Uptake of antibiotics by human alveolar macrophages

To provide additional criteria for therapy of pulmonary infections caused by facultative intracellular bacteria, we studied the uptake of 12 antibiotics by alveolar macrophages (AM) obtained from healthy, young volunteers by bronchoalveolar lavage. These human AM were incubated with radiolabeled antibiotics for periods as long as 2 h. Entry of antimicrobials into the cells was determined by means of a velocity-gradient centrifugation technique. Antibiotic uptake was expressed as the ratio of the cellular to the extracellular drug concentration (C/E). Penicillin G, cefamandole, and gentamicin were taken up poorly by human AM (C/E = 0.5 to 0.8). Isoniazid achieved a cellular concentration similar to the extracellular level of the drug (C/E = 0.9). Chloramphenicol, rifampin, tetracycline, and lincomycin, drugs that are lipid-soluble, were concentrated several-fold by AM (C/E = 2 to 5). The remaining antibiotics tested, clindamycin, erythromycin, erythromycin propionate, and ethambutol, were markedly concentrated by AM (C/E = 9 to 23). Accumulation of clindamycin (C/E = 23) was a rapid, active, energy-requiring process, which appeared to be dependent upon mitochondrial oxidative metabolism. The ability of the tested antimicrobial agents to enter human AM correlates well with the efficacy of these drugs in treatment of certain intracellular pulmonary infections.