Antibiotic prophylaxis in the management of vesicoureteric reflux: a randomized double-blind placebo-controlled trial
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The benefits of long-term low-dose antibiotics in preventing urinary tract infection (UTI) and renal damage in children with primary vesicoureteric reflux (VUR) are unclear.
Children aged between 1 and 12 years with VUR grade I–IV and a microbiologically proven UTI were randomized into two groups to receive either antibiotic prophylaxis [2 mg/kg trimethoprim + sulfamethoxazole (TMP-SMX)] daily or placebo, respectively, for 12 months. Primary outcome was microbiologically confirmed symptomatic UTI. Intention-to-treat analysis using time-to-event data was performed.
A total of 93 children (66.7 % boys) with a median age of 4.6 years were enrolled in this study; VUR grade III–IV was present in 73.1 % of these children. At least one symptomatic UTI occurred in ten (21.3 %) patients receiving antibiotic prophylaxis and in three (6.5 %) patients receiving placebo [hazard ratio in antibiotic group 3.9; 95 % confidence interval (CI) 1– 14; log rank test P = 0.02). Compared to the group receiving placebo, the antibiotic group had a 14.8 % increased risk for developing UTI (95 % CI 1–28; P = 0.03). Of the total number of episodes of UTI, 58.3 % of those in the antibiotic group were caused by TMP-SMX-resistant bacteria compared to 20 % in the placebo group (P = 0.15). A renal scan at 12 months revealed that six of 37 (16.2 %) patients in the antibiotic group and seven of 43 (16.3 %) patients in the placebo group had new or worsening of pre-existing scar.
Long-term antibiotic prophylaxis with TMP-SMX is associated with increased risk of symptomatic UTI compared to placebo in children with grade I–IV VUR.
KeywordsUrinary tract infection Trimethoprim–sulphamethoxazole Asymptomatic bacteriuria Bacterial resistance DMSA scan Renal scar
The study was funded by the Indian Council of Medical Research.
- 8.Elder JS, Peters CA, Arant BS Jr, Ewalt DH, Hawtrey CE, Hurwitz RS, Parrott TS, Snyder HM 3rd, Weiss RA, Woolf SH, Hasselblad V (1997) Pediatric vesicoureteral reflux guidelines panel summary report on the management of primary vesicoureteral reflux in children. J Urol 157:1846–1851PubMedCrossRefGoogle Scholar
- 10.Montini G, Rigon L, Zucchetta P, Fregonese F, Toffolo A, Gobber D, Cecchin D, Pavanello L, Molinari PP, Maschio F, Zanchetta S, Cassar W, Casadio L, Crivellaro C, Fortunati P, Corsini A, Calderan A, Comacchio S, Tommasi L, Hewitt IK, Da Dalt L, Zacchello G, Dall'Amico R, IRIS Group (2008) Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Pediatrics 122:1064–1071PubMedCrossRefGoogle Scholar
- 11.Pennesi M, Travan L, Peratoner L, Bordugo A, Cattaneo A, Ronfani L, Minisini S, Ventura A, North East Italy Prophylaxis in VUR study group (2008) Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Pediatrics 121:e1489–e1494PubMedCrossRefGoogle Scholar
- 12.Roussey-Kesler G, Gadjos V, Idres N, Horen B, Ichay L, Leclair MD, Raymond F, Grellier A, Hazart I, de Parscau L, Salomon R, Champion G, Leroy V, Guigonis V, Siret D, Palcoux JB, Taque S, Lemoigne A, Nguyen JM, Guyot C (2008) Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. J Urol 179:674–679PubMedCrossRefGoogle Scholar
- 17.Craig JC, Simpson JM, Williams GJ, Lowe A, Reynolds GJ, McTaggart SJ, Hodson EM, Carapetis JR, Cranswick NE, Smith G, Irwig LM, Caldwell PH, Hamilton S, Roy LP (2009) Prevention of recurrent urinary tract infection in children with vesicoureteric reflux and normal renal tracts (PRIVENT) investigators antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med 361:1748–1759PubMedCrossRefGoogle Scholar
- 19.Nagler EV, Williams G, Hodson EM, Craig JC (2011) Interventions for primary vesicoureteric reflux. Cochrane Database Syst Rev 15:CD001532Google Scholar
- 21.Nakai H, Kakizaki H, Konda R, Hayashi Y, Hosokawa S, Kawaguchi S, Matsuoka H, Nonomura K, Shimada K, Kawamura T (2003) Prospective study committee of reflux nephropathy forum, Japan. Clinical characteristics of primary vesicoureteral reflux in infants: multicenter retrospective study in Japan. J Urol 169:309–312PubMedCrossRefGoogle Scholar