Sunday June 30, 2019 from 11:50 to 12:50
Randomized, blinded, placebo-controlled trial of continuous antibiotic prophylaxis for febrile urinary tract infection prevention in infants with prenatal hydronephrosis: The Alpha study
Luis H. Braga1,5, Melissa McGrath1, Steven Arora2, Martha Fulford3, Armando J. Lorenzo4, Lucy Giglia2, Farough Farrokhyar5.
1Surgery, McMaster University , Hamilton, ON, Canada; 2Pediatrics , McMaster University , Hamilton, ON, Canada; 3Infectious Diseases, Medicine, McMaster University , Hamilton, ON, Canada; 4Urology, The Hospital for Sick Children, Toronto, ON, Canada; 5Epidemiology and Biostatistics, McMaster University , Hamilton, ON, Canada
Introduction: Continuous antibiotic prophylaxis (CAP) to prevent febrile urinary tract infection (fUTI) in infants with prenatal hydronephrosis (PHN) remains controversial, contributing to a lack of consensus guidelines and diverse practice patterns. We aimed to determine whether CAP vs. placebo reduces fUTIs in prenatal HN patients within the first 18 months of life.
Methods: Infants 0–7 months old with PHN were recruited. Inclusion criteria included Society for Fetal Urology (SFU) grade III/IV with/without dilated ureter (>7 mm) or urinary tract dilation (UTD) P2/P3, and voiding cystourethrogram (VCUG) to rule out Vesicoureteral reflux (VUR). Patients received equivalent volumes of trimethoprim (TMP) or placebo (syrup)with a 1:1 allocation ratio, using a computer-generated randomization sequence in random block sizes of four, six, and eight. Trial participants were blinded, except the pharmacist. The primary outcome was catheter specimen fUTIs adjudicated by a three-physician panel. The secondary outcome was bacterial resistance patterns. Intention-to-treat (ITT) analysis to estimate fUTI-free rate was done using Kaplan-Meier curves. A subgroup analysis between ureteropelvic junction obstruction (UPJO)-like vs. non-refluxing primary megaureter (NRPM) was conducted. Followup included monthly phone calls and quarterly ultrasound for 12 months. Compliance was assessed through a medication logbook.
Results: We screened 1435 infants; 1137 did not meet inclusion criteria, 48 refused, and 150 were randomized (75 to placebo/75 to TMP) Four patients withdrew, leaving 146 for analysis. Baseline characteristics were equally distributed between groups (Table 1). Overall fUTI rate was 6% (9/146), with eight events in the placebo group vs. one (TMP-resistant bacteria) in the intervention group (11% vs.1.4%; p=0.03). Eight fUTIs occurred in uncircumcised males and one in a female. NRPM infants had a significantly higher fUTI rate vs. UPJO-like (14% vs.3; p=0.02). Median time to fUTI was three months (Figs. 1A, 1B). Multidrug resistance was higher in placebo vs. intervention patients (42% vs. 22%; p=non-significant). Overall number needed to treat (NNT) was 10 and NNT for NRPM was four.
Conclusions: Patients with SFUIII/IV-PHN receiving placebo were 10 times more likely to develop a fUTI than those on TMP. CAP should be offered to uncircumcised males and those with dilated ureters due to their higher risk of fUTI.