Implant-associated infections are often resistant to antibiotic therapy. Routine sensitivity tests fail to predict therapeutic success. Therefore experimental in vitro tests were sought that would better correlate with drug efficacy in device-related infections. The activity of six different antibiotics against methicillin-resistant Staphylococcus epidermidis was investigated. In vivo studies were performed with the guinea pig tissue-cage animal model; in vitro studies with minimum inhibiting and bactericidal concentrations, time-kill studies of growing and stationary-phase microorganisms, the killing of glass-adherent S. epidermidis. Drug efficacy on stationary and adherent microorganisms, but not minimum inhibiting concentrations, predicted the outcome of device-related infections. Rifampin cured 12 of 12 infections and was also the most efficient drug in any experimental in vitro test. Similarly, the failure of ciproftoxacin to eradicate foreign body infections correlated with its low efficacy on stationary-phase and adherent S. epidermidi