What are the most appropriate antibiotics for the treatment of acute exacerbation of chronic obstructive pulmonary disease? A therapeutic outcomes model

Abstract

To predict the clinical efficacy of several antimicrobials in the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A probability model (therapeutic outcomes model) was used to predict the likelihood of clinical success with particular antimicrobial agents in the treatment of patients with AECOPD, both in those clinically diagnosed (total patients with an AECOPD diagnosis regardless of the cause) and in those with bacterial AECOPD. The model took into account the following variables: (i) the proportion of patients with a clinical diagnosis of AECOPD and non-bacterial disease; (ii) likelihood of spontaneous resolution of a non-bacterial infection; (iii) prevalence of subcauses (different bacterial species) in bacterial AECOPD; (iv) rates of spontaneous resolution of bacterial AECOPD; and (v) antimicrobial efficacy of each antibiotic against each bacterial species (susceptibility based on PK/PD breakpoints). Fluoroquinolones (levofloxacin, ciprofloxacin and moxifloxacin), a new third-generation oral cephalosporin (cefditoren) and high doses of amoxicillin/clavulanate were the antimicrobials with the highest predicted clinical efficacy both in mild-moderate AECOPD and in severe AECOPD (rates of 89.2% to 90.5% and 80.3% to 88.1%, respectively), whereas cefaclor, azithromycin, erythromycin and clarithromycin had the lowest predicted clinical efficacy (rates of 79.1% to 81.3% and 51.8% to 55.6% for mild-moderate and severe AECOPD, respectively), which was not much higher than that predicted for placebo (73.6% and 45.5%, respectively). According to our model, fluoroquinolones (levofloxacin, ciprofloxacin and moxifloxacin), cefditoren and amoxicillin/clavulanate are the most appropriate antibiotics for the treatment of patients with AECOPD in terms of predicted clinical efficacy, with wide differences with respect to other antibiotics commonly used in the treatment of these patients, such as clarithromycin and azithromycin.