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Background. In Germany, rates of primary total knee arthroplasty procedures and exchange arthroplasty procedures continue to rise. Late-onset peri-prosthetic infection constitutes a serious complication whose management may be dependent upon the spectrum of micro-organisms involved. The aim of this study was to provide a retrospective analysis of the effectiveness of initial eradication measures performed as part of a two-stage procedure. Material and methods. Between 2002 and 2008, a total of 328 patients who had received a first-time diagnosis of chronic peri-prosthetic knee infection following total knee arthroplasty (TKA) subsequently underwent surgery at our clinic. The surgical approach consisted of a two-stage procedure, with the initial procedure consisting of the removal of the prosthesis and radical debridement, followed by insertion of an antibiotic-loaded static spacer. The effectiveness of the procedure was assessed after six weeks, with each patient undergoing a number of clinical and laboratory-based tests, including knee joint aspiration. Results. Staphylococcus aureus strains were responsible for 68% (n=223) of the total number of cases of periprosthetic knee infection. 19% of cases (n=62) showed evidence of gram-negative bacteria, while MRSA accounted for 15% (n=49) of cases. Six weeks after completion of the above-named treatment regimen, eradication of infection was considered successful in 289 patients (88.1%). Eradication was unsuccessful in 22% of MRSA infections (n=11) and 7% of MSSA infections (n=23). Conclusion. The treatment regimen outlined in this report is capable of achieving satisfactory results in the management of late-onset peri-prosthetic knee infection, with one exception: patients with infections caused by MRSA showed high failure rates.