VUR, UTI, and Antibiotic Prophylaxis How to Use an Article About Therapy or Prevention,Journal Club Amy K Evans PGY2 August 15, 2006,The Case,Kali is a 14mo female who presents to WRAMC ED with fever to 102. Your stellar Peds Intern suggests obtaining a UA/UCx, which results in the diagnosis of acute pyelonephritis.,The Case,Kali is a 14mo female who presents to WRAMC ED with fever to 102. Your stellar Peds Intern suggests obtaining a UA/UCx, which results in the diagnosis of acute pyelonephritis. Kali is admitted to Wd51 for 48hrs of IV abx, then, afebrile, discharged to complete po course.,The Case,Kali is a 14mo female who presents to WRAMC ED with fever to 102. Your stellar Peds Intern suggests obtaining a UA/UCx, which results in the diagnosis of acute pyelonephritis. Kali is admitted to Wd51 for 48hrs of IV abx, then, afebrile, discharged to complete po course. She undergoes renal US and VCUG 3 weeks later, which reveal grade II VUR on the left.,The Question,Should we treat her prophylactically?Short-term: Will this decrease recurrent infections? Long-term: Will this decrease renal scarring? Why else would it matter?,Background,Vesicoureteral Reflux (VUR) Primary congenital incompetence of VU valve (shortened submucosal tunnel) Secondary multiple anatomic abnormalities,Background,Incidence 1-10% Siblings 30-45% (3/4 asymptomatic) Diagnosed via VCUG UTI workup 40% (girls); 70% (infants 1yo) Antenatal hydronephrosis 9% (boys) Why worry? VUR pyelonephritis renal scarring HTN, renal insufficiency, ESRD, pre-eclampsia,Background,Natural hx of VUR: spontaneous resolutionUTI VUR? VUR UTI? VUR Pyelo? VUR Scarring?,Current Treatment Recs,Workup: Febrile UTI (any age) UTI 5yo UTI x2 in school-age girls UTI in any boyTo treat or not to treat?,Imaging: Renal US 40% sensitive (VUR) VCUG Diagnostic! DMSA,AUA Treatment Guidelines,Current Treatment Recs,AUA Pediatric VUR Guidelines Panel (1997) “The panel recommendations to offer continuous abx prophylaxisare based on limited scientific evidence. To our knowledge controlled studies comparing the efficacy of continuous prophylaxis and intermittent therapy on health outcomeshave not been performed.”No controlled studies? Then what are we basing treatment on?,The State of the Art,Williams et.al. (2001) Systematic review of RCTs on UTI/abx prophy Five trials, 1968-1978 Best 2: 71 patients total, normal anatomy, 92% girls Garin et.al. (1998) UTI VUR? no VUR Pyelo? VUR UTI? no Degree VUR Scars? VUR Scarring? no,We Need A Study That,Will help us decide whether or not to prophylax this patientIncludes patients with symptomatic VUR Compares antibiotic prophylaxis to a control Looks at clinically important outcomes,Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study.,Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A, Young L. Pediatrics 2006;117:626-632.,Study Questions,Does VUR correlate with UTI/renal scarring?Does antibiotic prophylaxis correlate with UTI/renal scarring?,Study Design,Randomized, controlled, multicenter trial Inclusion: 3mo-18yo Acute pyelonephritis Exclusion: Grade IV-V VUR Anatomic abnormalities Pregnancy,Study Design,Met inclusion criteria VCUGPyelo treated: IV abx po for 14-day course Abx: TMP/SMX or nitrofurantoin for 1 year,VUR,No VUR,Abx,Abx,No Abx,No Abx,Follow Up,At entry: UA/UCx, DMSA, VCUG, Renal US At Q3mo clinic visit: UA/UCx At 6mo: DMSA At 12mo: VCUG, Renal USEndpoints: Recurrent UTI Renal scarring,Study Results,Analysis of Results,Fishers Exact Test 2x2 comparison tables Control vs. variable Smaller sample size Gives p value Does not give CIGoal: p.05!,http:/www.childrensmercy.org/stats/ask/fishers.asp,Study Results,Recurrence of UTIs Timing Type Recurrent Pyelonephritis & Antibiotics Recurrent Pyelonephritis & VUR Degree Renal Scarring VUR Antibiotics,Study Results,Recurrence of UTI Overall 20.1% VUR not significant No abx (p=.9999) VUR 22.4% No VUR 23.3% Abx (p=0.633) VUR 23.6% No VUR 8.8%,Type of Recurrence Cystitis (no p value) VUR 8.6% No VUR 13.3% Pyelonephritis (p=.3781) VUR 7.1% No VUR 3.8%,Study Results,Recurrent Pyelo and Antibiotics No benefit of abx (p=.0291) 7:1 abx:noneRecurrent Pyelo and VUR Degree 6/8 Grade III (cystitis: 46%) 2/8 Grade II (cystitis: 40%) 4/4 pts without VUR,Study Results,Renal Scarring No evidence VUR increased scarring (p=.9999)VUR (6.2%) = No VUR (5.7%) Abx (7.0%) = No Abx (5.1%)Grade I VUR 5.3% with scars Grade II VUR 5.2% Grade III VUR 13.5%,Study Conclusions,Mild/moderate VUR not associated with UTI, pyelonephritis, or scarringAntibiotic prophylaxis not associated with UTI, pyeloneprhitis, or scarring,Critically Evaluating (JAMA Users Guide),Are the results valid? What were the results? Will the results help me to take care of my patient?,Are the results valid? Primary Guides,