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INTRODUCTION: Evidence suggests that children with vesicoureteral reflux(VUR) should be maintained on continuous antibiotic prophylaxis(CAP) until toilet training to prevent urinary tract infections(UTI). We have had the opportunity to challenge this concept at our institution by prospectively following 2 cohorts, managed by 2 surgeons with differing practices regarding the age of CAP discontinuation(CAP-DC). Our objective was to compare UTI rates between the 2 cohorts and the antimicrobial resistance pattern. We hypothesized that UTI rates would be similar for both cohorts, with the early CAP-DC group having a more favorable antibiotic resistance profile.
METHODS: We prospectively followed 2 cohorts of patients with primary VUR from 2008-16(n=171): Cohort-I had CAP-DC between ages of 12-18mos and Cohort-II at toilet training age(24-36mos). Age at and mode of presentation, gender, VUR and hydronephrosis(HN) grades, presence of hydroureter, UTI and surgery rates, and follow-up time were collected. Our primary outcome was development of UTI post-CAP-DC in both groups. The secondary outcome was antibiotic resistance rates in those who developed UTIs. We performed subgroup analyses to determine risk factors for UTI post-CAP-DC in both cohorts. Statistical analyses consisted of chi-square for categorical data, t-tests for continuous variables and Kaplan-Meier curves.
RESULTS: Of 171 VUR patients, 113-66%(Cohort-I) stopped CAP at a median age of 16mos and 58-44%(Cohort-II) at 26mos. Patient characteristics are displayed in Table-1. The median age at presentation were 4(IQR: 6) and 6(IQR: 13)mos for Cohort-I and Cohort-II, respectively(p=0.06). Follow-up was 28+20mos for Cohort-I vs.43+36mos for Cohort-II(p<0.01). Gender distribution and mode of presentation were similar between cohorts, as was the type of VUR. There were more patients with dilating VUR(3-5) (102/113;90%) in Cohort-I vs.Cohort-II(46/58;79%)(p=0.06). A total of 20 patients developed UTI post-CAP-DC [14/62(23%) vs. 6/30(20%);p=0.81] and the mean time to UTI post-CAP-DC was 11+12mos for Cohort-I vs. 18+26mos for Cohort-II(p=0.12). Both groups had similar rates of surgery for VUR correction (16%vs.17% for Cohort-I and II, respectively). Of the 20 patients who developed UTI post-CAP-DC, urine culture reports were available for 15(75%): 10(66%) had UTI caused by E-Coli, 7(48%) were resistant to Trimethoprim, Ampicillin or Cefazolin, with the remaining 8(52%) showing no resistance. There were no differences between the cohorts in regards to the resistance pattern.
CONCLUSION: Stopping CAP in VUR children at a median age of 16mos did not result in more UTIs when compared to the traditional approach. By adopting such strategy, duration of antibiotic exposure may be decreased without adversely increasing UTI rates. Discontinuation of CAP early may be more beneficial for males as 75% of patients who had UTIs post-CAP-DC were females.
Table 1: Patient Characteristics

	Cohort I n=113 (%)	Cohort II n=58 (%)	p value
Median age at baseline (months) (IQR)	4(5.6)	6(13.0)	0.06
Gender Uncircumcised Male Circumcised Male Female	34 (30) 21 (19) 58 (51)	24 (42) 6 (10) 28 (48)	0.21
Mode of Presentation Prenatal Postnatal	38 (34) 75 (66)	14 (24) 44 (76)	0.22
BBD/ Constipation Yes No	6 (5) 107 (95)	9 (16) 49 (84)	0.04
Mean CAP-DC (months)	n=62 21+17 median: 16	n=30 33+25 median: 26	<0.01
VUR Grade Non-Dilating (1-2) Dilating (3-5)	11 (10) 102 (90)	12 (21) 46 (79)	0.06
Type of VUR Active Passive	57 (50) 56 (50)	30 (52) 28 (48)	0.87
UTI post-CAP-DC	14 (23)	6 (20)	0.81
Time to UTI post-CAP-DC (months)	12+12 Median: 9	18+26 Median: 8	0.12
Surgery	18 (16)	10 (17)	0.82
Follow up time (months)	28+20 Median: 26	43+36 median: 39	<0.01

Table 2: Univariate analysis of risk factors for developing a UTI post-CAP-DC

	UTI n=20 (%)	Total N=92	p-value
Cohort I Cohort II	14 (22) 6 (20)	62 30	0.78
Gender Female Male Uncircumcised Circumcised	15 (32) 5 (11) 4 (15) 1 (5)	47 45 26 19	0.02 0.38
VUR Non Dilating (I-II) Dilating (III-V)	2 (22) 18 (22)	9 83	1.00
BBD/Constipation Yes No	1 (25) 19 (21)	4 89	1.00
VUR Correcting Surgery Yes No	12 (63) 8 (11)	19 73	<0.01