PT  - JOURNAL ARTICLE
AU  - Simon E Brill
AU  - Martin Law
AU  - Ethaar El-Emir
AU  - James P Allinson
AU  - Phillip James
AU  - Victoria Maddox
AU  - Gavin C Donaldson
AU  - Timothy D McHugh
AU  - William O Cookson
AU  - Miriam F Moffatt
AU  - Irwin Nazareth
AU  - John R Hurst
AU  - Peter M A Calverley
AU  - Michael J Sweeting
AU  - Jadwiga A Wedzicha
TI  - Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial
AID  - 10.1136/thoraxjnl-2015-207194
DP  - 2015 Oct 01
TA  - Thorax
PG  - 930--938
VI  - 70
IP  - 10
4099  - http://thorax.bmj.com/content/70/10/930.short
4100  - http://thorax.bmj.com/content/70/10/930.full
SO  - Thorax2015 Oct 01; 70
AB  - 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).