Long-term antibiotics unhelpful in stable COPD

Thursday, 23 Jul 2015

Three months of antibiotic treatment is no better than placebo in reducing the airway bacterial load in patients with stable COPD, a new study has shown.

There was also no difference in total bacterial load assessed by quantitative PCR rather than culture, or in sputum inflammatory markers, but treatment markedly increased antibiotic resistance.

The findings support current Australian COPD-X guidelines stating that current evidence does not support routine long-term antibiotic use to prevent COPD exacerbations.

Dr Simon Brill and colleagues at the UK National Heart and Lung Institute randomised 99 patients to treatment with moxifloxacin, doxycycline or azithromycin or placebo.

Their FEV1 averaged 44-53 % predicted in the four groups, their mean age was 68-71 years, and smoking history averaged about 55 pack-years.

The study was prompted by earlier research showing that exacerbation frequency is linked to airway bacterial colonisation of clinically stable patients, and suggestions that long-term antibiotics could improve the situation.

“The best evidence for this comes from the macrolide antibiotics, with both erythromycin and azithromycin shown to significantly reduce exacerbation frequency although at the expense of auditory decrements and a possible increase in cardiovascular risk,” Dr Brill wrote in Thorax.

“ There is less evidence for other antibiotic classes in stable COPD, although the fluoroquinolone moxifloxacin has shown some efficacy when used in a pulsed dosing regimen, and with no comparative studies there are few data to inform the optimum antibiotic choice.

“There are also growing concerns regarding the development of antibiotic resistance in airway bacteria.”

Patients took 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.

Pulsed moxifloxacin had the biggest numerical effect on cultured bacterial numbers, although it was not significantly different from the placebo group, and also caused the highest incidence of adverse events.

Australian COPD-X guidelines acknowledge that trials of long-term low-dose oral macrolides reduce exacerbations in patients with moderate to severe COPD and a past history of recurrent exacerbations, according to COPD-X.

Although a key study by Albert et al demonstrated benefit from azithromycin, it is not PBS-listed for long-term therapy, can be associated with hearing loss and increases macrolide resistance.

“Prudence would suggest that this treatment should be reserved for patients who have severe disease with recurrent exacerbations in whom other treatments have been optimised,” the guidelines state.

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