title: Calcium hydroxide ameliorates tobramycin toxicity in cultured chick tibiae.
abstract: Results from this laboratory have shown that bone metabolism is directly related to extracellular pH and that high concentrations of tobramycin released from impregnated polymethylmethacryrate (PMMA) beads has pH-dependent toxic effects on bone. In the present study, beneficial effects of calcium hydroxide-impregnated PMMA were investigated regarding tobramycin toxicity and bone metabolism in chick embryo tibiae in vitro. Also using Ca(OH)2 as a pH regulator, the antibiotic efficacy of tobramycin-impregnated PMMA was evaluated with respect to inhibition of Staphylococcus aureus growth. When Ca(OH)2 was added to PMMA beads containing tobramycin, the beads released hydroxyl and calcium ions into the culture medium and released more antibiotic than beads containing only tobramycin. Bone metabolism (glycolysis, total protein synthesis, and collagen synthesis) was enhanced by Ca(OH)2-impregnated beads with or without tobramycin. Additionally, bacterial growth was inhibited more strongly when S. aureus was incubated with tobramycin- and Ca(OH)2-impregnated PMMA disks than with disks containing only tobramycin. This study demonstrates the feasibility of adding Ca(OH)2 to tobramycin-impregnated PMMA beads as a regulator of local pH and a promoter of bone metabolism for protection of bone when high concentrations of tobramycin are used to treat osteomyelitis. It also suggests that lower concentrations of antibiotic may be effective if Ca(OH)2 and tobramycin are administered simultaneously.
authors.affiliation: Baxter Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, NC 28232-2861, USA.
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: H
authors.initials: H
authors.lastname: Murakami
authors.forename: W K
authors.initials: WK
authors.lastname: Ramp
authors.forename: M C
authors.initials: MC
authors.lastname: Hudson
authors.forename: M T
authors.initials: MT
authors.lastname: Nousiainen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D002126:Calcium Hydroxide / Q000494:pharmacology*; D002642:Chick Embryo; D003470:Culture Media; D004337:Drug Carriers; D006863:Hydrogen-Ion Concentration; D009924:Organ Culture Techniques; D010019:Osteomyelitis / Q000188:drug therapy; D019904:Polymethyl Methacrylate; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013977:Tibia / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D014031:Tobramycin / Q000037:antagonists & inhibitors / Q000633:toxicity*
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D004337:Drug Carriers; D019904:Polymethyl Methacrylate; D002126:Calcium Hydroxide; D002118:Calcium; D014031:Tobramycin