Contrasts between phagocyte antibiotic uptake and subsequent intracellular bactericidal activity

Abstract

An ideal antibiotic for therapy of infections due to facultative intracellular organisms would enter phagocytes readily and kill intracellular bacteria. We have examined the consequences of antibiotic uptake by human polymorphonuclear lymphocytes (PMN) on intraphagocytic bactericidal activity, using antibiotics which differ markedly in their ability to enter PMN. After ingestion of Staphylococcus aureus, PMN were evaluated in regard to uptake of antibiotics and survival of intraphagocytic bacteria in the presence or absence of these drugs. Except for erythromycin, the uptake of which was slightly decreased, the entry of tested antibiotics into PMN was increased or unchanged after ingestion of S. aureus. Clindamycin and erythromycin, which achieved high cellular levels in PMN, failed to produce a significant reduction in viable intraphagocytic S. aureus during 3 h of antibiotic exposure. In contrast, rifampin, which was concentrated severalfold by phagocytes, was able to kill intracellular staphylococci. Gentamicin and penicillin G penetrated PMN rather poorly. However, while gentamicin demonstrated efficient intraphagocytic killing of bacteria, penicillin had no intracellular effect during the 3-h incubation period. These observations document that the ability to enter phagocytes is only one of the factors which determine the intracellular antibacterial activity of an antibiotic.