EVALUATION OF LUNG-TISSUE AND HILAR LYMPH-NODE CONCENTRATIONS OF AZITHROMYCIN

Since it is believed that most infections occur in the interstitial fluid, it has been suggested to measure the concentration of antimicrobial agents in pulmonary lymph that reflects the extracellular, extra-blood-vascular milieu in the lung. The aim of this study was to investigate the lung tissue and pulmonary lymph node penetration of azithromycin after 500 mg daily oral administration for three days in patients undergoing open thoracotomy. At the end of the treatment, each subject was assigned for 5 groups of 5 patients each according to thoracotomy time after the last dose (24, 48, 96, 120 and 144 h). Azithromycin was assayed by an agar diffusion method with Sarcina lutea Z114 (DRH) used as the test organism and the Antibiotic Assay Medium 1, pH 8.5 used as the medium. All patients had a detectable concentration of azithromycin in serum 24 h after the last dose (72 h after the first dose); the concentration fell below the detection limit (0.01 mg/l(-1)) after 96 h (168 h after the first dose). Peak concentrations in lung tissue and lymph nodes were found after 48 h (96 h after the first dose). Tissue and lymph node concentrations of azithromycin were much greater than serum concentrations and these tissue and lymph node concentrations persisted after serum concentrations declined. The concentrations in lung tissue of azithromycin were always higher than corresponding concentrations in hilar lymph nodes. Our results showed that azithromycin was well distributed in interstitial fluid from which pulmonary lymph is formed and that its concentrations in lung tissue and hilar lymph nodes were over the MIC(90) values in respect of relevant respiratory pathogens even at 144 h post-treatment (192 h after the first dose).