OBJECTIVE: To investigate the toxic effect of gentamicin at the high concentrations that can be achieved by local administration in the management of bone infection. DESIGN: Randomized, prospective study in cultured cells, with drug exposure duration of 4 days. SETTING: Cell culture in Dulbecco's modification of Eagle's minimal essential medium with supplements at 37 degrees C in air:CO2 (v:v, 95:5). MATERIALS: Human osteoblastlike cells derived from cancellous bone collected from four adult patients without systemic disease during total hip replacement were cultured in antibiotic-free medium for 4 weeks. INTERVENTION: The cultured cells were exposed to media containing various concentrations of gentamicin (0-1000 microg/mL) for 4 days. MAIN OUTCOME MEASUREMENTS: Alkaline phosphatase activity, total DNA, and 3H-thymidine incorporation. RESULT: Alkaline phosphatase activity was significantly decreased (p < 0.05) in all of the cultures at gentamicin concentrations of 100 microg/mL and above. 3H-thymidine incorporation was also decreased (p < 0.05) in three out of four cultures at 100 microg/mL and above. Total DNA was significantly decreased (p < 0.05) at 700 microg/mL and above. CONCLUSION: Gentamicin, at high concentrations, as achieved following topical application, inhibits cell proliferation in vitro and, therefore, may be detrimental to the repair process in vivo.
OBJECTIVE: To investigate the toxic effect of gentamicin at the high concentrations that can be achieved by local administration in the management of bone infection. DESIGN: Randomized, prospective study in cultured cells, with drug exposure duration of 4 days. SETTING: Cell culture in Dulbecco's modification of Eagle's minimal essential medium with supplements at 37 degrees C in air:CO2 (v:v, 95:5). MATERIALS: Human osteoblastlike cells derived from cancellous bone collected from four adult patients without systemic disease during total hip replacement were cultured in antibiotic-free medium for 4 weeks. INTERVENTION: The cultured cells were exposed to media containing various concentrations of gentamicin (0-1000 microg/mL) for 4 days. MAIN OUTCOME MEASUREMENTS: Alkaline phosphatase activity, total DNA, and 3H-thymidine incorporation. RESULT: Alkaline phosphatase activity was significantly decreased (p < 0.05) in all of the cultures at gentamicin concentrations of 100 microg/mL and above. 3H-thymidine incorporation was also decreased (p < 0.05) in three out of four cultures at 100 microg/mL and above. Total DNA was significantly decreased (p < 0.05) at 700 microg/mL and above. CONCLUSION:Gentamicin, at high concentrations, as achieved following topical application, inhibits cell proliferation in vitro and, therefore, may be detrimental to the repair process in vivo.
Authors: Craig Winkler; Joel Dennison; Adam Wooldridge; Eneko Larumbe; Cyrus Caroom; Mark Jenkins; George Brindley Journal: J Clin Orthop Trauma Date: 2017-08-24
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