Long-term Antibiotics to Prevent Urinary Tract Infection in Children with Isolated Vesicoureteric Reflux: A Placebo-Controlled Randomised Trial.

Jonathan C Craig, MBChB, MMed, PhD, Leslie P Roy BSc, MBBS, Premala Sureshkumar, BSc, John Burke, MBBS, Harley Powell, MBBS, and Elisabeth M Hodson, BSc, MBBS.
Australian and New Zealand Paediatric Nephrology Association, Sydney, NSW, Australia

It is widely recommended that newborns with a family history of vesicoureteric reflux (VUR) or with hydronephrosis on antenatal ultrasonography, be screened for VUR and those affected be given low-dose long-term antibiotics to prevent UTI and renal damage. N placebo-controlled trial has been conducted previously to determine whether this practice is effective. In a multicentre trial, children under 3 months of age with isolated VUR were randomly assigned to 3 years of trimethoprim-sulphamethoxazole at a dose of 2mg/kg/day as a single daily dose (23) or matching placebo (23). Investigators, children and their families, outcome assessors and data analysts were blind to treatment allocation. Analysis was by intention to treat. From 41,000 fetuses screened for renal tract dilatation, 412 newborns with hydronephrosis were eligible, 71 were diagnosed with VUR and 46 were randomised. Most participants were boys (63.0%) and had reflux of grades III-V (65.2%), 18 in the placebo group (78.3%) and 12 in the antibiotic group (52.2%). Five children (3 placebo, 2 antibiotic) were lost to follow-up (10.8%). Two children in the placebo group (10%), and no child in the antibiotic group developed a UTI (exact p=0.2). No child in either group developed new renal damage on DMSA scan. Renal growth (2.42 cm’s vs 2.38 cm’s, p=0.8) and GFR (119 vs 108mLs/min/1.73m2, p=0.3) were no different between the 2 groups. At best, assuming an absolute reduction in risk of UTI of 30% (upper bounds of 95%CI) over 3 years with long-term antibiotic, 2000 fetuses would need to be screened to detect 20 with renal tract dilatation, of which 3 would have VUR. Treating these children for 3 years with daily antibiotics would prevent 1 episode of UTI.

Daily antibiotics given to children with asymptomatic VUR did not reduce significantly the risk of UTI or new renal damage during the first 3 years of life. Given the small sample size of the trial and the low number of events, a beneficial effect of the intervention is possible but unlikely to be of clinical significance.

Presented at American Society of Nephrology 35th Annual Meeting & Scientific Exposition, Philadelphia, Pennsylvania, 30 Oct - 4 Nov 2002.

Correspondence
Jonathan Craig
Centre for Kidney Research
The Children’s Hospital at Westmead
Locked Bag 4001
Westmead NSW 2145 Sydney Australia
Tel: +61 2 9845 3432
Fax: +6 12 9845 3038
Email:Jonathan Craig