Interaction of Intraleukocytic Bacteria and Antibiotics
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TLDR
It is suggested that a likely explanation for the survival of phagocytized bacteria in the presence of high concentrations of most antibiotics is the inability of the antibiotic to enter the phagocyte.Abstract:
Bacteria that survive inside polymorphonuclear neutrophils (PMN) following phagocytosis are protected from the bactericidal action of most antibiotics. Two possible explanations are altered metabolism by intraleukocytic bacteria or failure of antibiotics to enter the phagosome. The oxygen consumption of intraleukocytic and extraleukocytic bacteria was measured as an index of bacterial metabolism. PMN respiration and bactericidal activity were suppressed with large doses of hydrocortisone and extraleukocytic bacterial oxygen consumption was abolished by the addition of lysostaphin. Intraleukocytic bacterial continued to consume oxygen suggesting that surviving ingested micro-organisms are metabolically active. Neither penicillin (which cannot kill intraleukocytic bacteria) nor rifampin (which can kill intraleukocytic bacteria) was bactericidal for staphylococci at 5 degrees C. Thus, rifampin is not uniquely able to kill "resting" bacteria.Intraleukocytic or extraleukocytic Staphylococcus aurens were incubated with [benzyl-(14)C]penicillin for 2 h at 37 degrees C. Live intraleukocytic bacteria bound only 13% as much penicillin as live bacteria incubated with killed PMN. To measure the penetration of antibiotics into PMN, [(14)C]rifampin and [(14)C]penicillin were measured in leukocyte pellets and in the supernatant fluid. The total water space in the pellets was quantitated using tritium water and the extracellular water space was measured using Na(235)SO(4). All penicillin associated with the cell pellet could be accounted for in extracellular water. Thus penicillin was completely excluded from the leukocytes. Rifampin was concentrated in the cell pellet 2.2 times when compared with the supernatant concentration. These studies suggest that a likely explanation for the survival of phagocytized bacteria in the presence of high concentrations of most antibiotics is the inability of the antibiotic to enter the phagocyte. Rifampin, which is highly lipid soluble, can enter leukocytes and kill intracellular bacteria.read more
Citations
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References
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Rifampicin: A New Orally Active Rifamycin
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Studies on body composition iv. use of radioactive hydrogen for measurement in vivo of total body water
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Killing of Intraleukocytie Staphylococcus aureus by Rifampin: In-Vitro and In-Vivo Studies
Gerald L. Mandell,T. Keith Vest +1 more
TL;DR: The mechanism for this marked activity of rifampin in the treatment of experimental staphylococcal infections may be the unique ability of this antibiotic to kill intracellular staphyllococci.
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The effect of an NADH oxidase inhibitor (hydrocortisone) on polymorphonuclear leukocyte bactericidal activity.
TL;DR: Impaired NADH oxidase activity in normal human PMN by hydrocortisone results in reduced intracellular killing of bacteria, diminished postphagocytic oxygen consumption, decreased ability to reduce Nitro blue tetrazolium, and decreased hydrogen peroxide production.
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The Dissociation by Colchicine of Phagocytosis from Increased Oxygen Consumption in Human Leukocytes
TL;DR: Measurements of granule-associated acid phosphatase activity after phagocytosis support the morphologic observations of less degranulation in colchicine-treated leukocytes, and may be important for the anti-inflammatory effect of col chicine in acute gouty arthritis.
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