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Cellular Uptake and Intracellular Activity of Antibiotics against Haemophilus influenzae Type B

Richards F. Jacobs, Christopher B. Wilson, Judy G. Laxton, Joel E. Haas and Arnold L. Smith
The Journal of Infectious Diseases
Vol. 145, No. 2 (Feb., 1982), pp. 152-159
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30082273
Page Count: 8
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Cellular Uptake and Intracellular Activity of Antibiotics against Haemophilus influenzae Type B
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Abstract

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 absence 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, 10, 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 ∼ 100 cfu; at 10 times the MBC it reduced the density to ∼ 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.

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