ru-66647 and Bronchiectasis

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

This report presents the case of a patient associated with a Streptococcus pneumoniae isolate that was resistant to a new ketolide antibiotic, telithromycin (minimum inhibitory concentration: 4 microg/ml). The patient, a 61-year-old female with bronchiectasis, was treated with 200-400 mg of clarithromycin daily for 6 years until the isolation of the resistant strain but without prior exposure to telithromycin. The strain was isolated from her sputum but not from the nasopharynx. This isolate carried erm(B) and had mutations in 23S rRNA and riboprotein L4. To our knowledge, this is the first case report concerning a telithromycin-resistant S. pneumoniae isolate in Japan by mutation in L4. Although the long-term clarithromycin administration may have contributed to the induction of resistance in this patient, this could not be confirmed, since S. pneumoniae was not isolated until the present episode.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bronchiectasis; Drug Resistance, Bacterial; Female; Humans; Japan; Ketolides; Methyltransferases; Middle Aged; Mutation; Ribosomal Proteins; RNA, Ribosomal, 23S; Streptococcus pneumoniae