The selection in vitro of antibiotics with activity against intracellular S. aureus

The activity of a range of antibiotics on intracellular Staphylococcus aureus was examined using an in vitro system in which staphylococci survived within bovine neutrophils and extracellular organisms were killed by lysostaphin. Cloxacillin in the presence of lysostaphin caused a reduction in the number of viable intracellular S. aureus but cloxacillin alone failed to reduce such bacteria significantly. The cloxacillin appeared to sensitize the staphylococci to lysis by extracellular traces of lysostaphin following neutrophil disruption. Extracellular staphylococci which remained viable after exposure to cloxacillin in the absence of lysostaphin were subsequently killed more rapidly by neutrophils, but this was not found with bacteria exposed to cloxacillin while inside cells. Vancomycin with lysostaphin produced a similar but smaller sensitization effect but this antibiotic also appeared to increase survival of intracellular staphylococci when compared with controls, possibly by impeding neutrophil bactericidal mechanisms. The only other antibiotic to show significant intracellular killing was rifampicin, and in this case the action was independent of lysostaphin.