The development and implementation of a bone cement-based spacer with a long-lasting antimicrobial effect remains an urgent problem when performing an operation on two-stage prosthetics of large joints. Extracts from samples of bone cement compositions with gentamicin, vancomycin, Poviargol (nanoclusters of silver) and high molecular weight polyvinylpyrrolidone (PVP) were tested for cytotoxicity in a culture of human embryo skin fibroblast cells and antimicrobial effect (disk diffusion and quantitative suspension methods) against Staphylococcus epidermidis ATCC 14990 (sensitive to gentamicin) and clinical isolate S. epidermidis 5027207 (resistant to gentamycin, MIC 310 μg/ml). Extracts with gentamicin, vancomycin and 3% and 5% poviargol had a cytotoxic effect on fibroblasts in contrast to extracts containing poviargol and PVP. With respect to the sensitive strain of Staphylococcus, the antimicrobial effect of the control extract with gentamicin remained at the level of the requirements of EUCAST-2018 in the level of sensitivity of S. epidermidis to gentamicin (delayed zone > 18 mm) for up to 2 months. Samples with 1% poviargol and 1% or 8% PVP had an antimicrobial effect in the period up to 292 days, when the growth zones of the test strain were 11,3±0,7 mm and 12,3±0,3 mm, respectively. In relation to the resistant clinical isolate S. epidermidis 5027207, the extract from bone cement with gentamicin is not effective. When vancomycin was added, the antimicrobial effect was observed up to 15 days. Extracts with poviargol and PVP had a prolonged antimicrobial effect during 292 days of observation. When evaluating the effectiveness of an antimicrobial composition containing antiseptics, the requirements of EUCAST-2018 are not applicable. We believe that the presence of any zone of growth inhibition of an antibiotic-resistant microorganism indicates the manifestation of the antimicrobial activity of the composition against it. The quantitative suspension test showed a decrease in the level of the microbial population of both sensitive and resistant Staphylococcus by 3 log10 in extracts with poviargol and PVP on day 292. The prospect of using silver-containing antiseptic and high-molecular polyvinylpyrrolidone as a component of detoxification and prolongation of the antimicrobial effect of the composition based on bone cement was evaluated.