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Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial

Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial
Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial
Background: Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older.

Methods: Patients older than 18 years with acute lower-respiratory-tract infections (cough of ?28 days' duration) in whom pneumonia was not suspected were randomly assigned (1:1) to either amoxicillin (1 g three times daily for 7 days) or placebo by computer-generated random numbers. Our primary outcome was duration of symptoms rated “moderately bad” or worse. Secondary outcomes were symptom severity in days 2—4 and new or worsening symptoms. Investigators and patients were masked to treatment allocation. This trial is registered with EudraCT (2007-001586-15), UKCRN Portfolio (ID 4175), ISRCTN (52261229), and FWO (G.0274.08N).

Findings: 1038 patients were assigned to the amoxicillin group and 1023 to the placebo group. Neither duration of symptoms rated “moderately bad” or worse (hazard ratio 1·06, 95% CI 0·96—1·18; p=0·229) nor mean symptom severity (1·69 with placebo vs 1·62 with amoxicillin; difference ?0·07 [95% CI ?0·15 to 0·007]; p=0·074) differed significantly between groups. New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group (162 [15·9%] of 1021 patients vs 194 [19·3%] of 1006; p=0·043; number needed to treat 30). Cases of nausea, rash, or diarrhoea were significantly more common in the amoxicillin group than in the placebo group (number needed to harm 21, 95% CI 11—174; p=0·025), and one case of anaphylaxis was noted with amoxicillin. Two patients in the placebo group and one in the amoxicillin group needed to be admitted to hospital; no study-related deaths were noted. We noted no evidence of selective benefit in patients aged 60 years or older (n=595).

Interpretation: When pneumonia is not suspected clinically, amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more, and causes slight harms.

Funding

European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders.
1473-3099
123-129
Little, Paul
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Stuart, Beth
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Moore, Michael
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Coenen, Samuel
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Butler, Christopher C.
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Godycki-Cwirko, Maciek
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Mierzecki, Artur
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Chlabicz, Slawomir
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Torres, Antoni
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Almirall, Jordi
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Davies, Mel
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Schaberg, Tom
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Molstad, Sigvard
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Blasi, Francesco
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De Sutter, An
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Kersnik, Janko
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Hupkova, Helena
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Touboul, Pia
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Hood, Kerenza
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Mullee, Mark
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O'Reilly, Gillian
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Brugman, Curt
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Goossens, Herman
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Verheij, Theo
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GRACE Consortium
Little, Paul
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Stuart, Beth
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Moore, Michael
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Coenen, Samuel
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Butler, Christopher C.
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Godycki-Cwirko, Maciek
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Mierzecki, Artur
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Chlabicz, Slawomir
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Torres, Antoni
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Almirall, Jordi
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Davies, Mel
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Schaberg, Tom
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Molstad, Sigvard
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Blasi, Francesco
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De Sutter, An
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Kersnik, Janko
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Hupkova, Helena
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Touboul, Pia
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Hood, Kerenza
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Mullee, Mark
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O'Reilly, Gillian
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Brugman, Curt
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Goossens, Herman
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Verheij, Theo
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Little, Paul, Stuart, Beth, Moore, Michael, Coenen, Samuel, Butler, Christopher C., Godycki-Cwirko, Maciek, Mierzecki, Artur, Chlabicz, Slawomir, Torres, Antoni, Almirall, Jordi, Davies, Mel, Schaberg, Tom, Molstad, Sigvard, Blasi, Francesco, De Sutter, An, Kersnik, Janko, Hupkova, Helena, Touboul, Pia, Hood, Kerenza, Mullee, Mark, O'Reilly, Gillian, Brugman, Curt, Goossens, Herman and Verheij, Theo , GRACE Consortium (2013) Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial. The Lancet Infectious Diseases, 13 (2), 123-129. (doi:10.1016/S1473-3099(12)70300-6). (PMID:23265995)

Record type: Article

Abstract

Background: Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older.

Methods: Patients older than 18 years with acute lower-respiratory-tract infections (cough of ?28 days' duration) in whom pneumonia was not suspected were randomly assigned (1:1) to either amoxicillin (1 g three times daily for 7 days) or placebo by computer-generated random numbers. Our primary outcome was duration of symptoms rated “moderately bad” or worse. Secondary outcomes were symptom severity in days 2—4 and new or worsening symptoms. Investigators and patients were masked to treatment allocation. This trial is registered with EudraCT (2007-001586-15), UKCRN Portfolio (ID 4175), ISRCTN (52261229), and FWO (G.0274.08N).

Findings: 1038 patients were assigned to the amoxicillin group and 1023 to the placebo group. Neither duration of symptoms rated “moderately bad” or worse (hazard ratio 1·06, 95% CI 0·96—1·18; p=0·229) nor mean symptom severity (1·69 with placebo vs 1·62 with amoxicillin; difference ?0·07 [95% CI ?0·15 to 0·007]; p=0·074) differed significantly between groups. New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group (162 [15·9%] of 1021 patients vs 194 [19·3%] of 1006; p=0·043; number needed to treat 30). Cases of nausea, rash, or diarrhoea were significantly more common in the amoxicillin group than in the placebo group (number needed to harm 21, 95% CI 11—174; p=0·025), and one case of anaphylaxis was noted with amoxicillin. Two patients in the placebo group and one in the amoxicillin group needed to be admitted to hospital; no study-related deaths were noted. We noted no evidence of selective benefit in patients aged 60 years or older (n=595).

Interpretation: When pneumonia is not suspected clinically, amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more, and causes slight harms.

Funding

European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders.

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e-pub ahead of print date: 19 December 2012
Published date: February 2013
Organisations: Primary Care & Population Sciences

Identifiers

Local EPrints ID: 347558
URI: https://eprints.soton.ac.uk/id/eprint/347558
ISSN: 1473-3099
PURE UUID: 9af8dc93-d503-46a9-a943-11c1ab6581de
ORCID for Michael Moore: ORCID iD orcid.org/0000-0002-5127-4509

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Date deposited: 24 Jan 2013 14:05
Last modified: 19 Nov 2019 01:46

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Contributors

Author: Paul Little
Author: Beth Stuart
Author: Michael Moore ORCID iD
Author: Samuel Coenen
Author: Christopher C. Butler
Author: Maciek Godycki-Cwirko
Author: Artur Mierzecki
Author: Slawomir Chlabicz
Author: Antoni Torres
Author: Jordi Almirall
Author: Mel Davies
Author: Tom Schaberg
Author: Sigvard Molstad
Author: Francesco Blasi
Author: An De Sutter
Author: Janko Kersnik
Author: Helena Hupkova
Author: Pia Touboul
Author: Kerenza Hood
Author: Mark Mullee
Author: Curt Brugman
Author: Herman Goossens
Author: Theo Verheij

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