[Source: The Lancet Infect Dis., full page: (LINK). Abstract, edited.]
The Lancet Infectious Diseases, Early Online Publication, 19 December 2012
Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial
Prof Paul Little FRCGP a, Beth Stuart PhD a, Michael Moore FRCGP a, Prof Samuel Coenen DMSc b, Prof Christopher C Butler FRCGP d, Prof Maciek Godycki-Cwirko PhD f, Prof Artur Mierzecki PhD g, Slawomir Chlabicz PhD h, Prof Antoni Torres PhD i j, Jordi Almirall MD k l, Mel Davies MSc m, Tom Schaberg PhD n, Prof Sigvard Mölstad PhD o p, Prof Francesco Blasi MD q, An De Sutter PhD r, Prof Janko Kersnik PhD s, Helena Hupkova PhD t, Pia Touboul MD u, Prof Kerenza Hood PhD e, Mark Mullee MSc a, Gilly O'Reilly PhD a, Curt Brugman MSc v, Prof Herman Goossens PhD c, Prof Theo Verheij PhD v, on behalf of the GRACE consortium
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.
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).
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).
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.
European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders.
a Primary Care and Population Sciences Division, University of Southampton, Southampton, UK; b Centre for General Practice, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; c Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; d Cochrane Institutes of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UK; e South East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UK; f Department of Family and Community Medicine, Medical University of Łódź, Łódź, Poland; g Independent Laboratory of Family Physician Education, Pomeranian Medical University, Szczecin, Poland; h Department of Family Medicine and Community Nursing, Medical University of Bialystok, Bialystok, Poland; i Pneumology Department, Clinic Institute of Thorax, Hospital Clinic of Barcelona, Barcelona, Spain; j Insitut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona—Ciber de Enfermedades Respiratorias (Ciberes), Barcelona, Spain; k Unitat de Cures Intensives, Hospital de Mataró, Mataró, Spain; l University of Barcelona—Ciber de Enfermedades Respiratorias (Ciberes), Barcelona, Spain; m Ely Bridge Surgery, Ely, Cardiff, UK; n Zentrum für Pneumologie, Diakoniekrankenhaus, Rotenburg, Germany; o Department of Clinical Sciences, General Practice SUS, CRC Malmö, Malmö, Sweden; p Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; q Department of Pathophysiology and Transplantation, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico Cà Granda Milano, Milan, Italy; r Department of Family Practice and Primary Health Care, Hyemans Institute of Pharmacology, Ghent University, Ghent, Belgium; s OZG ZD Jesenice & Department of Family Medicine, University Ljubljana, Ljubljana, Slovenia; t Comenius University, Bratislava, Slovakia; u Department of Public Health, Nice University Hospital, Nice, France; v Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands
Correspondence to: Prof Paul Little, Aldermoor Health Centre, Aldermoor Close, Southampton SO16 5ST, UK