Antimicrobial prophylaxis for children with vesicoureteral reflux

Alejandro Hoberman, Saul P. Greenfield, Tej K. Mattoo, Ron Keren, Ranjiv Mathews, Hans G. Pohl, Bradley P. Kropp, Steven J. Skoog, Caleb P. Nelson, Marva Moxey-Mims, Russell W. Chesney, Myra A. Carpenter

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Children with febrile urinary tract infection commonly have vesicoureteral reflux. Because trial results have been limited and inconsistent, the use of antimicrobial prophylaxis to prevent recurrences in children with reflux remains controversial. METHODS: In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infection, we evaluated the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance. RESULTS: Recurrent urinary tract infection developed in 39 of 302 children who received prophylaxis as compared with 72 of 305 children who received placebo (relative risk, 0.55; 95% confidence interval [CI], 0.38 to 0.78). Prophylaxis reduced the risk of recurrences by 50% (hazard ratio, 0.50; 95% CI, 0.34 to 0.74) and was particularly effective in children whose index infection was febrile (hazard ratio, 0.41; 95% CI, 0.26 to 0.64) and in those with baseline bladder and bowel dysfunction (hazard ratio, 0.21; 95% CI, 0.08 to 0.58). The occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups (11.9% and 10.2%, respectively). Among 87 children with a first recurrence caused by Escherichia coli, the proportion of isolates that were resistant to trimethoprim-sulfamethoxazole was 63% in the prophylaxis group and 19% in the placebo group. CONCLUSIONS: Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring.

Original languageEnglish (US)
Pages (from-to)2367-2376
Number of pages10
JournalNew England Journal of Medicine
Volume370
Issue number25
DOIs
StatePublished - 2014

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Vesico-Ureteral Reflux
Recurrence
Urinary Tract Infections
Cicatrix
Placebos
Confidence Intervals
Fever
Sulfamethoxazole Drug Combination Trimethoprim
Kidney
Treatment Failure
Urinary Bladder
Randomized Controlled Trials
Escherichia coli
Infection

ASJC Scopus subject areas

  • Medicine(all)

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Hoberman, A., Greenfield, S. P., Mattoo, T. K., Keren, R., Mathews, R., Pohl, H. G., ... Carpenter, M. A. (2014). Antimicrobial prophylaxis for children with vesicoureteral reflux. New England Journal of Medicine, 370(25), 2367-2376. https://doi.org/10.1056/NEJMoa1401811

Antimicrobial prophylaxis for children with vesicoureteral reflux. / Hoberman, Alejandro; Greenfield, Saul P.; Mattoo, Tej K.; Keren, Ron; Mathews, Ranjiv; Pohl, Hans G.; Kropp, Bradley P.; Skoog, Steven J.; Nelson, Caleb P.; Moxey-Mims, Marva; Chesney, Russell W.; Carpenter, Myra A.

In: New England Journal of Medicine, Vol. 370, No. 25, 2014, p. 2367-2376.

Research output: Contribution to journalArticle

Hoberman, A, Greenfield, SP, Mattoo, TK, Keren, R, Mathews, R, Pohl, HG, Kropp, BP, Skoog, SJ, Nelson, CP, Moxey-Mims, M, Chesney, RW & Carpenter, MA 2014, 'Antimicrobial prophylaxis for children with vesicoureteral reflux', New England Journal of Medicine, vol. 370, no. 25, pp. 2367-2376. https://doi.org/10.1056/NEJMoa1401811
Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews R, Pohl HG et al. Antimicrobial prophylaxis for children with vesicoureteral reflux. New England Journal of Medicine. 2014;370(25):2367-2376. https://doi.org/10.1056/NEJMoa1401811
Hoberman, Alejandro ; Greenfield, Saul P. ; Mattoo, Tej K. ; Keren, Ron ; Mathews, Ranjiv ; Pohl, Hans G. ; Kropp, Bradley P. ; Skoog, Steven J. ; Nelson, Caleb P. ; Moxey-Mims, Marva ; Chesney, Russell W. ; Carpenter, Myra A. / Antimicrobial prophylaxis for children with vesicoureteral reflux. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 25. pp. 2367-2376.
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abstract = "BACKGROUND: Children with febrile urinary tract infection commonly have vesicoureteral reflux. Because trial results have been limited and inconsistent, the use of antimicrobial prophylaxis to prevent recurrences in children with reflux remains controversial. METHODS: In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infection, we evaluated the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance. RESULTS: Recurrent urinary tract infection developed in 39 of 302 children who received prophylaxis as compared with 72 of 305 children who received placebo (relative risk, 0.55; 95{\%} confidence interval [CI], 0.38 to 0.78). Prophylaxis reduced the risk of recurrences by 50{\%} (hazard ratio, 0.50; 95{\%} CI, 0.34 to 0.74) and was particularly effective in children whose index infection was febrile (hazard ratio, 0.41; 95{\%} CI, 0.26 to 0.64) and in those with baseline bladder and bowel dysfunction (hazard ratio, 0.21; 95{\%} CI, 0.08 to 0.58). The occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups (11.9{\%} and 10.2{\%}, respectively). Among 87 children with a first recurrence caused by Escherichia coli, the proportion of isolates that were resistant to trimethoprim-sulfamethoxazole was 63{\%} in the prophylaxis group and 19{\%} in the placebo group. CONCLUSIONS: Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring.",
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T1 - Antimicrobial prophylaxis for children with vesicoureteral reflux

AU - Hoberman, Alejandro

AU - Greenfield, Saul P.

AU - Mattoo, Tej K.

AU - Keren, Ron

AU - Mathews, Ranjiv

AU - Pohl, Hans G.

AU - Kropp, Bradley P.

AU - Skoog, Steven J.

AU - Nelson, Caleb P.

AU - Moxey-Mims, Marva

AU - Chesney, Russell W.

AU - Carpenter, Myra A.

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Children with febrile urinary tract infection commonly have vesicoureteral reflux. Because trial results have been limited and inconsistent, the use of antimicrobial prophylaxis to prevent recurrences in children with reflux remains controversial. METHODS: In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infection, we evaluated the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance. RESULTS: Recurrent urinary tract infection developed in 39 of 302 children who received prophylaxis as compared with 72 of 305 children who received placebo (relative risk, 0.55; 95% confidence interval [CI], 0.38 to 0.78). Prophylaxis reduced the risk of recurrences by 50% (hazard ratio, 0.50; 95% CI, 0.34 to 0.74) and was particularly effective in children whose index infection was febrile (hazard ratio, 0.41; 95% CI, 0.26 to 0.64) and in those with baseline bladder and bowel dysfunction (hazard ratio, 0.21; 95% CI, 0.08 to 0.58). The occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups (11.9% and 10.2%, respectively). Among 87 children with a first recurrence caused by Escherichia coli, the proportion of isolates that were resistant to trimethoprim-sulfamethoxazole was 63% in the prophylaxis group and 19% in the placebo group. CONCLUSIONS: Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring.

AB - BACKGROUND: Children with febrile urinary tract infection commonly have vesicoureteral reflux. Because trial results have been limited and inconsistent, the use of antimicrobial prophylaxis to prevent recurrences in children with reflux remains controversial. METHODS: In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infection, we evaluated the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance. RESULTS: Recurrent urinary tract infection developed in 39 of 302 children who received prophylaxis as compared with 72 of 305 children who received placebo (relative risk, 0.55; 95% confidence interval [CI], 0.38 to 0.78). Prophylaxis reduced the risk of recurrences by 50% (hazard ratio, 0.50; 95% CI, 0.34 to 0.74) and was particularly effective in children whose index infection was febrile (hazard ratio, 0.41; 95% CI, 0.26 to 0.64) and in those with baseline bladder and bowel dysfunction (hazard ratio, 0.21; 95% CI, 0.08 to 0.58). The occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups (11.9% and 10.2%, respectively). Among 87 children with a first recurrence caused by Escherichia coli, the proportion of isolates that were resistant to trimethoprim-sulfamethoxazole was 63% in the prophylaxis group and 19% in the placebo group. CONCLUSIONS: Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring.

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