Daptomycin: local application in implant-associated infection and complicated osteomyelitis.

BACKGROUND: The rise of highly resistant bacteria creates a persistent urge to develop new antimicrobial agents. This paper investigates the application of the lipopeptide antibiotic daptomycin in infections involving the human bone. METHODS: Compressive and tensile strength testing of daptomycin-laden PMMA was performed referring to the ISO 5833. The microstructure of the antibiotic-laden PMMA was evaluated by scanning electron microscopy. Intracellular activity of daptomycin was determined by a human osteoblast infection model. Elution kinetics of the antibiotic-laden bone cement was measured by using a continuous flow chamber setup. RESULTS: There was no significant negative effect of adding 1.225% and 7.5% per weight of daptomycin to the PMMA. There was no significant difference in intracellular activity comparing gentamicin to daptomycin. Elution of daptomycin from PMMA showed within the first-hour initial peak values of 15-20 µg/mL. CONCLUSION: Daptomycin has a certain degree of activity in the intracellular environment of osteoblasts. Daptomycin admixed to PMMA remains bactericidal and does not significantly impair structural characteristics of the PMMA. The results of this paper suggest that daptomycin might be a potent alternative for treating osteomyelitis and implant-associated infection in trauma and orthopedic surgery caused by multiresistant strains.

Influence of synovial fluid on human osteoblasts: an in vitro study.

Osseous graft healing at the tendon bone interface after anterior cruciate ligament (ACL) reconstruction is unsatisfactory in 10-25%, depending on the evaluation criteria or the kind of graft used for reconstruction. Mechanical as well as biological aspects are currently discussed. Since osteoblasts play an important role in the osseous integration of an ACL graft, we hypothesize that synovial fluid (SF), when entering the bone tunnel, has an inhibitory effect on osteoblasts. In order to verify this hypothesis, human osteoblasts (p3) were incubated in the presence of SF or partially purified SF. Proliferation was assayed using MTT or BrdU assay. Gene expression of osteoblast markers (alkaline phosphatase, collagen I, and osteocalcin) were determined by TaqMan analysis. In the control group, SF was exchanged by fetal calf serum (FCS). The results showed osteoblast proliferation in the presence of SF as well as in partially purified heat-pretreated synovial fluid. Native SF induced alkaline phosphatase and collagen I gene expression. No induction of the osteocalcin gene was observed in the experiment. These results were comparable to that obtained with FCS. These findings suggest that SF stimulated proliferation of osteoblasts in vitro. This effect is mediated, in part, by heat-stable components of SF. In addition, the expression of osteoblast marker genes alkaline phosphatase and collagen I, but not osteocalcin, was induced by SF. Therefore, problems associated with cruciate ligament reconstruction might be due to the inhibition of osteoblast differentiation. If so, this is not a specific attribute of SF, but also applies to serum.