Interaction of mezlocillin and cefoxitin against Proteus morganii in the granuloma pouch model.

The interaction of cefoxitin and mezlocillin was studied in rats using the granuloma pouch technique. Proteus morganii strains against which cefoxitin and penicillins exhibited antagonistic antibacterial activity were selected for infection of the pouches. Animals were treated with cefoxitin and/or mezlocillin, and bacterial counts, drug levels and beta-lactamase production in the pouch exudate monitored. A significant decrease in bacterial counts was seen after administration of mezlocillin and cefoxitin in combination but not after the drugs administered alone. Drug concentrations of mezlocillin and/or cefoxitin corresponded directly to the rate of induction of beta-lactamase activity. Although both beta-lactam antibiotics induce beta-lactamase activity, administered in combination in vivo they appear to protect each other from being inactivated thus resulting in synergistic antibacterial activity.