In vitro studies simultaneously examining effect of oxacillin on uptake of radiolabeled streptomycin and on associated bacterial lethality in Staphylococcus aureus.

We studied the effects of various concentrations of oxacillin on streptomycin uptake and killing for several strains of Staphylococcus aureus. When streptomycin was present in concentrations below the MIC, addition of oxacillin at concentrations greater than or equal to the MIC was associated with both significantly increased aminoglycoside uptake and killing. In contrast, when streptomycin was present in concentrations above the MIC, no increase of streptomycin uptake was noted with the addition of oxacillin, and killing was no greater than what would have been expected with a simply additive effect. Similar studies in a strain of S. aureus selected for high-level streptomycin resistance also demonstrated increased streptomycin uptake in the presence of concentrations of oxacillin above the MIC; however, killing was no greater than that seen with oxacillin alone. These studies provide data which are potentially important in designing a rational approach to clinical use of combination antibiotic therapy.