Antibiotic prophylaxis in the management of vesicoureteric reflux: a randomized double-blind placebo-controlled trial
Pankaj Hari1, Smriti Hari, Aditi Sinha
1Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India, pankajhari@hotmail.com.
Insights
Long-term antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) did not prevent urinary tract infections (UTIs) in children with vesicoureteric reflux (VUR). The TMP-SMX group had a higher risk of symptomatic UTIs compared to placebo.
Area of Science:
- Pediatric Nephrology
- Infectious Diseases
- Clinical Pharmacology
Background:
- The efficacy of long-term, low-dose antibiotics in preventing urinary tract infections (UTIs) and renal damage in children with primary vesicoureteric reflux (VUR) remains uncertain.
- Primary VUR is a significant risk factor for recurrent UTIs and potential renal scarring in pediatric populations.
Purpose of the Study:
- To evaluate the effectiveness of long-term antibiotic prophylaxis in preventing symptomatic UTIs in children diagnosed with VUR.
- To assess the impact of antibiotic prophylaxis on the development or worsening of renal scarring.
Main Methods:
- A randomized controlled trial involving children aged 1-12 years with VUR (grades I-IV) and a history of microbiologically confirmed UTI.
- Participants were randomized to receive daily trimethoprim-sulfamethoxazole (TMP-SMX) or a placebo for 12 months.
- The primary outcome was the incidence of microbiologically confirmed symptomatic UTI, analyzed using time-to-event data.
Main Results:
- A total of 93 children were enrolled; 73.1% had VUR grades III-IV. The TMP-SMX group experienced a higher incidence of symptomatic UTIs (21.3%) compared to the placebo group (6.5%), with a hazard ratio of 3.9 (P=0.02).
- The antibiotic group showed a 14.8% increased risk for developing UTIs (P=0.03). Notably, 58.3% of UTIs in the antibiotic group were caused by TMP-SMX-resistant bacteria, versus 20% in the placebo group (P=0.15).
- Renal scans at 12 months indicated no significant difference in new or worsening scars between the groups (16.2% in the antibiotic group vs. 16.3% in the placebo group).
Conclusions:
- Long-term antibiotic prophylaxis with TMP-SMX is associated with an increased risk of symptomatic UTIs in children with VUR grades I-IV.
- The findings suggest that TMP-SMX prophylaxis may not be beneficial and could potentially increase the risk of UTIs, possibly due to the emergence of resistant bacteria.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
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