (matched for color, taste, and texture) for 12 months. Clinical and demographical characteristics were comparable between the two groups. The median age at enrollment was 14 months, 64% were girls, and 71% were enrolled after the first documented urinary tract infection. Urinary tract imaging was not mandated; vesicoureteral reflux was documented in 42% of patients, with 53% of these having Grade III reflux.
Recurrent urinary tract infection developed in 36 of 288 patients (13%) in the TMP-SMZ group compared to 55 of 288 (19%) in the placebo group (hazard ratio in the TMP-SMZ group of 061; 95% CI, 0.40 to 0.93; p =0.02). The reduction in the absolute risk of urinary tract infection (six percentage points) appeared consistent across all subgroups of patients — age, sex, reflux status, history of more than one urinary tract infection, or susceptibility of the index organism to TMP-SMZ. Thus, at 12 months, 14 patients (95% CI, 9 to 86) would have to be treated to prevent one urinary tract infection.
One-half of the repeat infections in the placebo group occurred in the first three months, and one-quarter occurred in the second three months. Escherichia coli was the most common organism in the TMP-SMZ group (30 of 36 patients) and in the placebo group (46 of 55 patients).
Very few patients had worsening of renal scanning results, with no significant differences between the two groups. Fewer hospitalizations and adverse drug events occurred in the TMP-SMZ group compared to the placebo group, but the differences were not significant. A test for trend, although not significant, showed that children in the placebo group were more likely to receive multiple courses of antibiotics than were children in the TMP-SMZ group.
Commentary
Urinary tract infection is common among children and affects 8% of girls and 2% of boys by seven years of age. Daily, secondary prophylaxis with low-dose oral antibiotics has been advocated traditionally to reduce the risk of renal damage associated with recurrent urinary tract infections, especially in the presence of vesicoureteral reflux. There has been a dearth of controlled trials to justify this widespread practice. Recent studies published in 2006 (one study) and 2008 (three studies) found no benefit from antibiotic prophylaxis on reducing the incidence of urinary tract infection. Those studies had 218, 225, 100, and 338 subjects, compared to 576 in this new study, which appears to have contributed to limited statistical power of the previous studies to detect such a modest effect.
This study showed that the benefit of prophylaxis was greatest during the first six months. These results of modest reduction in the absolute risk of urinary tract infection in predisposed children (six percentage points), coupled with the low risk of new renal damage occurring with a single urinary tract infection (approximately 5%), suggest that the benefits of long-term, low-dose prophylaxis are small when applied across all patient groups. Additional randomized, controlled studies are underway to define which patient subgroups might have greater benefit from secondary prophylaxis.
A prospective, multi-center, double-blind, placebo-controlled, randomized trial of daily trimethoprim-sulfamethoxazole (TMP-SMZ; 2 mg TMP and 10 mg SMZ per kg) vs. placebo was conducted in four centers in Australia during 1998-2007 among children birth to 18 years of age with a history of at least one symptomatic, culture-proven urinary tract infection.Subscribe Now for Access
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