Uptake of antimicrobial agents by human polymorphonuclear leucocytes

Abstract

The uptake of the antimicrobial agents tinidazole, josamycin and penicillin G by normal human polymorphonuclear leucocytes (PMNs) was measured in vitro, using radiolabeled drugs. Extracellular concentrations corresponding to therapeutically effective serum levels of the drugs were used. Penicillin G penetrated the leucocyte membrane poorly, the ratio of the cell-associated to the extracellular concentration (C/E) being between 0.23 and 0.54. In contrast, tinidazole and josamycin were accumulated by the cells: C/E for tinidazole varied from 1.38 to 1.56 and C/E for josamycin from 3.5 to 21.4, depending on incubation times. It is inferred that these two compounds are capable of inactivating intracellular organisms and would therefore be useful for treating or preventing chronic infections caused by pathogens which survive intracellularly. The extraordinarily high accumulation of josamycin by PMNs could not easily be reversed by repeated cell washing and might be explained by the existence of an active transport mechanism.