Downloaded from http://adc.bmj.com/ on March 7, 2015 - Published by group.bmj.com
Review
ARCHIVIST
Antibiotic prophylaxis in VUR: should we or shouldn’t we? Whether or not to give antibiotic prophylaxis to children known to have vesico-ureteric reflux (VUR) remains highly controversial. In 2007, the UK National Institute for Health and Clinical Excellence (NICE) came out against its routine use, and since then many authorities have questioned this advice, some using the pages of this journal. The evidence from published trials is contradictory and confusing. Now a new multicentre randomised controlled trial (RCT) from the US makes an important contribution to the debate (The RIVUR Trial. NEJM 2014;370:2367–76). Over 600 children (92% girls) aged 2 months to 6 years were randomised. Each had a firm diagnosis of one or two confirmed urinary tract infection (UTI): fever >38°C and/or urinary symptoms within 24 hours of urine collection; specimens were from clean catch, catheter or suprapubic aspiration only, and needed to show pyuria and a positive bacterial culture. Each had undergone voiding cysto-urethrography (VCUG), confirming VUR grades I–IV. All had radio-labelled DMSA scanning at baseline and after 1–2 years. The case group received co-trimoxazole (trimthoprim 3 mg/kg, sulphamethoxazole 15 mg/kg) daily, while the controls received a convincing placebo. Over two years of close observation for UTI, the prophylaxis group had significantly fewer proven recurrent infections (hazard ratio 0.41; 95% CI 0.34–0.74). Prophylaxis proved more effective in those whose initial infection was febrile, and in those with underlying bowel or bladder dysfunction. Unsurprisingly, the prophylaxis group had more E. coli infections that were resistant to co-trimoxazole (63% vs 19%). However, perhaps more interestingly, there was no significant difference in the incidence of DMSA-proven renal scarring at the end of the study: around 11% for both groups. An accompanying editorial highlights that this study was more rigorous than previous RCTs of prophylaxis: younger age group included, more robust UTI ascertainment, better radiology (Ingelfinger JR, Stapleton FB. NEJM 2014;370:2441). However, only one type of medication was used, and there remains the question of very long-term renal outcomes after 2 years. Also, it seems likely that parents participating in the study would have had a heightened awareness of symptoms of UTI and the need for treatment compared to parents in the real world, thus possibly making outcomes seem better in the control group. These results beg the question of why do we use prophylaxis anyway? From these data, if it’s to prevent recurrent infections, it works. If it’s to prevent scarring, it doesn’t. If prophylaxis doesn’t prevent scarring, and VUR gets better with time anyway, do we actually need to know whether VUR is present? One conclusion from this might be that we should be doing fewer VCUG examinations – as recommended by NICE. Competing interests None. Provenance and peer review Commissioned; internally peer reviewed. Accepted 4 July 2014 Published Online First 16 July 2014 Arch Dis Child 2014;99:861. doi:10.1136/archdischild-2014-307094
Taylor J, et al. Arch Dis Child 2014;99:857–861. doi:10.1136/archdischild-2013-304827
861
Downloaded from http://adc.bmj.com/ on March 7, 2015 - Published by group.bmj.com
Antibiotic prophylaxis in VUR: should we or shouldn't we? Arch Dis Child 2014 99: 861 originally published online July 16, 2014
doi: 10.1136/archdischild-2014-307094 Updated information and services can be found at: http://adc.bmj.com/content/99/9/861
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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/
Review
ARCHIVIST
Antibiotic prophylaxis in VUR: should we or shouldn’t we? Whether or not to give antibiotic prophylaxis to children known to have vesico-ureteric reflux (VUR) remains highly controversial. In 2007, the UK National Institute for Health and Clinical Excellence (NICE) came out against its routine use, and since then many authorities have questioned this advice, some using the pages of this journal. The evidence from published trials is contradictory and confusing. Now a new multicentre randomised controlled trial (RCT) from the US makes an important contribution to the debate (The RIVUR Trial. NEJM 2014;370:2367–76). Over 600 children (92% girls) aged 2 months to 6 years were randomised. Each had a firm diagnosis of one or two confirmed urinary tract infection (UTI): fever >38°C and/or urinary symptoms within 24 hours of urine collection; specimens were from clean catch, catheter or suprapubic aspiration only, and needed to show pyuria and a positive bacterial culture. Each had undergone voiding cysto-urethrography (VCUG), confirming VUR grades I–IV. All had radio-labelled DMSA scanning at baseline and after 1–2 years. The case group received co-trimoxazole (trimthoprim 3 mg/kg, sulphamethoxazole 15 mg/kg) daily, while the controls received a convincing placebo. Over two years of close observation for UTI, the prophylaxis group had significantly fewer proven recurrent infections (hazard ratio 0.41; 95% CI 0.34–0.74). Prophylaxis proved more effective in those whose initial infection was febrile, and in those with underlying bowel or bladder dysfunction. Unsurprisingly, the prophylaxis group had more E. coli infections that were resistant to co-trimoxazole (63% vs 19%). However, perhaps more interestingly, there was no significant difference in the incidence of DMSA-proven renal scarring at the end of the study: around 11% for both groups. An accompanying editorial highlights that this study was more rigorous than previous RCTs of prophylaxis: younger age group included, more robust UTI ascertainment, better radiology (Ingelfinger JR, Stapleton FB. NEJM 2014;370:2441). However, only one type of medication was used, and there remains the question of very long-term renal outcomes after 2 years. Also, it seems likely that parents participating in the study would have had a heightened awareness of symptoms of UTI and the need for treatment compared to parents in the real world, thus possibly making outcomes seem better in the control group. These results beg the question of why do we use prophylaxis anyway? From these data, if it’s to prevent recurrent infections, it works. If it’s to prevent scarring, it doesn’t. If prophylaxis doesn’t prevent scarring, and VUR gets better with time anyway, do we actually need to know whether VUR is present? One conclusion from this might be that we should be doing fewer VCUG examinations – as recommended by NICE. Competing interests None. Provenance and peer review Commissioned; internally peer reviewed. Accepted 4 July 2014 Published Online First 16 July 2014 Arch Dis Child 2014;99:861. doi:10.1136/archdischild-2014-307094
Taylor J, et al. Arch Dis Child 2014;99:857–861. doi:10.1136/archdischild-2013-304827
861
Downloaded from http://adc.bmj.com/ on March 7, 2015 - Published by group.bmj.com
Antibiotic prophylaxis in VUR: should we or shouldn't we? Arch Dis Child 2014 99: 861 originally published online July 16, 2014
doi: 10.1136/archdischild-2014-307094 Updated information and services can be found at: http://adc.bmj.com/content/99/9/861
These include:
Email alerting service
Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
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/
