title: Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial.
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.
  
  
  BACKGROUND
  clinicaltrials.gov (NCT01398072).
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Simon E
authors.initials: SE
authors.lastname: Brill
authors.affiliation: Medical Research Council Biostatistics Unit Hub for Trials Methodology Research, Cambridge, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Law
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Ethaar
authors.initials: E
authors.lastname: El-Emir
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Allinson
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Phillip
authors.initials: P
authors.lastname: James
authors.affiliation: Centre for Clinical Microbiology, University College London, London, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Maddox
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Gavin C
authors.initials: GC
authors.lastname: Donaldson
authors.affiliation: Centre for Clinical Microbiology, University College London, London, UK.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: McHugh
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: William O
authors.initials: WO
authors.lastname: Cookson
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Moffatt
authors.affiliation: Department of Primary Care and Population Sciences, University College London, London, UK.
authors.forename: Irwin
authors.initials: I
authors.lastname: Nazareth
authors.affiliation: Centre for Respiratory Medicine, University College London, London, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Hurst
authors.affiliation: School of Aging and Chronic Disease, University of Liverpool, Liverpool, UK.
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Calverley
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sweeting
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Jadwiga A
authors.initials: JA
authors.lastname: Wedzicha
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D058491:Bacterial Load; D004318:Doxycycline / Q000627:therapeutic use*; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D017063:Outcome Assessment, Health Care; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000382:microbiology*; D012137:Respiratory System / Q000382:microbiology*; D016037:Single-Blind Method; D013183:Sputum / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D017963:Azithromycin; D004318:Doxycycline; D000077266:Moxifloxacin
keywords: COPD Exacerbations; COPD Pathology; Respiratory Infection