Fabrication of antibiotic-loaded dissolvable calcium sulfate beads: an in vitro mixing lab utilizing various antibiotic mixing formulas

Abstract

Chronic periprosthetic joint infection (PJI) is a devastating complication that requires an aggressive eradication protocol. Local antimicrobial delivery via dissolvable calcium sulfate (CaSO ${}_4$ ) using small-sized beads (3-8 mm) has been utilized as an adjunctive treatment combined with implant exchange, radical debridement, and antimicrobial loaded acrylic spacers. The non-exothermic setting of CaSO ${}_4$ theoretically allows for any antimicrobial agent to be used, so long as mixing methods provide a consistent fabrication within a reasonable set time. This study performed the first in vitro mixing study, in which various antimicrobial agents, used singularly and in combination, were mixed with a synthetic CaSO ${}_4$ product to observe and document their interactions. The study was performed in a simulated operating room environment. We report a standard mix formula with set times, testing 22 different antimicrobial agents, combinations, and doses. For some antimicrobials and combinations, set times using the standard formula were either too fast or exceedingly slow. For these 14 antimicrobial agents and combinations, we were able to arrive at individualized mixing methods. We present all mixing formulas and set times. In all, we were able to establish mixing methods that incorporate all antimicrobial agents and combinations that we have seen utilized via surgeon-directed use.

Figure 1

Photograph of 4.8 mm bead mat. The antimicrobial-loaded CaSO ${}_{\mathrm{4}}$ paste is shown after spreading the paste into the molds. Once applied, the bead mats were left on the countertop to set, in order to imitate operating room procedure. Time measurements were recorded to establish a set time for each formulation.