Short-course oral co-trimoxazole versus intramuscular benzathine benzylpenicillin for impetigo in a highly endemic region: an open-label, randomised, controlled, non-inferiority trial

Asha C Bowen; Steven Y C Tong; Ross M Andrews; Irene M O'Meara; Malcolm I McDonald; Mark D Chatfield; Bart J Currie; Jonathan R Carapetis

doi:10.1016/S0140-6736(14)60841-2

Short-course oral co-trimoxazole versus intramuscular benzathine benzylpenicillin for impetigo in a highly endemic region: an open-label, randomised, controlled, non-inferiority trial

Asha C Bowen, Steven Y C Tong, Ross M Andrews, Irene M O'Meara, Malcolm I McDonald, Mark D Chatfield, Bart J Currie, Jonathan R Carapetis

UWA Centre for Child Health Research (affiliated with the The Kids Research Institute Australia)

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Abstract

BACKGROUND: Impetigo affects more than 110 million children worldwide at any one time. The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial resistance. Few trials of systemic antibiotics are available to guide management of extensive impetigo. As such, we aimed to compare short-course oral co-trimoxazole with standard treatment with intramuscular benzathine benzylpenicillin in children with impetigo in a highly endemic setting.

METHODS: In this randomised, controlled, non-inferiority trial, Indigenous Australian children aged 3 months to 13 years with purulent or crusted non-bullous impetigo were randomly assigned (1:1:1) to receive benzathine benzylpenicillin (weight-banded injection), twice-daily co-trimoxazole for 3 days (4 mg/kg plus 20 mg/kg per dose), or once-daily co-trimoxazole for 5 days (8 mg/kg plus 40 mg/kg per dose). At every visit, participants were randomised in blocks of six and 12, stratified by disease severity. Randomisation was done by research nurses and codes were in sealed, sequentially numbered, opaque envelopes. Independent reviewers masked to treatment allocation compared digital images of sores from days 0 and 7. The primary outcome was treatment success at day 7 in a modified intention-to-treat analysis. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000858291.

FINDINGS: Between Nov 26, 2009, and Nov 20, 2012, 508 patients were randomly assigned to receive benzathine benzylpenicillin (n=165 [156 analysed]), twice-daily co-trimoxazole for 3 days (n=175 [173 analysed]), or once-daily co-trimoxazole for 5 days (n=168 [161 analysed]). Treatment was successful in 133 (85%) children who received benzathine benzylpenicillin and 283 (85%) who received pooled co-trimoxazole (absolute difference 0·5%; 95% CI -6·2 to 7·3), showing non-inferiority of co-trimoxazole (10% margin). Results for twice-daily co-trimoxazole for 3 days and once-daily co-trimoxazole for 5 days were similar. Adverse events occurred in 54 participants, 49 (90%) of whom received benzathine benzylpenicillin.

INTERPRETATION: Short-course co-trimoxazole is a non-inferior, alternative treatment to benzathine benzylpenicillin for impetigo; it is palatable, pain-free, practical, and easily administered.

FUNDING: Australian National Health and Medical Research Council.

Original language	English
Pages (from-to)	2132-2140
Number of pages	9
Journal	The Lancet
Volume	13-19
Issue number	9960
Early online date	26 Aug 2014
DOIs	https://doi.org/10.1016/S0140-6736(14)60841-2
Publication status	Published - 13 Dec 2014

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This is an author-submitted, peer-reviewed version of a manuscript that has been accepted for publication in the European Respiratory Journal, prior to copy-editing, formatting and typesetting. This version of the manuscript may not be duplicated or reproduced without prior permission from the copyright owner, the European Respiratory Society. The publisher is not responsible or liable for any errors or omissions in this version of the manuscript or in any version derived from it by any other parties. The final, copy-edited, published article, which is the version of record, is available without a subscription 18 months after the date of issue publication.
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Bowen, A. C., Tong, S. Y. C., Andrews, R. M., O'Meara, I. M., McDonald, M. I., Chatfield, M. D., Currie, B. J., & Carapetis, J. R. (2014). Short-course oral co-trimoxazole versus intramuscular benzathine benzylpenicillin for impetigo in a highly endemic region: an open-label, randomised, controlled, non-inferiority trial. The Lancet, 13-19(9960), 2132-2140. https://doi.org/10.1016/S0140-6736(14)60841-2

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abstract = "BACKGROUND: Impetigo affects more than 110 million children worldwide at any one time. The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial resistance. Few trials of systemic antibiotics are available to guide management of extensive impetigo. As such, we aimed to compare short-course oral co-trimoxazole with standard treatment with intramuscular benzathine benzylpenicillin in children with impetigo in a highly endemic setting.METHODS: In this randomised, controlled, non-inferiority trial, Indigenous Australian children aged 3 months to 13 years with purulent or crusted non-bullous impetigo were randomly assigned (1:1:1) to receive benzathine benzylpenicillin (weight-banded injection), twice-daily co-trimoxazole for 3 days (4 mg/kg plus 20 mg/kg per dose), or once-daily co-trimoxazole for 5 days (8 mg/kg plus 40 mg/kg per dose). At every visit, participants were randomised in blocks of six and 12, stratified by disease severity. Randomisation was done by research nurses and codes were in sealed, sequentially numbered, opaque envelopes. Independent reviewers masked to treatment allocation compared digital images of sores from days 0 and 7. The primary outcome was treatment success at day 7 in a modified intention-to-treat analysis. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000858291.FINDINGS: Between Nov 26, 2009, and Nov 20, 2012, 508 patients were randomly assigned to receive benzathine benzylpenicillin (n=165 [156 analysed]), twice-daily co-trimoxazole for 3 days (n=175 [173 analysed]), or once-daily co-trimoxazole for 5 days (n=168 [161 analysed]). Treatment was successful in 133 (85%) children who received benzathine benzylpenicillin and 283 (85%) who received pooled co-trimoxazole (absolute difference 0·5%; 95% CI -6·2 to 7·3), showing non-inferiority of co-trimoxazole (10% margin). Results for twice-daily co-trimoxazole for 3 days and once-daily co-trimoxazole for 5 days were similar. Adverse events occurred in 54 participants, 49 (90%) of whom received benzathine benzylpenicillin.INTERPRETATION: Short-course co-trimoxazole is a non-inferior, alternative treatment to benzathine benzylpenicillin for impetigo; it is palatable, pain-free, practical, and easily administered.FUNDING: Australian National Health and Medical Research Council.",

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author = "Bowen, {Asha C} and Tong, {Steven Y C} and Andrews, {Ross M} and O'Meara, {Irene M} and McDonald, {Malcolm I} and Chatfield, {Mark D} and Currie, {Bart J} and Carapetis, {Jonathan R}",

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doi = "10.1016/S0140-6736(14)60841-2",

language = "English",

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Bowen, AC, Tong, SYC, Andrews, RM, O'Meara, IM, McDonald, MI, Chatfield, MD, Currie, BJ & Carapetis, JR 2014, 'Short-course oral co-trimoxazole versus intramuscular benzathine benzylpenicillin for impetigo in a highly endemic region: an open-label, randomised, controlled, non-inferiority trial', The Lancet, vol. 13-19, no. 9960, pp. 2132-2140. https://doi.org/10.1016/S0140-6736(14)60841-2

Short-course oral co-trimoxazole versus intramuscular benzathine benzylpenicillin for impetigo in a highly endemic region: an open-label, randomised, controlled, non-inferiority trial. / Bowen, Asha C; Tong, Steven Y C; Andrews, Ross M et al.
In: The Lancet, Vol. 13-19, No. 9960, 13.12.2014, p. 2132-2140.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Short-course oral co-trimoxazole versus intramuscular benzathine benzylpenicillin for impetigo in a highly endemic region

T2 - an open-label, randomised, controlled, non-inferiority trial

AU - Bowen, Asha C

AU - Tong, Steven Y C

AU - Andrews, Ross M

AU - O'Meara, Irene M

AU - McDonald, Malcolm I

AU - Chatfield, Mark D

AU - Currie, Bart J

AU - Carapetis, Jonathan R

PY - 2014/12/13

Y1 - 2014/12/13

N2 - BACKGROUND: Impetigo affects more than 110 million children worldwide at any one time. The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial resistance. Few trials of systemic antibiotics are available to guide management of extensive impetigo. As such, we aimed to compare short-course oral co-trimoxazole with standard treatment with intramuscular benzathine benzylpenicillin in children with impetigo in a highly endemic setting.METHODS: In this randomised, controlled, non-inferiority trial, Indigenous Australian children aged 3 months to 13 years with purulent or crusted non-bullous impetigo were randomly assigned (1:1:1) to receive benzathine benzylpenicillin (weight-banded injection), twice-daily co-trimoxazole for 3 days (4 mg/kg plus 20 mg/kg per dose), or once-daily co-trimoxazole for 5 days (8 mg/kg plus 40 mg/kg per dose). At every visit, participants were randomised in blocks of six and 12, stratified by disease severity. Randomisation was done by research nurses and codes were in sealed, sequentially numbered, opaque envelopes. Independent reviewers masked to treatment allocation compared digital images of sores from days 0 and 7. The primary outcome was treatment success at day 7 in a modified intention-to-treat analysis. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000858291.FINDINGS: Between Nov 26, 2009, and Nov 20, 2012, 508 patients were randomly assigned to receive benzathine benzylpenicillin (n=165 [156 analysed]), twice-daily co-trimoxazole for 3 days (n=175 [173 analysed]), or once-daily co-trimoxazole for 5 days (n=168 [161 analysed]). Treatment was successful in 133 (85%) children who received benzathine benzylpenicillin and 283 (85%) who received pooled co-trimoxazole (absolute difference 0·5%; 95% CI -6·2 to 7·3), showing non-inferiority of co-trimoxazole (10% margin). Results for twice-daily co-trimoxazole for 3 days and once-daily co-trimoxazole for 5 days were similar. Adverse events occurred in 54 participants, 49 (90%) of whom received benzathine benzylpenicillin.INTERPRETATION: Short-course co-trimoxazole is a non-inferior, alternative treatment to benzathine benzylpenicillin for impetigo; it is palatable, pain-free, practical, and easily administered.FUNDING: Australian National Health and Medical Research Council.

AB - BACKGROUND: Impetigo affects more than 110 million children worldwide at any one time. The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial resistance. Few trials of systemic antibiotics are available to guide management of extensive impetigo. As such, we aimed to compare short-course oral co-trimoxazole with standard treatment with intramuscular benzathine benzylpenicillin in children with impetigo in a highly endemic setting.METHODS: In this randomised, controlled, non-inferiority trial, Indigenous Australian children aged 3 months to 13 years with purulent or crusted non-bullous impetigo were randomly assigned (1:1:1) to receive benzathine benzylpenicillin (weight-banded injection), twice-daily co-trimoxazole for 3 days (4 mg/kg plus 20 mg/kg per dose), or once-daily co-trimoxazole for 5 days (8 mg/kg plus 40 mg/kg per dose). At every visit, participants were randomised in blocks of six and 12, stratified by disease severity. Randomisation was done by research nurses and codes were in sealed, sequentially numbered, opaque envelopes. Independent reviewers masked to treatment allocation compared digital images of sores from days 0 and 7. The primary outcome was treatment success at day 7 in a modified intention-to-treat analysis. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000858291.FINDINGS: Between Nov 26, 2009, and Nov 20, 2012, 508 patients were randomly assigned to receive benzathine benzylpenicillin (n=165 [156 analysed]), twice-daily co-trimoxazole for 3 days (n=175 [173 analysed]), or once-daily co-trimoxazole for 5 days (n=168 [161 analysed]). Treatment was successful in 133 (85%) children who received benzathine benzylpenicillin and 283 (85%) who received pooled co-trimoxazole (absolute difference 0·5%; 95% CI -6·2 to 7·3), showing non-inferiority of co-trimoxazole (10% margin). Results for twice-daily co-trimoxazole for 3 days and once-daily co-trimoxazole for 5 days were similar. Adverse events occurred in 54 participants, 49 (90%) of whom received benzathine benzylpenicillin.INTERPRETATION: Short-course co-trimoxazole is a non-inferior, alternative treatment to benzathine benzylpenicillin for impetigo; it is palatable, pain-free, practical, and easily administered.FUNDING: Australian National Health and Medical Research Council.

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KW - Drug Administration Schedule

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KW - Humans

KW - Impetigo/drug therapy

KW - Infant

KW - Injections, Intramuscular

KW - Male

KW - Northern Territory

KW - Oceanic Ancestry Group

KW - Penicillin G Benzathine/administration & dosage

KW - Treatment Outcome

KW - Trimethoprim, Sulfamethoxazole Drug Combination/administration & dosage

U2 - 10.1016/S0140-6736(14)60841-2

DO - 10.1016/S0140-6736(14)60841-2

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VL - 13-19

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JO - The Lancet

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IS - 9960

ER -

Short-course oral co-trimoxazole versus intramuscular benzathine benzylpenicillin for impetigo in a highly endemic region: an open-label, randomised, controlled, non-inferiority trial

Abstract

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