Antimicrobial prophylaxis does not reduce recurrent UTI risk in children (but does increase resistance)

Prophylactic antibiotics for children thought to be at risk of recurrent urinary tract infection (UTI) do not appear to influence risk of recurrence, but do increase the risk of infection with resistant bacteria according to the results of a cohort study published in JAMA today. The authors note that there it little primary care-based data on the incidence of recurrent UTI, and that most available data is derived from secondary care populations. US guidelines on the management of children with a first UTI recommend imaging for vesicoureteral reflux (VUR) and prophylactic antibiotic treatment if this is present: these recommendations are based on theory, however, and there is little evidence for them. Some recent research suggests that antibiotic prophylaxis is ineffective in this situation, and there is concern over the development of resistance. This study aimed, therefore, to gather data on the risk factors for recurrent UTI in children in primary care, to determine whether antimicrobial prophylaxis altered the risk of recurrence, and to examine risk factors for development of bacterial resistance.

The authors assembled a cohort of children aged six and under at entry who had been diagnosed with a first episode of UTI in 27 paediatric practices in three US states between mid-2001 and mid-2006. The practices share a common health record, and were located in urban, suburban, and semi-rural areas; the record includes demographic, administrative, and laboratory data as well as clinical data. The initial cohort comprised all children aged under six with two or more clinic visits; those with a diagnosis of UTI were analysed further. Exclusion criteria included previous UTI, and underlying conditions that could increase UTI risk. Primary outcome was time to recurrent UTI.

A total of 74,974 children had two or more clinic visits over the study period, and of these, 666 had a first UTI with no co-morbid conditions to give a first-UTI incidence in otherwise healthy children of 0.007 per person-year. Of these, 55 had less than two weeks observation and could not be analysed, leaving 611 for final analysis. Most of the 611 were female (88.9%) and aged two to six years. Two-thirds had not been screened for VUR and most (79.1%) did not receive antimicrobial prophylaxis. There were 83 (3.6%) who had a recurrent UTI to give a recurrence rate of 0.12 per person-year, and 51 recurrences were caused by an organism resistant to any antimicrobial. Factors that increased risk of recurrence included age, and severe (grade 4 to 5) VUR, but not less severe VUR (grade 1 to 3). Antimicrobial prophylaxis had no effect on risk of recurrence, however it was associated with increased risk of recurrence with resistant bacteria (odds ratio 7.5, 95% CI 1.60 to 35.17).

The authors conclude that in their study population, antimicrobial prophylaxis in children with UTI was not associated with a reduction in risk of recurrence, however it was associated with an increase in the risk of infection with resistant bacteria. They note that their study is the first to produce an estimate of the incidence of recurrent UTI in children in a primary care setting: their value for first UTI is consistent with previously published population-based estimates, however the value for recurrence is much lower than that previously published and derived from referral populations. The results also provide other valuable data on factors affecting risk of UTI recurrence in children. Further studies are needed to expand their results, and to study the risks and benefits of antimicrobial prophylaxis in this patient group.

JAMA 2007; 298; 179-86 (link to abstract)