Antibiotic Prophylaxis for Children with Primary Vesicoureteral Reflux: Where Do We Stand Today?

The main goal of the management of vesicoureteral reflux (VUR) is prevention of recurrent urinary tract infections (UTIs), and thereby prevention of renal parenchymal damage possibly ensuing from these infections. Long-term antibiotic prophylaxis is common practice in the management of children with VUR, as recommended in 1997 in the guidelines of the American Urological Association. We performed a systematic review to ascertain whether antibiotics can be safely discontinued in children with VUR and whether prophylaxis is effective in the prevention of recurrent UTIs and renal damage in these patients. Several uncontrolled studies indicate that antibiotic prophylaxis can be discontinued in a subset of patients, that is, school-aged children with low-grade VUR, normal voiding patterns, kidneys without hydronephrosis or scars, and normal anatomy of the urogenital system. Furthermore, a few recent randomized controlled trials suggest that antibiotic prophylaxis offers no advantage over intermittent antibiotic therapy of UTIs in terms of prevention of recurrent UTIs or new renal damage.

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Continuous antibiotic prophylaxis in the setting of prenatal hydronephrosis and vesicoureteral reflux

Canadian Urological Association Journal ◽

10.5489/cuaj.4387 ◽

2017 ◽

Vol 11 (1-2S) ◽

pp. 20 ◽

Cited By ~ 5

Author(s):

Nathan C. Wong ◽

Martin A. Koyle ◽

Luis H. Braga

Keyword(s):

Antibiotic Prophylaxis ◽

Vesicoureteral Reflux ◽

Randomized Trials ◽

Meta Analysis ◽

The Other ◽

Number Needed To Treat ◽

Low Grade ◽

Prenatal Hydronephrosis ◽

Meta Analyses ◽

Tract Infections

Continuous antibiotic prophylaxis (CAP) has traditionally been offered for children with recurrent urinary tract infections (UTIs) or those at risk, including children diagnosed with prenatal hydronephrosis (HN) and vesicoureteral reflux (VUR). However, indications for antibiotic prophylaxis are controversial, data on who should benefit from this therapy is conflicting and, thus, guidelines are unable to provide conclusive recommendations. In the setting of prenatal HN, although randomized trials are currently underway, most evidence is derived from low- to moderate-quality observational studies. Although there is no benefit in those with low-grade HN, a systematic review of the available studies showed that highgrade HN patients on prophylaxis experienced fewer infections with an estimated number needed to treat of 7. On the other hand, there are eight randomized trials that have investigated the use of antibiotic prophylaxis in the setting of VUR. Although four of the studies have demonstrated some value of prophylaxis and the other four have not, meta-analysis has shown an overall benefit of antibiotic prophylaxis in preventing infections. The observed differences are likely due to different inclusion criteria and study heterogeneity. Although generalizing results of meta-analyses to all children is tempting, an individualized approach, by determining which patients best behave like those of the included studies, is recommended.

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Characterizing Patients with Recurrent Urinary Tract Infections in Vesicoureteral Reflux: A Pilot Study of the Urinary Proteome

Molecular & Cellular Proteomics ◽

10.1074/mcp.ra119.001873 ◽

2020 ◽

Vol 19 (3) ◽

pp. 456-466 ◽

Cited By ~ 2

Author(s):

Dijana Vitko ◽

Patricia S. Cho ◽

Stephen A. Kostel ◽

Shannon E. DiMartino ◽

Lily D. Cabour ◽

...

Keyword(s):

Urinary Tract ◽

Vesicoureteral Reflux ◽

Urinary Tract Infections ◽

Study Cohort ◽

Low Grade ◽

Urinary Proteins ◽

Recurrent Utis ◽

Urinary Proteome ◽

Recurrent Urinary Tract Infections ◽

Tract Infections

Recurrent urinary tract infections (UTIs) pose a significant burden on the health care system. Underlying mechanisms predisposing children to UTIs and associated changes in the urinary proteome are not well understood. We aimed to investigate the urinary proteome of a subset of children who have vesicoureteral reflux (VUR) and recurrent UTIs because of their risk of developing infection-related renal damage. Improving diagnostic modalities to identify UTI risk factors would significantly alter the clinical management of children with VUR. We profiled the urinary proteomes of 22 VUR patients with low grade VUR (1–3 out of 5), a history of recurrent UTIs, and renal scarring, comparing them to those obtained from 22 age-matched controls. Urinary proteins were analyzed by mass spectrometry followed by protein quantitation based on spectral counting. Of the 2,551 proteins identified across both cohorts, 964 were robustly quantified, as defined by meeting criteria with spectral count (SC) ≥2 in at least 7 patients in either VUR or control cohort. Eighty proteins had differential expression between the two cohorts, with 44 proteins significantly up-regulated and 36 downregulated (q <0.075, FC ≥1.2). Urinary proteins involved in inflammation, acute phase response (APR), modulation of extracellular matrix (ECM), and carbohydrate metabolism were altered among the study cohort.

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Faculty Opinions recommendation of Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1103891.793500790 ◽

2014 ◽

Author(s):

Craig Peters

Keyword(s):

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Antibiotic Prophylaxis ◽

Vesicoureteral Reflux ◽

Recurrent Urinary Tract Infection ◽

Randomized Study ◽

Prospective Randomized Study ◽

Low Grade

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Antibiotic Prophylaxis for the Prevention of Recurrent Urinary Tract Infection in Children With Low Grade Vesicoureteral Reflux: Results From a Prospective Randomized Study

The Journal of Urology ◽

10.1016/j.juro.2007.09.090 ◽

2008 ◽

Vol 179 (2) ◽

pp. 674-679 ◽

Cited By ~ 219

Author(s):

G. Roussey-Kesler ◽

V. Gadjos ◽

N. Idres ◽

B. Horen ◽

L. Ichay ◽

...

Keyword(s):

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Antibiotic Prophylaxis ◽

Vesicoureteral Reflux ◽

Recurrent Urinary Tract Infection ◽

Randomized Study ◽

Prospective Randomized Study ◽

Low Grade

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Long-term follow-up of children with vesicoureteral reflux with and without antibiotic prophylaxis

Scandinavian Journal of Infectious Diseases ◽

10.1080/00365540500279918 ◽

2005 ◽

Vol 37 (11-12) ◽

pp. 842-845 ◽

Cited By ~ 24

Author(s):

H Georgaki-Angelaki ◽

S Kostaridou ◽

G. L Daikos ◽

A Kapoyiannis ◽

Z Veletzas ◽

...

Keyword(s):

Antibiotic Prophylaxis ◽

Vesicoureteral Reflux ◽

Long Term Follow Up

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Oral D mannose in the prevention and treatment of recurrent urinary tract infections: A review

Urogynaecologia ◽

10.4081/uij.2021.239 ◽

2021 ◽

Vol 33 (1) ◽

Author(s):

Daniele Porru ◽

Annalisa De Silvestri ◽

Edda Buffa ◽

Catherine Klersy ◽

Barbara Gardella ◽

...

Keyword(s):

Urinary Tract ◽

Antibiotic Prophylaxis ◽

Urinary Tract Infections ◽

Resistant Bacteria ◽

Control Groups ◽

Recurrent Utis ◽

Recurrent Urinary Tract Infections ◽

Long Term Treatment ◽

Significant Difference ◽

Tract Infections

The results of several studies reveal that antibiotics may promote treatment resistance by causing alterations in the intestinal flora. The development of a gut reservoir of resistant bacteria promotes the development of UTIs through autoinfection. This review aims to address clinical reliability, efficacy and safety of long-term treatment with oral D mannose for the prevention of Recurrent Urinary Tract Infections (RUTI) in females. A comprehensive MEDLINE, Embase, Scopus and Cochrane search was performed for English language reports published before December 2018 using the term “recurrent urinary tract infections and D mannose” was carried out. We searched Medline, Embase, Scopus and the Cochrane Register of Controlled Trials from January 2010 to December 2018. Eligible studies did not include non-oral therapy, local (vaginal) treatment in women with recurrent UTIs. We identified eligible original articles. A few limitations of the review are the heterogeneity of the available studies, their different rational and aim, the assumption of D mannose for prophylaxis or treatment of recurrent UTIs. Oral D mannose performs well in the prevention of UTIs recurrences, significant improvement of urinary symptoms was observed, the disease- free time was longer in the groups of patients under prophylaxis with D mannose in comparison with control groups (no treatment, antibiotic prophylaxis, prophylaxis with Proanthocyanidin (PAC) etc. The review has limitations, as the studies are heterogeneous, the meta-analysis requires classifications that can also be arbitrary. Furthermore, single-arm studies are not included. Some of the authors found this evidence inconclusive, which results as a limitation of the study. D mannose prolonged the recurrence-free interval of recurrent UTIs, thus reducing the prolonged or cyclical use of antibiotics, improving clinical symptoms, with a significant difference between treatment and control groups (no treatment, antibiotic prophylaxis, prophylaxis with Proanthocyanidin). However, most clinical trials used an association of different substances commingled with D mannose, dosages and regimens of D mannose were different. For this reason, the evidence of the efficacy of D mannose remains low.

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Antibiotic prophylaxis for prevention of urinary tract infections in the first year of life in children with vesicoureteral reflux diagnosed in the workup of antenatal hydronephrosis: a systematic review

Pediatric Nephrology ◽

10.1007/s00467-020-04568-6 ◽

2020 ◽

Vol 35 (9) ◽

pp. 1639-1646

Author(s):

Jennifer Leigh ◽

Mandy Rickard ◽

Stephanie Sanger ◽

Joanne Petropoulos ◽

Luis H. Braga ◽

...

Keyword(s):

Systematic Review ◽

Urinary Tract ◽

Antibiotic Prophylaxis ◽

Vesicoureteral Reflux ◽

Urinary Tract Infections ◽

First Year ◽

Antenatal Hydronephrosis ◽

Tract Infections ◽

First Year Of Life

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The role of voiding cystourethrography in the investigation of children with urinary tract infections

Canadian Urological Association Journal ◽

10.5489/cuaj.3610 ◽

2016 ◽

Vol 10 (5-6) ◽

pp. 210 ◽

Cited By ~ 5

Author(s):

Linda C. Lee ◽

Armando J. Lorenzo ◽

Martin A. Koyle

Keyword(s):

Urinary Tract ◽

Vesicoureteral Reflux ◽

Urinary Tract Infections ◽

Renal Scarring ◽

High Rate ◽

Voiding Cystourethrography ◽

Low Grade ◽

Endoscopic Injection ◽

Febrile Uti ◽

Tract Infections

Urinary tract infections (UTIs) represent a common bacterial cause of febrile illness in children. Of children presenting with a febrile UTI, 25‒40% are found to have vesicoureteral reflux (VUR). Historically, the concern regarding VUR was that it could lead to recurrent pyelonephritis, renal scarring, hypertension, and chronic kidney disease. As a result, many children underwent invasive surgical procedures to correct VUR. We now know that many cases of VUR are low-grade and have a high rate of spontaneous resolution. The roles of surveillance, antibiotic prophylaxis, endoscopic injection, and ureteral reimplantation surgery also continue to evolve. In turn, these factors have influenced the investigation of febrile UTIs.Voiding cystourethrography (VCUG) is the radiographic test of choice to diagnose VUR. Due to its invasive nature and questionable benefit in many cases, the American Academy of Pediatrics (AAP) no longer recommends VCUG routinely after an initial febrile UTI. Nevertheless, these guidelines pre-date the landmark Randomized Intervention of Children with Vesicoureteral Reflux (RIVUR) trial and there continues to be controversy regarding the diagnosis and management of VUR. This paper discusses the current literature regarding radiographic testing in children with febrile UTIs and presents a practical risk-based approach for deciding when to obtain a VCUG.

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