2261. Impact of Antimicrobial Prophylaxis on the Development of Antimicrobial Resistance
Session: Poster Abstract Session: Pediatric Potpourri
Saturday, October 29, 2016
Room: Poster Hall
Background: In children with vesicoureteral reflux (VUR), antimicrobial prophylaxis reduced the rate of recurrent urinary tract infection (UTI) but not of renal scarring. We aimed to determine the impact of antimicrobial prophylaxis on colonization with antibiotic resistant Escherichia coli. Methods: On a subgroup of children enrolled in the placebo-controlled RIVUR trial at 3 of 19 participating institutions, we prospectively observed the relationship between trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis and the development of colonization by TMP-SMX resistant E. coli. Exposure to prophylaxis was by random assignment. Colonization was identified by periodic rectal swab cultures and/or urine culture for recurrent UTIs during a 24-month follow-up period. In addition to an intention-to-treat (ITT) analysis, we conducted a per-protocol analysis censoring participants after they had discontinued the assigned treatment. Results: Of 607 children in the RIVUR trial, 115 (19%) are included in the analysis. Of these, 22 (19%) of children had TMP-SMX resistant E. coli at any time during follow-up (3 of 57 children, or 5.3% assigned to placebo vs. 19 of 58 children, or 33% assigned to TMP-SMX prophylaxis). The figure shows Kaplan-Meier cumulative risk curves and the table shows the analytic results.

Analysis Method

Odds ratio

(95% CI)

p-value

Cumulative Risk difference

(95% CI)

ITT

7.6

 (2.2, 25.7)

0.001

0.33

 (0.16, 0.48)

Per-protocol

11.0

 (2.6, 47.6)

0.001

0.35

 (0.18, 0.50)

  Conclusion: Children exposed to TMP-SMX prophylaxis to prevent recurrent UTI had more than 7 times the odds of acquiring colonization with TMP-SMX resistant E. coli compared to unexposed children. The potential benefits of prophylaxis should be considered in the context of this risk for resistance.   
Jeffrey S. Gerber, MD, PhD1, Brian T. Fisher, DO, MSCE, MPH2, Rachael Ross, MPH1,3, Matthew Bryan, PhD4, Russell Localio, PhD5, Karen a Barbadora, BS, MT-ASCP6, Ron Keren, MD, MPH7, Alejandro Hoberman, MD8, Michael Green, MD, MPH, FIDSA9 and Theoklis Zaoutis, MD, MSCE10, (1)Department of Pediatrics, Division of Infectious Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA, (2)Division of Infectious Diseases, Department of Pediatrics, Center for Pediatric Clinical Effectiveness, Center for Clinical Epidemiology and Biostatistics, The Children’s Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, (3)Center for Pediatric Clinical Effectiveness, The Children's Hospital of Philadelphia, Philadelphia, PA, (4)Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, (5)Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, (6)Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, (7)Division of General Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, (8)Division of General Academic Pediatrics, University of Pittsburgh, Pittsburgh, PA, (9)Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, PA, (10)The Children's Hospital of Philadelphia, Philadelphia, PA

Disclosures:

J. S. Gerber, None

B. T. Fisher, Merck & Co.: Investigator , Research grant
Pfizer Inc.: Investigator , Research grant
Ansun BioPharma: Investigator , Research grant

R. Ross, None

M. Bryan, None

R. Localio, None

K. A. Barbadora, None

R. Keren, None

A. Hoberman, None

M. Green, None

T. Zaoutis, None

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