Richard W.

Grady, MD

Antibiotic Prophylaxis in the Management of Vesicoureteral Reux

Rousey-Kesler G, Gadjos V, Indres N, et al.: Antibiotic
prophylaxis for the prevention of recurrent urinary
tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized
study. J Urol 2008, 179:674679.

Further studies may demonstrate that antibiotic prophylaxis is effective for more selective patient populations
such as children with high-grade VUR, in neonates, or, as
suggested by this study, boys with grade III VUR.

Rating: Of importance.

Comments

Introduction: Antibiotic prophylaxis remains a standard

form of treatment in children to prevent recurrent urinary
tract infection (UTI). It is frequently used following the
diagnosis of vesicoureteral reflux (VUR) in an effort to
reduce the incidence of UTI in this setting in which children are at increased risk of pyelonephritis.
Aims: The authors designed this study to answer the
question whether low-dose antibiotic prophylaxis using
a sulfa-based antibiotic reduces the incidence of UTI in
young children with low-grade VUR.
Methods: The authors designed this trial as a randomized, unblinded multicenter study with 225 children
from 1 month to 3 years of age followed for 18 months.
Children received daily cotrimoxazole or no treatment
and were screened for UTI using a monthly dipstick urinalysis and evaluated to see if they developed symptoms
or signs consistent with a UTI. A urinary tract infection
constituted exit from the study. Analysis was performed
using intention to treat, and UTI rates were compared
using the log rank test.
Results: The study found no significant difference of
UTI incidence between the two groups, for either UTI
in aggregate incidence or febrile incidence. Subgroup
analysis demonstrated a positive treatment effect of antibiotic prophylaxis in boys diagnosed with grade III VUR.
Antibiotic resistance also varied between the two groups,
with 27% versus 62% sensitivity to cotrimoxazole noted
between the control and treatment groups.
Discussion: The study results show that standard treatment
with antibiotic prophylaxis may be essentially ineffective
to prevent UTI in young children. Because many of the
children diagnosed with UTI and VUR are found in this
age group, these results have important implications for
our current treatment strategies of pediatric UTI and
VUR. The authors acknowledge that adherence to treatment was not measured and may have affected the results.

This multicenter study addresses a hotly debated topic

in pediatricsnamely, the use of antibiotic prophylaxis
to prevent recurrent UTI in children with VUR. The
authors selected a patient population that constitutes the
majority of children we treat with UTI and VUR. Several other studies have recently evaluated other aspects
of this same topic [14]. The ongoing National Institutes
of Healthsponsored RIVUR (Randomized Intervention for Children With Vesicoureteral Reflux) study also
seeks to address the utility of antibiotic prophylaxis for
children with VUR [5]. Whether antibiotic prophylaxis
was ineffective in this study because of poor adherence
to therapy, increased bacterial resistance to standard
antibiotics used in prophylaxis such as sulfa-based antibiotics, or some other reason, it was found to be less
effective than most would have hoped. However, before
we abandon antibiotic prophylaxis, it will be important
to determine whether some select patient groups may
benefit from this form of therapy. Ultimately, if antibiotic prophylaxis proves uniformly ineffective, treatment
paradigms will change for VUR and we may fi nd ourselves reconsidering early surgical intervention for those
children with VUR who are at increased risk of renal
damage and tailoring evaluation protocols to avoid overtreating children who will not benefit from therapeutic
intervention for VUR.

Acknowledgment
Dr. Richard W. Grady is an Associate Professor at the
Department of Urology, University of Washington School
of Medicine. He is also the Director of Clinical Research
at the Division of Pediatric Urology, Seattle Childrens
Hospital. Correspondence can be sent to 4800 Sandpoint
Way, NE, Seattle, WA 98105, USA; e-mail: richard.
grady@seattlechildrens.org.

Disclosure
Dr. Grady is an advisory board member and clinical
investigator for Q-Med, Inc.

Clinical Trials Report

References
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Cooper CS, Chung BI, Kirsch AJ, et al.: The outcome of

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Conway PH, Cnaan A, Zaoutis T, et al.: Recurrent urinary
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Cheng CH, Tsai MH, Huang YC, et al.: Antibiotic resistance
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children with vesicoureteral reflux receiving prophylactic
antibiotic therapy. Pediatrics 2008, 122:12121217.

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Hajibagheri K, Priesemann M, Morrison I, et al.: NICE guidance on urinary tract infection in children abandons routine
antibiotic prophylaxis. Arch Dis Child 2008, 93:356.
Greenfield SP, Chesney RW, Carpenter M, et al.: Vesicoureteral reflux: the RIVUR study and the way forward. J Urol
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