A model to show the role of extracellular beta-lactamases in mediating staphylococcal resistance.

Considerable amounts of extracellular beta-lactamase are liberated from penicillin-resistant staphylococci into the surrounding medium. The accumulation of exoenzyme in conventional in-vitro test systems may result in rapid inactivation of hydrolysable antibiotics, while in vivo the concentration of extracellular beta-lactamase varies depending on the site of infection. Using a new open test model designed to eliminate the effect of exoenzyme, it could be shown that resistance of beta-lactamase-producing staphylococci to mezlocillin as seen in the broth dilution test was mediated predominantly by the extracellular beta-lactamase fraction. Animal experiments suggested that mezlocillin may exhibit a therapeutic effect against beta-lactamase-producing staphylococci under certain conditions in vivo which prevent build-up of exoenzyme.