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 beca use of the potential for a low local pH in infected bone, the antibiot ic was tested in medium with pH values from 6.8 to 7.4. Bone metabolis m was evaluated by measuring the rates of glycolysis (lactate producti on), protein synthesis ([H-3]proline uptake), and collagen synthesis ( [H-3]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, r espectively. Tibiae exposed to tobramycin for 3 days, followed by 2 da ys without the antibiotic, showed only a partial recovery from its tox ic 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 combinatio n of high tobramycin concentration and low pH in the bone microenviron ment may greatly inhibit bone metabolism and (c) treatment and prevent ion of osteomyelitis by means of tobramycin-impregnated beads may be a ugmented by preventing the pH from decreasing in traumatized areas.