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PICKET
Antibiotic prophylaxis reduced symptomatic urinary tract infection in children with vesicoureteral reflux, but not scarring
Table 1 Antibiotic prophylaxis effectiveness Outcome
COMMENTARY
STUDY QUESTION Setting: Nineteen sites in a variety of clinical settings in the USA. Patients: Six hundred and seven children, 2–71 months old, with vesicoureteral reflux (VUR) grades I–IV, recruited after their first or second urinary tract infection (UTI). Intervention: Patients received either 3 mg/kg trimethoprim plus 15 mg/kg of sulfamethoxazole daily or an identical placebo. Outcomes: Primary outcomes were febrile or symptomatic recurrence of UTI. Urinary samples were collected by catheterisation, suprapubic aspiration, or clean catch. Secondary outcomes were renal scarring diagnosed by DMSA, antibiotic resistance, and a composite outcome of treatment failure. Follow-up period: Patients were followed for 2 years. All 607 children were analysed, but 76 in the intervention group and 91 in the control group
T
his is a long overdue trial. The efficacy of antibiotic prophylaxis for children at risk of recurrent UTIs appeared dubious in previous systematic reviews.1–3 Prophylaxis seemed to reduce positive urine cultures, but not symptomatic UTIs or renal scarring. With this new, well-conducted trial, we have some answers, but still have questions. The authors of this randomised controlled trial were careful to avoid the methodological shortcomings of previous studies. It has adequate allocation concealment and blinding. Urine samples were taken by catheter or clean catch, not by bags. The follow up for 2 years was appropriate. And they looked at relevant outcomes (eg, symptomatic infections instead of asymptomatic bacteriuria). Results are both encouraging and disappointing. On the one hand, prophylaxis reduces symptomatic UTI recurrence in children with VUR by 12%. This is good news. On the other hand, prophylaxis did not reduce renal scarring, hospitalisations or emergency room visits. Also, as would be expected, there was increased antimicrobial resistance in the
52
27/227 (11.9)
24/235 (10.2)
1.7 (−4.0 to 7.4)
26/38 (68.4) Antimicrobial resistance, any pathogen UTI, urinary tract infection.
17/69 (24.6)
43.8 (25.8 to 61.7)
discontinued treatment. Another 24 and 25 children had inconclusive intervention status in the intervention and control groups, respectively. Main results: Antibiotic prophylaxis reduced the risk of recurrence by 11.9% (NNT=9, 95% CI 5 to 20). No differences were noted in renal scarring. Prophylaxis more than doubled the risk of antibiotic resistance (number needed to harm=2, 95% CI 1 to 4). Hospitalisations and side effects did not differ significantly between groups (table 1). Conclusion: Antibiotic prophylaxis reduced the risk of febrile symptomatic UTI recurrence without affecting renal scarring or hospitalisations, and increased antimicrobial resistance.
Abstracted from Hoberman A, Greenfield SP, Mattoo TK, et al. The RIVUR Trial Investigators. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med 2014;370:2367–76.
prophylaxis group: there would be 44 resistant infections more for every 100 patients treated with prophylaxis when compared to placebo (risk difference 43.8%, 95% CI 25.8 to 61.7). Another problem is that almost a third of the patients in each group either discontinued the intervention or had inconclusive status. This is not surprising, and highlights the practical difficulties of trying to give medicine to children for such a long time. Finally, the fundamental reason behind preventing UTIs is to preserve renal function. If prophylaxis does not reduce hospitalisations or renal scarring, then it would be very important to know if, in the long term, older children or adults who received prophylaxis have better kidneys. Giordano Pérez-Gaxiola Evidence-based Medicine, Hospital Pediátrico de Sinaloa, Culiacan, Mexico
Competing interests None. Provenance and peer review Not commissioned; internally peer reviewed.
Risk difference (95% CI)
Recurrent febrile 77/302 (25.5) 114/305 (37.4) −11.9 (−4.6 to −19.2) or symptomatic UTI Renal scarring
Design: Randomised controlled trial. Allocation: Computer-generated permuted block stratified randomisation done by a centralised datacoordinating centre. Blinding: Caregivers as well as physicians were blinded.
Prophylaxis Placebo n/total (%) n/total (%)
To cite Pérez-Gaxiola G. Arch Dis Child Educ Pract Ed 2015;100:52.
REFERENCES 1 Dai B, Liu Y, Jia J, et al. Long-term antibiotics for the prevention of recurrent urinary tract infection in children: a systematic review and meta-analysis. Arch Dis Child 2010;95:499–508. 2 Perez-Gaxiola G. Review: antibiotic prophylaxis may not prevent recurrent symptomatic urinary tract infection in children. Arch Dis Child Educ Pract Ed 2011;96:16–18. 3 Williams G, Craig JC. Long-term antibiotics for preventing recurrent urinary
Pérez-Gaxiola G. Arch Dis Child Educ Pract Ed 2015;100:52. doi:10.1136/archdischild-2014-307056
Downloaded from http://ep.bmj.com/ on January 22, 2015 - Published by group.bmj.com
Antibiotic prophylaxis reduced symptomatic urinary tract infection in children with vesicoureteral reflux, but not scarring Arch Dis Child Educ Pract Ed 2015 100: 52 originally published online July 29, 2014
doi: 10.1136/archdischild-2014-307056 Updated information and services can be found at: http://ep.bmj.com/content/100/1/52
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This article cites 3 articles, 1 of which you can access for free at: http://ep.bmj.com/content/100/1/52#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections Drugs: infectious diseases (96) Child health (277) Urinary tract infections (11) Urinary tract infections (11) Urology (33) Clinical trials (epidemiology) (49) Competing interests (ethics) (38) Journalology (47)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
PICKET
Antibiotic prophylaxis reduced symptomatic urinary tract infection in children with vesicoureteral reflux, but not scarring
Table 1 Antibiotic prophylaxis effectiveness Outcome
COMMENTARY
STUDY QUESTION Setting: Nineteen sites in a variety of clinical settings in the USA. Patients: Six hundred and seven children, 2–71 months old, with vesicoureteral reflux (VUR) grades I–IV, recruited after their first or second urinary tract infection (UTI). Intervention: Patients received either 3 mg/kg trimethoprim plus 15 mg/kg of sulfamethoxazole daily or an identical placebo. Outcomes: Primary outcomes were febrile or symptomatic recurrence of UTI. Urinary samples were collected by catheterisation, suprapubic aspiration, or clean catch. Secondary outcomes were renal scarring diagnosed by DMSA, antibiotic resistance, and a composite outcome of treatment failure. Follow-up period: Patients were followed for 2 years. All 607 children were analysed, but 76 in the intervention group and 91 in the control group
T
his is a long overdue trial. The efficacy of antibiotic prophylaxis for children at risk of recurrent UTIs appeared dubious in previous systematic reviews.1–3 Prophylaxis seemed to reduce positive urine cultures, but not symptomatic UTIs or renal scarring. With this new, well-conducted trial, we have some answers, but still have questions. The authors of this randomised controlled trial were careful to avoid the methodological shortcomings of previous studies. It has adequate allocation concealment and blinding. Urine samples were taken by catheter or clean catch, not by bags. The follow up for 2 years was appropriate. And they looked at relevant outcomes (eg, symptomatic infections instead of asymptomatic bacteriuria). Results are both encouraging and disappointing. On the one hand, prophylaxis reduces symptomatic UTI recurrence in children with VUR by 12%. This is good news. On the other hand, prophylaxis did not reduce renal scarring, hospitalisations or emergency room visits. Also, as would be expected, there was increased antimicrobial resistance in the
52
27/227 (11.9)
24/235 (10.2)
1.7 (−4.0 to 7.4)
26/38 (68.4) Antimicrobial resistance, any pathogen UTI, urinary tract infection.
17/69 (24.6)
43.8 (25.8 to 61.7)
discontinued treatment. Another 24 and 25 children had inconclusive intervention status in the intervention and control groups, respectively. Main results: Antibiotic prophylaxis reduced the risk of recurrence by 11.9% (NNT=9, 95% CI 5 to 20). No differences were noted in renal scarring. Prophylaxis more than doubled the risk of antibiotic resistance (number needed to harm=2, 95% CI 1 to 4). Hospitalisations and side effects did not differ significantly between groups (table 1). Conclusion: Antibiotic prophylaxis reduced the risk of febrile symptomatic UTI recurrence without affecting renal scarring or hospitalisations, and increased antimicrobial resistance.
Abstracted from Hoberman A, Greenfield SP, Mattoo TK, et al. The RIVUR Trial Investigators. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med 2014;370:2367–76.
prophylaxis group: there would be 44 resistant infections more for every 100 patients treated with prophylaxis when compared to placebo (risk difference 43.8%, 95% CI 25.8 to 61.7). Another problem is that almost a third of the patients in each group either discontinued the intervention or had inconclusive status. This is not surprising, and highlights the practical difficulties of trying to give medicine to children for such a long time. Finally, the fundamental reason behind preventing UTIs is to preserve renal function. If prophylaxis does not reduce hospitalisations or renal scarring, then it would be very important to know if, in the long term, older children or adults who received prophylaxis have better kidneys. Giordano Pérez-Gaxiola Evidence-based Medicine, Hospital Pediátrico de Sinaloa, Culiacan, Mexico
Competing interests None. Provenance and peer review Not commissioned; internally peer reviewed.
Risk difference (95% CI)
Recurrent febrile 77/302 (25.5) 114/305 (37.4) −11.9 (−4.6 to −19.2) or symptomatic UTI Renal scarring
Design: Randomised controlled trial. Allocation: Computer-generated permuted block stratified randomisation done by a centralised datacoordinating centre. Blinding: Caregivers as well as physicians were blinded.
Prophylaxis Placebo n/total (%) n/total (%)
To cite Pérez-Gaxiola G. Arch Dis Child Educ Pract Ed 2015;100:52.
REFERENCES 1 Dai B, Liu Y, Jia J, et al. Long-term antibiotics for the prevention of recurrent urinary tract infection in children: a systematic review and meta-analysis. Arch Dis Child 2010;95:499–508. 2 Perez-Gaxiola G. Review: antibiotic prophylaxis may not prevent recurrent symptomatic urinary tract infection in children. Arch Dis Child Educ Pract Ed 2011;96:16–18. 3 Williams G, Craig JC. Long-term antibiotics for preventing recurrent urinary
Pérez-Gaxiola G. Arch Dis Child Educ Pract Ed 2015;100:52. doi:10.1136/archdischild-2014-307056
Downloaded from http://ep.bmj.com/ on January 22, 2015 - Published by group.bmj.com
Antibiotic prophylaxis reduced symptomatic urinary tract infection in children with vesicoureteral reflux, but not scarring Arch Dis Child Educ Pract Ed 2015 100: 52 originally published online July 29, 2014
doi: 10.1136/archdischild-2014-307056 Updated information and services can be found at: http://ep.bmj.com/content/100/1/52
These include:
References Email alerting service
Topic Collections
This article cites 3 articles, 1 of which you can access for free at: http://ep.bmj.com/content/100/1/52#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections Drugs: infectious diseases (96) Child health (277) Urinary tract infections (11) Urinary tract infections (11) Urology (33) Clinical trials (epidemiology) (49) Competing interests (ethics) (38) Journalology (47)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
