Document Detail

Antibiotics for local delivery systems cause skeletal cell toxicity in vitro.
MedLine Citation:
PMID:  17572634     Owner:  NLM     Status:  MEDLINE    
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.
Valentin Antoci; Christopher S Adams; Noreen J Hickok; Irving M Shapiro; Javad Parvizi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Clinical orthopaedics and related research     Volume:  462     ISSN:  0009-921X     ISO Abbreviation:  Clin. Orthop. Relat. Res.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-10-16     Completed Date:  2007-11-01     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  0075674     Medline TA:  Clin Orthop Relat Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  200-6     Citation Subset:  AIM; IM    
Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA, USA.
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MeSH Terms
3T3 Cells
Anti-Bacterial Agents / administration & dosage*,  toxicity*
Biocompatible Materials
Bone Cements
Cell Count
Cell Membrane / drug effects
Cell Movement / drug effects
Cell Survival / drug effects
Chondrocytes / drug effects*,  enzymology,  pathology
Ciprofloxacin / toxicity
Dose-Response Relationship, Drug
Drug Delivery Systems*
L-Lactate Dehydrogenase / metabolism
Osteoblasts / drug effects*,  enzymology,  pathology
Tobramycin / toxicity
Vancomycin / toxicity
Grant Support
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Biocompatible Materials; 0/Bone Cements; 1404-90-6/Vancomycin; 32986-56-4/Tobramycin; 85721-33-1/Ciprofloxacin; EC Dehydrogenase

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