Histamine Release Induced by Antimicrobial Agents and Effects of Antimicrobial Agents on Vancomycin-induced Histamine Release from Rat Peritoneal Mast Cells

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 times 10−6 ‐ 3 times 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.