Infection following total joint replacement remains a problem that has not been solved so far. The treatment options include removal of the implant and a delayed reconstruction or a direct exchange operation. Among patients with stable implants and short duration of infection as well as in patients who for certain reasons are inoperable, antibiotic therapy with a combination of rifampicin-ciprofloxacin may be a reasonable treatment option for curing staphyloccocal infection without removal of the implant. A case study of a Staphylococcus epidermidis (coagulase-negative) infection following delayed revision total knee replacement after septic loosening of a knee arthroplasty and its successful conservative treatment with rifampicin-ciprofloxacin is described. Alternative rifampicin combinations are discussed with respect to recently developed pharmacodynamical and pharmacokinetical findings of biofilm active drugs.