ANTIBIOTIC UPTAKE BY ALVEOLAR MACROPHAGES

Abstract

Optimal therapy of infections caused by bacteria able to survive within phagocytes requires the use of antibiotics which inactivate these intracellular organisms. To define characteristics that determine entry of antimicrobial agents into phagocytes, the uptake of 14 radiolabeled antibiotics by rabbit AM [alveolar macrophages] was studied. Cell-antibiotic mixtures were incubated for 2 h and at intervals antibiotic uptake was determined by velocity-gradient centrifugation (separation of cells from extracellular antibiotic). Many drugs failed to penetrate AM readily. Cellular concentrations of penicillin G and 3 cephalosporin antibiotics were much lower than extracellular levels (C/E = < 0.1-0.4). Gentamicin, isoniazid and tetracycline attained C/E values of 0.5-0.8. The more lipid-soluble antibiotics, rifampin, lincomycin and chloramphenicol, were concentrated approximately 2-fold (C/E = 2) in AM. Ethambutol (C/E = 7) and 2 erythromycin preparations (C/E = > 20) were markedly accumulated by macrophages. In comparison with other antibiotics tested, the uptake of clindamycin was massive and rapid (C/E = 50 by 30 min). Ethambutol, erythromycin and clindamycin uptakes by AM are dependent upon oxidative metabolic processes. Detailed characterization of clindamycin uptake confirmed that the drug is accumulated by an active transport system. These findings, in association with studies of antibiotic-mediated influence on phagocytes, should provide information useful in establishing guidelines for optimal antibiotic usage.