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Contrasts between phagocyte antibiotic uptake and subsequent intracellular bactericidal activity
Antimicrobial Agents and Chemotherapy
|January 1, 1986
Summary
Antibiotic entry into human polymorphonuclear lymphocytes (PMN) impacts intracellular killing of Staphylococcus aureus. Not all antibiotics that enter PMN effectively kill bacteria within these cells.
Area of Science:
- Pharmacology
- Microbiology
- Immunology
Background:
- Effective treatment of intracellular bacterial infections requires antibiotics that penetrate host cells.
- Human polymorphonuclear lymphocytes (PMN) are key immune cells involved in phagocytosing and killing bacteria.
Purpose of the Study:
- To investigate the relationship between antibiotic uptake by PMN and their intraphagocytic bactericidal activity.
- To determine which factors influence an antibiotic's effectiveness against intracellular bacteria.
Main Methods:
- Human PMN were incubated with Staphylococcus aureus.
- Antibiotic uptake by PMN and intraphagocytic bacterial survival were measured in the presence of various antibiotics.
- Antibiotics tested included clindamycin, erythromycin, rifampin, gentamicin, and penicillin G.
Main Results:
- Antibiotic entry into PMN was generally increased or unchanged after S. aureus ingestion, except for erythromycin.
- Clindamycin and erythromycin, despite high PMN levels, showed limited killing of intracellular S. aureus.
- Rifampin, gentamicin demonstrated effective intracellular killing, while penicillin G did not.
- Antibiotic uptake by PMN did not solely predict intraphagocytic antibacterial activity.
Conclusions:
- The ability of an antibiotic to enter phagocytes is insufficient to guarantee intracellular antibacterial activity.
- Factors beyond cellular penetration, such as drug concentration and intrinsic activity within the phagolysosome, are critical for effective intracellular killing.