title: Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial.
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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders.
authors.affiliation: Primary Care and Population Sciences Division, University of Southampton, Southampton, UK. p.little@soton.ac.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Little
authors.forename: Beth
authors.initials: B
authors.lastname: Stuart
authors.forename: Michael
authors.initials: M
authors.lastname: Moore
authors.forename: Samuel
authors.initials: S
authors.lastname: Coenen
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Butler
authors.forename: Maciek
authors.initials: M
authors.lastname: Godycki-Cwirko
authors.forename: Artur
authors.initials: A
authors.lastname: Mierzecki
authors.forename: Slawomir
authors.initials: S
authors.lastname: Chlabicz
authors.forename: Antoni
authors.initials: A
authors.lastname: Torres
authors.forename: Jordi
authors.initials: J
authors.lastname: Almirall
authors.forename: Mel
authors.initials: M
authors.lastname: Davies
authors.forename: Tom
authors.initials: T
authors.lastname: Schaberg
authors.forename: Sigvard
authors.initials: S
authors.lastname: Mölstad
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.forename: An
authors.initials: A
authors.lastname: De Sutter
authors.forename: Janko
authors.initials: J
authors.lastname: Kersnik
authors.forename: Helena
authors.initials: H
authors.lastname: Hupkova
authors.forename: Pia
authors.initials: P
authors.lastname: Touboul
authors.forename: Kerenza
authors.initials: K
authors.lastname: Hood
authors.forename: Mark
authors.initials: M
authors.lastname: Mullee
authors.forename: Gilly
authors.initials: G
authors.lastname: O'Reilly
authors.forename: Curt
authors.initials: C
authors.lastname: Brugman
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.forename: Theo
authors.initials: T
authors.lastname: Verheij
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016001:Confidence Intervals; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011320:Primary Health Care; D016016:Proportional Hazards Models; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D000658:Amoxicillin