Interaction of tobramycin and pH in cultured chick tibiae.
The toxicity of tobramycin at concentrations released from antibiotic-impregnated polymethylmethacrylate beads was determined using cultured embryonic chick tibiae. Because previous results from this laboratory have shown that osteoblast metabolism is inhibited at low pH and because of the potential for a low local pH in infected bone, the antibiotic was tested in medium with pH values from 6.8 to 7.4. Bone metabolism was evaluated by measuring the rates of glycolysis (lactate production), protein synthesis ([3H]proline uptake), and collagen synthesis ([3H]proline hydroxylation). Tobramycin at the concentrations released from the beads (1.0-1.5 mg/ml) contributed to lowering the pH of the medium. At pH 7.4, the antibiotic produced as much as a 30, 39, and 48% decrease in glycolysis, protein synthesis, and collagen synthesis, respectively. Tibiae exposed to tobramycin for 3 days, followed by 2 days without the antibiotic, showed only a partial recovery from its toxic effects. Although tobramycin was relatively less toxic in an acidic environment, the overall metabolic activity of the bones was poorest when the tobramycin concentration was high (2.0 mg/ml) and pH was low (6.8). The results of this study support the following conclusions: (a) tobramycin at high concentrations is toxic to bone, (b) a combination of high tobramycin concentration and low pH in the bone microenvironment may greatly inhibit bone metabolism, and (c) treatment and prevention of osteomyelitis by means of tobramycin-impregnated beads may be augmented by preventing the pH from decreasing in traumatized areas.
Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Carolina 28232-2861, USA.
T
T
Murakami
H
H
Murakami
W K
WK
Ramp
E N
EN
Hanley
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002642:Chick Embryo; D003094:Collagen / Q000096:biosynthesis; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004347:Drug Interactions; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D016014:Linear Models; D008768:Methylmethacrylates; D008863:Microspheres; D014176:Protein Biosynthesis; D013977:Tibia / Q000166:cytology* / Q000378:metabolism; D014031:Tobramycin / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D003470:Culture Media; D008768:Methylmethacrylates; D003094:Collagen; D005947:Glucose; D014031:Tobramycin