Effect of antibiotic protein binding on the killing rate of Staphylococcus aureus and on the paradoxical phenomenon

The killing kinetics of Staphylococcus aureus, exposed to various concentrations of dicloxacillin in broth and in broth with 40 g/l human albumin was studied. When the free concentrations of dicloxacillin were identical in the two media, no difference in killing capacity could be demonstrated at concentrations above MIC, indicating that only the free antibiotic fraction is antibacterially active. However, at concentrations identical to the MIC, a better bactericidal effect in the medium containing albumin was found. In experiments where equal total concentrations were compared in the two media, an increasing bactericidal effect in the medium containing albumin could be demonstrated at concentrations between 10-100 X MIC. The most probable explanation for this was a prominent paradoxical effect with increasing antibiotic concentrations on the killing rate of S. aureus in broth. This effect was neutralized in the presence of albumin due to the lower free antibiotic concentration in this medium.