Effect of intermittent moxifloxacin therapy on the microbiology of sputum cultures from patients with chronic obstructive pulmonary disease (the PULSE study)

Abstract number: P1789

Sethi S., Alder J.

Objectives: The PULSE study has demonstrated the efficacy and safety of intermittent pulsed therapy of moxifloxacin (MXF) (400 mg PO q.d. for 5 days every 8 weeks for 6 cycles) in the reduction in the number of exacerbations of chronic obstructive pulmonary disease (COPD). Intermittent therapy was used to reduce the potential for emergence of resistant isolates associated with chronic, daily therapy. We now present the results of sputum microbiological analysis [microbial identification, eradication, and changes in minimal inhibitory concentration (MIC)] carried out during the 72-week study in patients treated with MXF or placebo.

Methods: Sputum samples were collected from all 1149 patients in the ITT population at all clinic visits. MXF susceptibility testing was performed for Haemophilus spp., Streptococcus pneumoniae, Moraxella catarrhalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus from both treatment arms. MIC to a range of antibacterial agents was determined by broth microdilution. Frequency of isolation and changes in MIC distributions of specific pathogens were compared for the MXF and placebo arms, among patients colonised with these pathogens at randomisation.

Results: The most frequent isolates at randomisation were H. influenzae, H. parainfluenzae, S. pneumoniae, S. aureus and P. aeruginosa. MXF therapy achieved eradication in a majority of the patients colonised by H. influenzae, H. parainfluenzae, and S. pneumoniae, but not in those colonised by S. aureus or P. aeruginosa. Spontaneous eradication was seen at a significantly

lower frequency in the placebo group (Table).

MIC values to MXF remained stable for most bacterial species isolated from sputum during the study. For S. aureus and P. aeruginosa there were transient increases in MIC in some isolates during the study, but these appeared to be independent of treatment arm or timing of treatment.

Conclusion: The higher clinical efficacy of intermittent MXF therapy in the reduction of exacerbations in COPD correlates with a higher eradication of primary pathogens compared to placebo treatment. There was no consistent MXF-related increase in MIC during the 48-week PULSE study or the 24-week follow-up period. Therefore chronic intermittent therapy with MXF was effective in reducing bacterial burden without an associated increase in the emergence of resistant bacteria during the treatment period.