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Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial
  1. Simon E Brill1,
  2. Martin Law2,
  3. Ethaar El-Emir1,
  4. James P Allinson1,
  5. Phillip James1,
  6. Victoria Maddox3,
  7. Gavin C Donaldson1,
  8. Timothy D McHugh3,
  9. William O Cookson1,
  10. Miriam F Moffatt1,
  11. Irwin Nazareth4,
  12. John R Hurst5,
  13. Peter M A Calverley6,
  14. Michael J Sweeting7,
  15. Jadwiga A Wedzicha1
  1. 1National Heart and Lung Institute, Imperial College London, London, UK
  2. 2Medical Research Council Biostatistics Unit Hub for Trials Methodology Research, Cambridge, UK
  3. 3Centre for Clinical Microbiology, University College London, London, UK
  4. 4Department of Primary Care and Population Sciences, University College London, London, UK
  5. 5Centre for Respiratory Medicine, University College London, London, UK
  6. 6School of Aging and Chronic Disease, University of Liverpool, Liverpool, UK
  7. 7Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  1. Correspondence to Dr Simon E Brill, Airway Disease Section, National Heart and Lung Institute, Guy Scadding Building, Dovehouse Street, London SW3 6LY, UK; s.brill{at}imperial.ac.uk

Abstract

Background Long-term antibiotic therapy is used to prevent exacerbations of COPD but there is uncertainty over whether this reduces airway bacteria. The optimum antibiotic choice remains unknown. We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo.

Methods This was a single-centre, single-blind, randomised placebo-controlled trial. Patients aged ≥45 years with COPD, FEV1<80% predicted and chronic productive cough were randomised to receive either moxifloxacin 400 mg daily for 5 days every 4 weeks, doxycycline 100 mg/day, azithromycin 250 mg 3 times a week or one placebo tablet daily for 13 weeks. The primary outcome was the change in total cultured bacterial load in sputum from baseline; secondary outcomes included bacterial load by 16S quantitative PCR (qPCR), sputum inflammation and antibiotic resistance.

Results 99 patients were randomised; 86 completed follow-up, were able to expectorate sputum and were analysed. After adjustment, there was a non-significant reduction in bacterial load of 0.42 log10 cfu/mL (95% CI −0.08 to 0.91, p=0.10) with moxifloxacin, 0.11 (−0.33 to 0.55, p=0.62) with doxycycline and 0.08 (−0.38 to 0.54, p=0.73) with azithromycin from placebo, respectively. There were also no significant changes in bacterial load measured by 16S qPCR or in airway inflammation. More treatment-related adverse events occurred with moxifloxacin. Of note, mean inhibitory concentrations of cultured isolates increased by at least three times over placebo in all treatment arms.

Conclusions Total airway bacterial load did not decrease significantly after 3 months of antibiotic therapy. Large increases in antibiotic resistance were seen in all treatment groups and this has important implications for future studies.

Trial registration number clinicaltrials.gov (NCT01398072).

  • COPD Exacerbations
  • COPD Pathology
  • Respiratory Infection

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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