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Antibiotic entry into human polymorphonuclear leukocytes

R C Prokesch, W L Hand

    Antimicrobial Agents and Chemotherapy
    |March 1, 1982
    PubMed
    Summary
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    Certain antibiotics effectively penetrate human phagocytes, crucial for treating intracellular bacterial infections. Clindamycin and erythromycin show high uptake via active transport, indicating potential for enhanced intracellular pathogen therapy.

    Area of Science:

    • Pharmacology
    • Microbiology
    • Cell Biology

    Background:

    • Intracellular bacteria pose treatment challenges as they survive within host phagocytes.
    • Effective antimicrobial agents are needed to target these intracellular pathogens.

    Purpose of the Study:

    • To investigate factors influencing antimicrobial agent entry into human phagocytes.
    • To quantify the uptake of various antibiotics by polymorphonuclear leukocytes (PMN).

    Main Methods:

    • Studied the uptake of 13 radiolabeled antibiotics by human peripheral blood PMN.
    • Used velocity gradient centrifugation to differentiate cell-associated from extracellular antibiotics.
    • Measured antibiotic concentrations over a 2-hour incubation period.

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    Main Results:

    • Penicillin G and cephalosporins showed poor PMN penetration (C/E < 0.5).
    • Gentamicin and isoniazid had C/E ratios near 1.0.
    • Chloramphenicol, rifampin, and lincomycin were concentrated twofold (C/E = 2).
    • Ethambutol (C/E = 5), clindamycin (C/E = 11), and erythromycin (C/E = 10-13) were markedly concentrated.
    • Clindamycin uptake was rapid and energy-dependent, mediated by a saturable active transport system (Km = 2 mM, Vmax = 5 nmol/45 s/10^6 cells).

    Conclusions:

    • Antibiotic uptake by PMN varies significantly, with lipid solubility and active transport playing key roles.
    • Clindamycin and erythromycin demonstrate substantial intracellular accumulation.
    • Understanding these uptake mechanisms can guide the development of more effective therapies for intracellular bacterial infections.