Background:Several absorbable and nonabsorbable antibiotic carrier systems are available in the adjunctive surgical management of osteomyelitis of the foot, ankle, and lower leg. These carrier systems have significant limitations regarding which antibiotics can be successfully incorporated into the carrier vehicle. The calcium sulfate and hydroxyapatite Cerament Bone Void Filler is a biocompatible, absorbable ceramic bone void filler that can successfully deliver multiple heat-stable and heat-unstable antibiotics that have not been generally used before with antibiotic beads in treating musculoskeletal infections.Methods:Cerament Bone Void Filler discs with the antibiotics rifampin, vancomycin, tobramycin, cefazolin, cefepime hydrochloride, vancomycin-tobramycin, piperacillin-tazobactam, ceftazidime, and ticarcillin-clavulanate were tested in vitro against methicillin-resistant Staphylococcus aureus.Results:The zones of inhibition for the Cerament Bone Void Filler antibiotic discs plated against Staphylococcus aureusobtained were 33% to 222% greater than the minimum zones of inhibition breakpoints for bacteria susceptibility as defined by the standard set by the Clinical and Laboratory Standards Institute. Cerament Bone Void Filler discs with the antibiotics plated against Pseudomonas aeruginosaproduced zones of inhibition of 93% to 200% greater than the minimum zones of inhibition breakpoints for bacteria susceptibility as defined by the standard set by the Clinical and Laboratory Standards Institute.Conclusions:The calcium sulfate and hydroxyapatite Cerament Bone Void Filler was an excellent carrier vehicle for multiple antibiotics creating in vitro significant zones of inhibition, thus demonstrating susceptibility against Staphylococcus aureusand Pseudomonas aeruginosa,which holds tremendous promise in treating osteomyeilits. (J Am Podiatr Med Assoc 101(2): 146–152, 2011)