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Effects of aminoglycoside antibiotics on polymorphonuclear leukocyte function in vivo
Abstract:
In vitro incubation of aminoglycoside antibiotics with human polymorphonuclear leukocytes (PMNs) has been shown to induce abnormalities in cell function. This study was designed to determine whether there are similar abnormalities in leukocyte function after exposure to the action of these agents in vivo. Four aminoglycosides (gentamicin, tobramycin, netilmicin, and amikacin) were tested. In vitro incubation did not induce a chemotactic defect when measured by an under-agarose method. However, inhibition of candidacidal activity was reproducible after in vitro incubation of all aminoglycosides tested. Nevertheless, when the aminoglycosides were administered intravenously to normal volunteers, PMN function, including adherence to nylon wool columns, chemotaxis, phagocytosis, and killing of Candida albicans, was unimpaired at 1, 3, and 24 h postinfusion. Therefore, we conclude that aminoglycoside antibiotic administration does not induce PMN dysfunction in vivo.
Insights
Aminoglycoside antibiotics did not impair polymorphonuclear leukocyte (PMN) function in vivo, despite in vitro studies showing reduced candidacidal activity. This suggests clinical use of these antibiotics does not cause immune cell dysfunction.
Area of Science:
- Pharmacology
- Immunology
- Microbiology
Background:
- Aminoglycoside antibiotics are known to affect human polymorphonuclear leukocyte (PMN) function in vitro.
- Previous studies indicate potential for impaired cell function upon exposure to these agents.
Purpose of the Study:
- To investigate whether in vivo administration of aminoglycoside antibiotics causes abnormalities in human PMN function.
- To compare in vitro and in vivo effects of four specific aminoglycosides: gentamicin, tobramycin, netilmicin, and amikacin.
Main Methods:
- In vitro incubation of PMNs with aminoglycosides to assess chemotaxis and candidacidal activity.
- Intravenous administration of aminoglycosides to normal volunteers.
- Assessment of PMN function (adherence, chemotaxis, phagocytosis, candidacidal activity) at 1, 3, and 24 hours post-infusion.
Main Results:
- In vitro incubation demonstrated inhibition of candidacidal activity by all tested aminoglycosides.
- In vitro incubation did not induce a chemotactic defect using the under-agarose method.
- In vivo administration of aminoglycosides did not impair PMN adherence, chemotaxis, phagocytosis, or candidacidal activity.
Conclusions:
- Aminoglycoside antibiotics do not induce polymorphonuclear leukocyte (PMN) dysfunction in vivo.
- Clinical administration of these antibiotics appears safe concerning PMN immune function.
- Discrepancies between in vitro and in vivo findings highlight the importance of in vivo validation.