BACKGROUND:
Several thorough trials have assessed the effectiveness of continuous antibiotic prophylaxis (CAP) in preventing urinary tract infections (UTIs) in infants and children with vesicoureteral reflux (VUR), yet its value remains debatable. Uncertainty persists about the risk/benefit ratio of CAP and which specific populations would benefit most. This evaluation covers all recent randomized trials addressing these issues and aim to understand the benefits of CAP for UTI, antibiotic resistance, and renal scarring.
METHODS:
A recent systematic review was referred to for identification of relevant studies. After screening, an additional randomized controlled trial, published after the systematic review, was identified for inclusion. In total, 4 randomized trials comparing CAP to no treatment or placebo were analyzed (Roussey-Kesler 2008; RIVUR 2014; Pennessi 2006; PREDICT 2023). Fragility Index (FI; indicates the number of patients required to convert a positive trial to a negative trial) was calculated for all positive trials. The studies were organized based on their patient characteristics to identify gaps in literature on this topic.
RESULTS:
Among the 4 identified trials, only one study assessed patients <6 months of age and included patients with grade 5 VUR. Two studies, the RIVUR and PREDICT trials, detected statistical significance in their primary outcome of UTI recurrence. The FI for the RIVUR trial and PREDICT trial were 13 and 5, respectively. Although these numbers make the trials appear robust, it is critical to consider that 80 and 49 patients were lost to follow-up in each, thus raising the possibility of a less impressive benefit. On meta-analysis of the primary outcome, CAP appears to have an overall protective effect for UTI occurrence (RR 0.70 [fixed effects, 95% CI 0.58, 0.85], p=0.0003). While the RIVUR trial had a low risk of bias, other studies had moderate to high risk, including the lack of blinding (Figure 1). Among studies reporting antibiotic resistance, 2,4,5 there was a higher likelihood of antibiotic resistance in patients who were on CAP (RR 2.85 [Random Effects, 95% CI 1.94, 4.17], p<0.0001). Moreover, from studies reporting renal scarring,2,4,5 there was no difference in terms of overall or new renal scar development between groups (RR 1.16 [Random Effects, 95% CI 0.88-1.52], p=0.30). There was significant heterogeneity across the studies (I2=74%, p=0.0009), likely attributing to the differences in age group, sex distribution, and VUR grades (Table 1).
CONCLUSIONS:
Current research lacks information on the effectiveness of CAP for both circumcised and uncircumcised males, covering all ages, VUR status, and history of UTIs. Current data is particularly scarce for those at highest risk, such as uncircumcised infants with prior UTIs and high-grade VUR, who might benefit most from CAP. Limited studies suggest that infants with low-grade VUR may be safely monitored without CAP (Table 1).
