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Objectives To specify the concentration of the liquid antibiotics to be added to polymethylmethacrylate (PMMA) and its impact on the quality of the spacer is the purpose of this study with liquid clindamycin added to different cements. Methods In the present study, eight different cement mixtures were prepared and investigated. In the following, number 1 indicates the references, 2 all cements after liquid clindamycin was added to the liquid cement compound, 3 all cements after liquid clindamycin was added to the cement powder, and 4 all cements after liquid clindamycin was added to the cement dough. After curing, cements were filled into metal moulds and a pressure of 3 bar was maintained for 30 min. Mechanical investigations were carried out according to ISO 5833 (2002) and DIN 53435 (2007). For microbiological tests, standardized cylindrical mouldings (diameter: 25 mm, height: 10 mm) were produced and incubated in 10 ml buffer solution at room temperature for 24 h. All eluates were generated by spreading previously established suspensions of Staphylococcus aureus, Staphylococcus epidermidis, Cutibacterium acnes and methicillin‐resistant Staphylococcus aureus (MRSA) with a 0.5 McFarland turbidity standard. Results Apparently, we found that in all investigated cases, the admixture of liquid antibiotic negatively affected the mechanical characteristics of the cement mould. Among the various test groups, the influence on the ISO compression strength and ISO flexural modulus of the investigated test groups was only minimal when liquid clindamycin was added to cement liquid. Compared to admixing of liquid clindamycin into cement powder or dough ISO compression strength and ISO flexural modulus and flexural strength showed the maximum reduction. The efficacy against chosen germs was reduced as well when liquid antibiotic was admixed instead of powder. This admixture of liquid anti‐infective agents resulted in a 234% enhanced elution after 10 days 29 a negative effect on the inhibition zones were detected during the previous period. Conclusion The admixture of powdery antibiotic is preferable to liquid antibiotics. If no powdery antibiotic is available, we can recommend the admixture of liquid antibiotic to liquid cement prior to dough production in case powdery antibiotics cannot be used. However, we discourage the admixture of liquid antibiotic to cement powder or cement dough during early low viscose phase., Experimental arrangement with Palacos R leading to the results.