title: Antibiotics for local delivery systems cause skeletal cell toxicity in vitro.
abstract: Antibiotic concentrations associated with antibiotic bone cements may cause skeletal cell toxicity and prevent fracture healing. We investigated toxicity effects of dose and treatment time after exposure to three antibiotics commonly used in orthopaedic local drug delivery systems. We hypothesized a threshold exists for toxicity of osteoblasts and chondrocytes after treatment with ciprofloxacin, vancomycin, or tobramycin. To test this hypothesis, we first determined whether treatment with antibiotics caused differences in cellular morphology. Cells exposed to ciprofloxacin showed considerable changes in spread, cell membrane, and extensions. We next asked what dosage of antibiotic would cause reductions in osteoblast and chondrocyte cell numbers. Ciprofloxacin at a dose greater than 100 microg/mL and vancomycin and tobramycin at doses greater than 2000 microg/mL severely decreased cellular proliferation. Finally, we questioned whether observed decreases in cell numbers were the result of increased cellular toxicity or senescence. Released lactate dehydrogenase ratios were severely increased in osteoblasts. These data suggest the balance between the targeted microbicidal effects and host cellular toxicity is critical for skeletal cell survival and function.
authors.affiliation: Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Valentin
authors.initials: V
authors.lastname: Antoci
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Adams
authors.forename: Noreen J
authors.initials: NJ
authors.lastname: Hickok
authors.forename: Irving M
authors.initials: IM
authors.lastname: Shapiro
authors.forename: Javad
authors.initials: J
authors.lastname: Parvizi
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000633:toxicity*; D001672:Biocompatible Materials; D001843:Bone Cements; D002452:Cell Count; D002462:Cell Membrane / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002939:Ciprofloxacin / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D014031:Tobramycin / Q000633:toxicity; D014640:Vancomycin / Q000633:toxicity
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D001843:Bone Cements; D002939:Ciprofloxacin; D014640:Vancomycin; D007770:L-Lactate Dehydrogenase; D014031:Tobramycin