Azithromycin concentrations at the sites of pulmonary infection

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Abstract
Azithromycin is a new macrolide antimicrobial. The distribution to the potential sites of pulmonary infection was assessed after the administration of a single 500 mg oral dose to 22 patients undergoing fibreoptic bronchoscopy. Concentrations of azithromycin in sputum, bronchial mucosa, eptihelial lining fluid (ELF) and alveolar macrophages (AM) were determined at intervals up to 96 h after dosing. The mean serum concentration was low at 12 h (0.13 micrograms.ml-1, SEM 0.05) but was still detectable at 96 h (0.01 micrograms.ml-1). In contrast, peak sputum ELF, bronchial mucosal and AM levels were found at 48 h. Bronchial mucosal concentrations were significantly greater than ELF concentrations, which were in turn greater than sputum concentrations. Mean peak AM concentrations were sixfold greater than bronchial mucosal concentrations (23 micrograms.ml-1, SEM 5.1 and 3.89 micrograms.ml-1, SEM 1.2, respectively). The high intracellular concentrations indicate that azithromycin is likely to be effective for sensitive intracellular pathogens and the favourable penetration into sputum, ELF and bronchial mucosa suggest that it should be useful in pneumonia and bronchial infections.