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Variation in antibiotic prescribing and its impact on recovery in patients with acute cough in primary care: prospective study in 13 countries

BMJ 2009; 338 doi: (Published 24 June 2009) Cite this as: BMJ 2009;338:b2242
  1. C C Butler, professor1,
  2. K Hood, director2,
  3. T Verheij, professor3,
  4. P Little, professor4,
  5. H Melbye, professor5,
  6. J Nuttall, senior trial manager2,
  7. M J Kelly, statistician2,
  8. S Mölstad, professor6,
  9. M Godycki-Cwirko, physician7,
  10. J Almirall, professor8,
  11. A Torres, professor9,
  12. D Gillespie, trainee statistician2,
  13. U Rautakorpi, senior medical officer10,
  14. S Coenen, postdoctoral fellow1112,
  15. H Goossens, professor13
  1. 1Department of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff CF14 4XN, Wales
  2. 2South East Wales Trials Unit (SEWTU), Department of Primary Care and Public Health, School of Medicine, Cardiff University, Heath Park, Cardiff, Wales
  3. 3University Medical Centre Utrecht, Julius Center for Health, Sciences and Primary Care, Universiteitsweg 100, Stratenum, 6th Floor, 6.111, 3584 CX Utrecht, Netherlands
  4. 4University of Southampton, Southampton SO16 5ST
  5. 5General Practice Research Unit, Institute of Community Medicine, University of Tromso, 9037 Tromso, Norway
  6. 6Department of Medical and Health Sciences, Linkoping University, and Unit of Research and Development in Primary Care, S-55185 Jonkoping, Sweden
  7. 7Department of Family and Community Medicine, Medical University of Lodz, U190-153 Lodz.Kopcinskiego 20, Poland
  8. 8Unitat de Cures Intensives, Hospital de Mataro, Carretera de Cirera s/n, 08304 Mataro (Barcelona), Spain
  9. 9Servei de Pneumologia i Al·lèrgia Respiratòria, Institut Clínic del Tòrax, Hospital Clínic de Barcelona, CIBERES 06/06/0028, Universitat de Barcelona, Spain
  10. 10Finnish Office for Health Technology Assessment, FinOHTA, Stakes Tampere Satellite Office, Fin-Medi 3, Biokatu 10, 7. krs, 33520 Tampere, Finland
  11. 11University of Antwerp-Campus Drie Eiken, Vaccine and Infectious Disease Institute, Centre for General Practice, Antwerp, Belgium
  12. 12Research Foundation, Flanders, Brussels, Belgium.
  13. 13University of Antwerp-Campus Drie Eiken, Vaccine and Infectious Disease Institute-Laboratory of Medical Microbiology, Antwerp, Belgium
  1. Correspondence to: C Butler ButlerCC{at}
  • Accepted 13 February 2009


Objective To describe variation in antibiotic prescribing for acute cough in contrasting European settings and the impact on recovery.

Design Cross sectional observational study with clinicians from 14 primary care research networks in 13 European countries who recorded symptoms on presentation and management. Patients followed up for 28 days with patient diaries.

Setting Primary care.

Participants Adults with a new or worsening cough or clinical presentation suggestive of lower respiratory tract infection.

Main outcome measures Prescribing of antibiotics by clinicians and total symptom severity scores over time.

Results 3402 patients were recruited (clinicians completed a case report form for 99% (3368) of participants and 80% (2714) returned a symptom diary). Mean symptom severity scores at presentation ranged from 19 (scale range 0 to 100) in networks based in Spain and Italy to 38 in the network based in Sweden. Antibiotic prescribing by networks ranged from 20% to nearly 90% (53% overall), with wide variation in classes of antibiotics prescribed. Amoxicillin was overall the most common antibiotic prescribed, but this ranged from 3% of antibiotics prescribed in the Norwegian network to 83% in the English network. While fluoroquinolones were not prescribed at all in three networks, they were prescribed for 18% in the Milan network. After adjustment for clinical presentation and demographics, considerable differences remained in antibiotic prescribing, ranging from Norway (odds ratio 0.18, 95% confidence interval 0.11 to 0.30) to Slovakia (11.2, 6.20 to 20.27) compared with the overall mean (proportion prescribed: 0.53). The rate of recovery was similar for patients who were and were not prescribed antibiotics (coefficient −0.01, P<0.01) once clinical presentation was taken into account.

Conclusions Variation in clinical presentation does not explain the considerable variation in antibiotic prescribing for acute cough in Europe. Variation in antibiotic prescribing is not associated with clinically important differences in recovery.

Trial registration NCT00353951.


  • We acknowledge the entire GRACE team for their diligence, expertise, and enthusiasm. The GRACE team are: Zseraldina Arvai, Zuzana Bielicka, Francesco Blasi, Alicia Borras, Curt Brugman, Jo Coast, Mel Davies, Kristien Dirven, Peter Edwards, Iris Hering, Judit Holczerné, Helena Hupkova, Kristin Alise Jakobsen, Bernadette Kovaks, Chrisina Lannering, Frank Leus, Katherine Loens, Michael Moore, Magdalena Muras, Carol Pascoe, Tom Schaberg, Matteu Serra, Richard Smith, Jackie Swain, Paolo Tarsia, Kirsi Valve, Robert Veen, and Tricia Worby. We thank all the clinicians and patients who consented to be part of GRACE, without whom this study would not have been possible.

  • Contributors: All authors contributed to either the conception and design or the analysis and interpretation of the data; contributed to drafting and revising the manuscript; and approved the final version of the manuscript. CCB is guarantor.

  • Funding: This study was funded by 6th Framework Programme of the European Commission (LSHM-CT-2005-518226). The South East Wales Trials Unit is funded by the Wales Office for Research and Development. All authors declare that they are independent of the funders.

  • Competing interests: None declared.

  • Ethical approval: Ethic review committees in each country approved the study.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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