Abstract
RATIONALE
Prophylactic antibiotic therapy prevents COPD exacerbations but concerns remain about induction of bacterial resistance.
METHOD
During a 13-week single-blind randomised placebo-controlled trial, patients with COPD and FEV1<80% received moxifloxacin 400mg/day on 5 days every 4 weeks, doxycycline 100mg/day, azithromycin 250mg 3x/week or placebo daily. Mean inhibitory concentrations(MIC) were obtained for bacterial isolates cultured from sputum pre- and post-treatment. Analysis was with linear mixed effects models and logistic regression.
RESULTS
237 isolates were detected and tested in 69 patients and dichotomised (resistant/not) where possible. Compared to placebo, post-treatment MIC was 4.79 times higher in patients who received moxifloxacin (95%CI 1.43,16.03, p=0.01), 6.23 for azithromycin (1.66,23.35, p=0.01) and 3.74 for doxycycline (1.46,9.58, p=0.01). Isolates in the doxycycline group were more likely to be resistant post-treatment than placebo (odds ratio 5.77 [1.41,23.66], p=0.01); odds ratios for moxifloxacin and azithromycin were >2 but non-significant. There was no difference in number of isolates cultured between groups post-treatment. Figure 1 shows pre/post-treatment MICs.
CONCLUSION
Each antibiotic was associated with a significant increase in the MIC of cultured isolates; odds of an isolate being clinically resistant also increased with doxycycline. The potential consequences of this observation require further investigation.
- © 2014 ERS
