58 The difference in exacerbation-free interval resulting from levofloxacin treatment in these two studies (300 days vs 112 days) is unclear, but may be due to the fact that 82% of patients in the latter study had selleck compound severe or very severe COPD (forced expiratory volume in 1 s [FEV1] < 50% predicted), 58 in contrast to only 27% of severe patients in the former study. 59 The pioneering trial in this field by Chodosh et al.60 demonstrated that ciprofloxacin achieved higher bacteriological eradication rates than clarithromycin, however, with a

non-significant increase in the infection-free interval associated with ciprofloxacin (142 vs 51 days, P = 0.15). The MOSAIC trial, a large study enrolling patients with stable COPD prior to an acute exacerbation, showed significant improvement in long-term outcomes with moxifloxacin during a 9-month follow-up period versus standard antibiotics (amoxicillin, clarithromycin

or cefuroxime-axetil) 55 reporting delayed onset of a composite failure event (treatment failure and/or new exacerbation and/or any further antibiotic treatment). In two other studies, gemifloxacin was associated with significantly lower relapse rates in 6 months, non-significant reduction in hospitalisations (P = 0.059) and better health status scores at 6 months than clarithromycin. 9 and 31 A smaller study, conducted by Nouira et al., was not able Cediranib (AZD2171) to show any difference in long-term outcomes in hospitalised

patients A-1210477 nmr between ciprofloxacin and trimethoprim-sulfamethoxazole. 61 In the recently published MAESTRAL study, while moxifloxacin treatment was comparable to amoxicillin/clavulanic acid for the primary endpoint of clinical failure at 8-weeks post-therapy, moxifloxacin resulted in significantly lower clinical failure and higher bacteriological eradication in a sub-population of patients with bacterial pathogens isolated from sputum at the time of exacerbation. 28 The exact mechanism(s) underlying the effects of acute antibiotic treatment on long-term outcome is (are) uncertain, though eradication of the infecting bacteria causing the exacerbation is likely to play a key role. This was best demonstrated in the MAESTRAL study, in which in the post-hoc assessment of a sub-group of patients with bacterial pathogens isolated from sputum at the time of exacerbation, a significant relationship was observed between bacterial eradication at end-of-treatment (EOT) and the rate of clinical cure at 8 weeks. This relationship was seen both in the overall population and in moxifloxacin-treated patients, though the correlation was not present in those treated with amoxicillin/clavulanic acid.