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Antibiotic tolerant bacterial biofilms are notorious in causing surgical site infections (SSI). Stimulan rapid cure antibiotic-loaded calcium sulfate has shown promising results for eradication of biofilms in vitro. Antibiotic-loaded calcium sulfate beads (CSBv+t) and PMMA bone cement spacers (Spacerv+t or Spaceru), and powdered antibiotic sprinkled in the surgical site as a bolus (VP) are used to achieve high local concentrations of antibiotics. However, antibiotic concentrations in the joint using these different release methods is poorly understood. Conventional release testing relies on elution into a fixed liquid volume and is not compatible with a bolus application. Also, in periprosthetic joint infections there is liquid exchange from joint fluid and exudate. We describe an artificial draining knee model which can provide controlled drainage to better determine the predicted antibiotic concentration profile. An in vitro flow reactor model was designed which consisted of a reservoir and a pump to pump Ringers solution at flow rates taken from clinical drainage rates measured after knee revision surgery. Stimulan calcium sulfate beads were loaded with vancomycin (VAN) at 1000 mg and 240 mg tobramycin (TOB) per 10cc pack. PMMA bone cement spacers were loaded with 2g VAN and 2g TOB. These beads were added to the reactor containing 75mL Ringer's solution and the flow was initiated. In the vancomycin bolus, 1000 mg was directly added to the reactor immediately prior to initiating flow. Effluent samples were collected, and zones of inhibition (ZOI) were measured using the Kirby-Bauer method against Staphylococcus aureus UAMS-1 and Pseudomonas aeruginosa PAO1 to confirm the efficacy of antibiotic release over time. Experiments were performed in independent triplicates. The concentration of vancomycin into the reactor effluent was initially greater from the VP method as compared to the CSBv+t plus Spacerv+t method, however within 2 hours, vancomycin concentration had dropped below inhibitory levels. The CSBv+t plus Spacerv+t method provided higher concentrations of VAN and TOB than other release methods in this study suggesting a combination between VP and CSBv+t plus Spacerv+t might present an optimal combination for killing bacteria entering the surgical site and provide long term protection against subsequent biofilm formation. The in vitro elution kinetics of antibiotics is highly dependent on the specifics of the system. This continuous reactor model shows potential to more accurately predict how antibiotic released from CSB may be optimized to treat biofilms associated with SSIs.