Cellular uptake and intracellular activity of antibiotics against Haemophilus influenzae type b.

The ability of penicillins and chloramphenicol to enter human polymorphonuclear leukocytes (PMNLs) and their antibacterial activity against intracellular Haemophilus influenzae type b were studied. Penicillin was excluded whereas chloramphenicol was concentrated in PMNLs; chloramphenicol uptake was not dependent on PMNL energy and was not competitively inhibited by unlabeled drug. PMNLs that had phagocytized opsonized H. influenzae type b were examined after incubation for 24 hr. In the absences of antibiotics, intact intracellular H. influenzae type b organisms were observed in PMNLs by electron microscopy. These PMNLs contained 10(4.5) colony-forming units (cfu) of H. influenzae type b. Addition of penicillin or ampicillin at four, 20, or 40 times the minimal bactericidal concentration (MBC) decreased this density from 10(4.5) to 10(3.5) cfu. In contrast, addition of chloramphenicol at four times the MBC reduced the density to approximately 100 cfu; at 10 times the MBC it reduced the density to approximately 10 cfu. Thus, lipid-soluble antibiotics such as chloramphenicol are concentrated and are bioactive within PMNLs. Such antibiotics may have a significant advantage at the cellular level.