Antimicrobial prophylaxis for children at risk for urinary tract infections: implications for adherence assessment
Thomas Gaither, MD, MAS, Hillary Copp, MD, MS.
University of California, San Francisco, San Francisco, CA, USA.
Continuous antimicrobial prophylaxis (prophylaxis) is associated with a reduction in recurrent urinary tract infections in children with vesicoureteral reflux. However, adherence to daily medications has been shown to be poor.
Methods
We conducted a secondary analysis of the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial. We defined non-adherence as taking the study medication less than 75% of the time on average, which was provided via patient questionnaires. We assessed overall non-adherence in the study, predictors of non-adherence, and examined the efficacy of prophylaxis stratified by adherence status. We repeated our efficacy analysis stratified by quartiles of adherence status (1st quartile— 0-70% adherence; 2nd quartile— 71-91% adherence; 3rd quartile— 92-96% adherence; 4th quartile— >96% adherence).
Results
Overall, 170/607 (28%) of the patients met criteria for non-adherence. Neither demographic factors nor disease severity was associated with non-adherence. In the sub-analysis of patients who were toilet trained at baseline, increasing bladder and bowel dysfunction (BBD) symptom score was associated with non-adherence (aOR=1.1 95%CI 1.0-1.2). The protective effect of prophylaxis on recurrent UTI’s in patients who were adherent was strengthened (RR=0.43, 95%CI 0.25-0.72), and the protective effect of prophylaxis on recurrent UTI’s in patients who were non-adherent was diminished (RR=0.74, 95%CI 0.47-1.19). Patients who were non-adherent were at higher risk for renal scars (RR=1.9, 95%CI 0.91-3.97). A dose response relationship was observed among adherence quartiles (Figure 1). Renal scarring in the placebo group ranged from 1.7% predicted probability of scarring in the 1st quartile (most adherent) to 26.3% predicted probability of scarring in the 4th quartile (least adherent). In the prophylaxis group, we observed a u-shape distribution with highest predicted probability of scarring in the 1st quartile (most adherent) at 16.8% and second highest predicted probability of scarring in the 4th quartile (least adherent) at 16.2%. Patients most adherent to prophylaxis were 9.9 times more likely to develop a renal scar compared to patients most adherent to placebo.
Conclusions
Adherence to prophylaxis increases the efficacy of the treatment, whereas non-adherence may place patients at risk for more severe complications, including renal scarring. Patients most adherent to study medications were an exception whereby those most adherent to prophylaxis were roughly 10 times more likely to develop a renal scar compared to patients most adherent to prophylaxis. Adherence should be assessed in prophylaxis management algorithms. The relationships between non-adherence and renal scarring and non-adherence and BBD merit future study. 
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