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Histamine release induced by antimicrobial agents and effects of antimicrobial agents on vancomycin-induced histamine
T Toyoguchi1, M Ebihara, F Ojima
1Department of Pharmacy, Yamagata University Hospital, Japan.
Abstract:
Vancomycin and certain fungicides may cause anaphylactoid reactions. We investigated the effects of vancomycin, miconazole and fluconazole on histamine release in rat peritoneal mast cells. Vancomycin and miconazole provoked histamine release in a dose-dependent manner. In contrast, fluconazole did not provoke histamine release at concentrations of 3 x 10(-6)-3 x 10(-3) M. Vancomycin is efficacious in the treatment of gram-positive bacterial infections; patients presenting themselves with mixed infections require concomitant therapy with a second antimicrobial agent. We investigated the effect of fosfomycin sodium, cilastatin sodium or fluconazole on vancomycin-induced histamine release. Fosfomycin sodium inhibited vancomycin-induced histamine release but neither cilastatin sodium nor fluconazole inhibited it in the mole ratios of daily doses used in humans. These results suggest that vancomycin and miconazole provoke histamine release in rat mast cells, but that fluconazole probably does not, while fosfomycin sodium may inhibit vancomycin-induced histamine release.
Insights
Vancomycin and miconazole trigger histamine release in rat mast cells, but fluconazole does not. Fosfomycin sodium may inhibit vancomycin-induced reactions, suggesting potential therapeutic benefits.
Area of Science:
- Pharmacology
- Immunology
- Toxicology
Background:
- Anaphylactoid reactions can be associated with vancomycin and certain antifungal agents.
- Understanding drug-induced histamine release is crucial for patient safety.
Purpose of the Study:
- To investigate the effects of vancomycin, miconazole, and fluconazole on histamine release from rat peritoneal mast cells.
- To determine if fosfomycin sodium, cilastatin sodium, or fluconazole can inhibit vancomycin-induced histamine release.
Main Methods:
- Rat peritoneal mast cells were used to assess histamine release.
- Dose-dependent effects of vancomycin, miconazole, and fluconazole were evaluated.
- Inhibition of vancomycin-induced histamine release by other agents was tested at human-equivalent doses.
Main Results:
- Vancomycin and miconazole induced dose-dependent histamine release.
- Fluconazole did not provoke histamine release within the tested concentration range.
- Fosfomycin sodium inhibited vancomycin-induced histamine release, while cilastatin sodium and fluconazole did not.
Conclusions:
- Vancomycin and miconazole are implicated in histamine release from rat mast cells.
- Fluconazole appears unlikely to cause histamine release.
- Fosfomycin sodium demonstrates potential to mitigate vancomycin-induced histamine release.