Is continuous antibiotic prophylaxis in children with vesicoureteral reflux really ineffective in preventing pyelonephritis?

Abstract

Sirs, Although long-term antibiotic prophylaxis (AP) has been used for patients with vesicoureteral reflux (VUR) in order to prevent urinary tract infections for many years, recent randomized controlled trials (RCTs) revealed that AP with sulfametoxazole/trimethoprim (SMX/TMP) or nitrofurantoin was ineffective in reducing the rate of recurrence of pyelonephritis in children with low grade VUR and was associated with an increased risk of resistant infections [1– 3]. On the other hand, because of the increase in organisms resistant to SMX/TMP, conventional AP using low-dose cephalosporins, such as cefaclor (CCL), has been favored by many pediatric nephrologists and urologists in Japan for more than 10 years. Although we previously reported the efficacy and safety of the strategies of AP using low doses of CCL for children with VUR in this journal, since then there has been a paucity of evidence for the agent [4]. To investigate whether long-term use of CCL could effectively reduce the risk of recurrent pyelonephritis in comparison with SMX/TMP, we therefore reviewed retrospective data from children with VUR, including grade IV or V, in our hospital. Two hundred and forty-two children (168 male, 74 female) with VUR who had been diagnosed by voiding cystourethrography after acute pyelonephritis and had received AP (CCL or SMX/TMP) for more than 6 months in Saitama Children’s Medical Center from April 1994 to December 2008 were enrolled in this study. The VUR grade was based on the maximum grade on either side of the urinary collecting system (grade I, 7; II, 41; III, 64; IV, 82; V, 48). Of the 242 patients, 184 (76%) had received AP with CCL (5–10 mg/kg per day), while the remaining 58 (24%) had received SMX/TMP (5–10 mg/kg per day SMX and 1–2 mg/kg per day TMP). The choice of antibiotics and the duration of AP depended on the decisions of different physicians. The children’s ages at the first episode of acute pyelonephritis varied from 0.5 months to 127 months (median 4 months). The mean duration of treatment for patients who had received AP was 21±13.5 months. Forty patients (17%) developed breakthrough infections (total 70 episodes) during a total of 5,028 months of treatment (one recurrent pyelonephritis in approximately 72 months). Of these 40 patients, 29 (73%) had high grade VUR (grade IV or V). Table 1 shows the demographic characteristics of the patients who received AP with CCL or SMX/TMP. Although there were no significant differences between the two groups in terms of the gender ratio, the duration of treatment, VUR laterality, or VUR grade, the predicted months for one recurrent episode of pyelonephritis per patient was significantly longer for children on CCL than for those on SMX/TMP (P<0.05). However, children who had received AP with low doses of CCL were more likely to have had breakthrough infections of cephalosporinresistant bacteria other than Escherichia coli, such as Pediatr Nephrol (2009) 24:1431–1432 DOI 10.1007/s00467-009-1161-6