Antibiotic prophylaxis can prevent recurrent infection in children with urinary tract infections
Article Outline
- Question
- Design
- Setting
- Participants
- Intervention
- Outcomes
- Main Results
- Conclusions
- Commentary
- References
- Copyright
Craig J, Simpson J, Williams G, Lowe A, Reynolds G, McTaggart S, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med 2009;361:1748-59.
Question
Among children with a history of urinary tract infection (UTI), will low-dose antibiotics (compared with placebo) prevent recurrent UTIs?
Design
Randomized controlled trial.
Setting
Four medical centers in Australia.
Participants
A total of 576 children (median age at entry of 14 months). Sixty-four percent of the patients were girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these patients), and 71% were enrolled after the first diagnosis of urinary tract infection.
Intervention
Enrolled children received either daily trimethoprim-sulfamethoxazole suspension (as trimethoprim 2 mg ' sulfamethoxazole 10 mg/kg body weight) or placebo for 12 months.
Outcomes
Microbiologically confirmed symptomatic urinary tract infection.
Main Results
UTI developed in 36 of 288 patients (13%) in the group receiving trimethoprim-sulfamethoxazole (antibiotic group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P = .02 by the log-rank test, number needed to treat = 17). In the antibiotic group, the reduction in the absolute risk of urinary tract infection (6 percentage points) appeared to be consistent across all subgroups of patients (P ≥ .20 for all interactions).
Conclusions
Long-term, low-dose trimethoprim–sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children. The treatment effect appeared to be consistent, but modest, across subgroups.
Commentary
Antibiotic prophylaxis has been a routine recommendation in the management of children determined to have vesicoureteral reflux in the context of radiographic evaluation of their first episode of urinary tract infection (UTI). The intent of the prophylaxis is the prevention of subsequent episodes of UTI which might lead, in the short term, to increased morbidity and, in the long term, to renal scarring and complications such as hypertension, preeclampsia, and end-stage renal disease. In recent years, there have been several publications that have challenged the idea that prophylaxis is beneficial.1 Most of these studies have had relatively small sample sizes and other methodologic flaws that have weakened the credibility of their conclusions. Although antimicrobial prophylaxis is biologically plausible as a strategy to prevent UTI, 2 factors mitigate against success: (1) the likelihood of adherence to daily medications for prolonged periods and (2) the emergence of antibiotic resistance, which renders the prophylactic agent ineffective. This study sought to establish the potential usefulness of prophylaxis in the prevention of subsequent episodes of UTI in a large cohort of children between birth and 18 years of age who had previously experienced at least 1 episode of UTI. The children either had to have vesicoureteral reflux (of any degree) or a history of recurrent infections. The study was not powered to answer the more fundamental question of the prevention of renal scarring. Although it is desirable to prevent the morbidity of infection, some of which may result in hospitalization, the more important outcome is the prevention of scarring. This study provides unequivocal evidence that sulfamethoxazole-trimethoprim is superior to placebo in the prevention of UTI and, at least in this cohort, is unassociated with serious side effects. However, the study demonstrates the inherent difficulty of adherence to long term medications, as almost half of the study cohort had stopped taking the medication by 12 months. Furthermore, the benefit of prophylaxis appears to be extremely modest, a difference of only 6% between the rate of UTI in children receiving antimicrobial (13%) and those receiving placebo (19%). Accordingly, the authors recommend that the strategy of prophylaxis be reserved for children with previous episodes of severe infection. Ongoing randomized, controlled trials in Sweden and the United States will provide additional information to help practitioners decide the most prudent management for young children with UTI who are determined to have vesicoureteral reflux.2
References
PII: S0022-3476(10)00197-6
doi:10.1016/j.jpeds.2010.02.053
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