ru-66647 and Pulmonary-Disease--Chronic-Obstructive

Systemic antibiotic treatment is established for many pulmonary diseases, e.g., cystic fibrosis (CF), bronchiectasis and chronic obstructive pulmonary disease (COPD) where recurrent bacterial infections cause a progressive decline in lung function. In the last decades inhalative administration of antibiotics was introduced into clinical routine, especially tobramycin, colistin, and aztreonam for treatment of CF and bronchiectasis. Even though they are important in systemic treatment of these diseases due to their antimicrobial spectrum and anti-inflammatory and immunomodulatory properties, macrolides (e.g., azithromycin, clarithromycin, erythromycin, and telithromycin) up to now are not administered by inhalation. The number of in vitro aerosol studies and in vivo inhalation studies is also sparse. We analyzed publications on preparation and administration of macrolide aerosols available in PUBMED focusing on recent publications. Studies with solutions and dry powder aerosols were published. Publications investigating physicochemical properties of aerosols demonstrated that macrolide aerosols may serve for inhalation and will achieve sufficient lung deposition and that the bitter taste can be masked. In vivo studies in rats demonstrated high concentrations and areas under the curve sufficient for antimicrobial treatment in alveolar macrophages and epithelial lining fluid without lung toxicity. The obtained data demonstrate the feasibility of macrolide inhalation which should be further investigated.

Topics: Administration, Inhalation; Aerosols; Animals; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Clarithromycin; Cystic Fibrosis; Erythromycin; Humans; Ketolides; Lung; Macrolides; Pulmonary Disease, Chronic Obstructive; Rats

The aim of this study was to evaluate the clinical efficacy of telithromycin administered for 5 days at a dosage of 800 mg/day, in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) presenting with at least 2 of Anthonisen's criteria including the increase of purulence.. During this multicenter (211 private lung specialists), prospective, non-comparative, open-labeled French study, 365 patients were included between April 2002 and March 2003. Clinical efficacy was assessed on D12-D19 by the rate of clinical success as defined by recovery or clinical improvement (main endpoint) according to the number of exacerbation episodes during the previous year.. On D12-D19 clinical success rate in the per protocol global population was 88.0% and respectively 87.9% in patients with or=4 episodes in the previous year. These success rates were similar to those in the intent-to-treat population. Safety, assessed on 359 patients, was satisfactory, with mainly digestive disorders related to the treatment in 3.9% of the patients. No treatment-related serious adverse events were observed.. This study, conducted among private practitioners in France according to COPD classification as defined by official recommendations, validates the results obtained in previous studies. Our results confirm the place attributed to telithromycin in the treatment of patients presenting with AECOPD without chronic respiratory failure, according to ongoing official recommendations.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Female; France; Humans; Ketolides; Male; Middle Aged; Patient Selection; Private Practice; Pulmonary Disease, Chronic Obstructive; Risk Factors; Treatment Outcome