Daptomycin eluted from calcium sulfate appears effective against Staphylococcus.

The emergence of resistant strains of Gram-positive organisms in osteomyelitis creates treatment challenges. Daptomycin is an antibiotic that shows promise for treating some resistant strains of Gram-positive infections; however, it has not been widely used clinically for the treatment of osteomyelitis. We determined whether daptomycin eluted from calcium sulfate-a local delivery vehicle used for the treatment of osteomyelitis-retained activity against Gram-positive bacteria. Daptomycin was mixed with calcium sulfate hemihydrate, with both laboratory powder and a commercial kit, to form a hardened pellet. Daptomycin was eluted from calcium sulfate and retained its ability to inhibit bacterial growth of Staphylococcus aureus and Staphylococcus epidermidis for eluates gathered up to 28 days. Our preliminary data demonstrates sterilized pellets with daptomycin retained their ability to inhibit bacterial growth of certain strains of Gram-positive organisms.

Elution behavior of daptomycin-loaded calcium sulfate pellets: a preliminary study.

Daptomycin is a new antibiotic active against many resistant Gram-positive organisms and seems an appropriate candidate for local delivery for severe musculoskeletal infections. Calcium sulfate dihydrate as a delivery vehicle is readily resorbable, allows new bone formation, and can be combined with therapeutic agents. We compared the elution of daptomycin and tobramycin in calcium sulfate pellets over time and determined the dissolution rates of the pellets. Unlike other water-soluble antibiotics, daptomycin required special techniques to convert the calcium sulfate from a hemihydrate powder to a hardened dihydrate shape. The elution of daptomycin on day 1 (537 microg/mL/g) was greater than that from days 2, 3, 7, 10, 14, 21, and 28. The concentration fell to 153 microg/mL/g and 37 microg/mL/g on days 2 and 3, respectively, then remained at between 5 microg/mL/g and 7 microg/mL/g for the remainder of the study. The elution behavior of the daptomycin pellets differed from that of the tobramycin-containing pellets on days 1 through 3, but was similar from day 7 through day 28. Daptomycin-containing pellets dissolved more rapidly in vitro than tobramycin-containing pellets, although the importance of this more rapid dissolution in an in vivo situation is unknown. Using the techniques described in this paper, daptomycin can be incorporated within a calcium sulfate matrix.