Effect of Cefazolin and Vancomycin on Osteoblasts In Vitro

Edin, Matthew L.; Miclau, Theodore; Lester, Gayle E.; Lindsey, Ronald W.; Dahners, Laurence E.

doi:10.1097/00003086-199612000-00027

Cited by 199 publications

(149 citation statements)

References 24 publications

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“…Despite the difference in treatment duration between the current and previous studies, our data are consistent with several other studies in which shorter time periods were used and/or difference cell types were studied. 12,14,15,[17][18][19][20][21][22][23] This similarity both adds validity to our data and suggests that the negative effects imparted by high levels of antibiotics in this study may be a result of changes that occur at early time points.…”

Section: Discussionsupporting

confidence: 77%

“…18 Previous studies showed a potential benefit of antibiotics on osteogenic potential, especially the cephalosporins. For example, the cephalosporin cefurotoxime has the potential to increase ALP activity and proliferation, 23 and a cefazolin-loaded biodegradable polypeptide multilayer nanofilm improved osteoblast viability and proliferation.…”

Section: Discussionmentioning

confidence: 99%

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Effect of various concentrations of antibiotics on osteogenic cell viability and activity

Rathbone

Cross

Brown

et al. 2011

Journal Orthopaedic Research

290

236

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Infection is a common complication of open fractures. Systemic antibiotics often cause adverse events before eradication of infected bone occurs. The local delivery of antibiotics and the use of implants that deliver both growth factors and antimicrobials are ways to circumvent systemic toxicity while decreasing infection and to reach extremely high levels required to treat bacterial biofilms. When choosing an antibiotic for a local delivery system, one should consider the effect that the antibiotic has on cell viability and osteogenic activity. To address this concern, osteoblasts were treated with 21 different antibiotics over 8 concentrations from 0 to 5,000 mg/ml. Osteoblast deoxyribonucleic acid content and alkaline phosphatase activity (ALP) were measured to determine cell number and osteogenic activity, respectively. Antibiotics that caused the greatest decrement include rifampin, minocycline, doxycycline, nafcillin, penicillin, ciprofloxacin, colistin methanesulfonate, and gentamicin; their cell number and ALP were significantly less than control at drug concentrations 200 mg/ ml. Conversely, amikacin, tobramycin, and vancomycin were the least cytotoxic and did not appreciably affect cell number and ALP until very high concentrations were used. This comprehensive evaluation of numerous antibiotics' effects on osteoblast viability and activity will enable clinicians and researchers to choose the optimal antibiotic for treatment of infection and maintenance of healthy host bone. ß

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Effect of various concentrations of antibiotics on osteogenic cell viability and activity

Rathbone

Cross

Brown

et al. 2011

Journal Orthopaedic Research

290

236

View full text Add to dashboard Cite

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“…Some of our observed cytotoxic and cytostatic effects of clindamycin, macrolides, fluoroquinolones, linezolid, chloramphenicol, rifampin, and tetracycline on PHO can be explained by an impairment of mitochondrial energetics, whereas the inhibitors of the bacterial cell wall syntheses (with the exception of cefazolin with an unknown eukaryotic target [16]) and aminoglycosides displayed no effect on PHO because of ab- sence of a specific target or because they could not enter the cells in the absence of a specific receptor (34,43). In contrast, chloramphenicol and linezolid increased the lactate production comparable to the specific inhibitors of the respiratory chain presumably by inhibition of mitochondrial protein synthesis, which was actually shown in vitro for chloramphenicol (30,39).…”

Section: Discussionmentioning

confidence: 94%

Influence on Mitochondria and Cytotoxicity of Different Antibiotics Administered in High Concentrations on Primary Human Osteoblasts and Cell Lines

Duewelhenke

Krut

Eysel

2007

Antimicrob Agents Chemother

173

138

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Osteomyelitis, osteitis, spondylodiscitis, septic arthritis, and prosthetic joint infections still represent the worst complications of orthopedic surgery and traumatology. Successful treatment requires, besides surgical débridement, long-term systemic and high-concentration local antibiotic therapy, with possible local antibiotic concentrations of 100 g/ml and more. In this study, we investigated the effect of 20 different antibiotics on primary human osteoblasts (PHO), the osteosarcoma cell line MG63, and the epithelial cell line HeLa. High concentrations of fluoroquinolones, macrolides, clindamycin, chloramphenicol, rifampin, tetracycline, and linezolid during 48 h of incubation inhibited proliferation and metabolic activity, whereas aminoglycosides and inhibitors of bacterial cell wall synthesis did not. Twenty percent inhibitory concentrations for proliferation of PHO were determined as 20 to 40 g/ml for macrolides, clindamycin, and rifampin, 60 to 80 g/ml for chloramphenicol, tetracylin, and fluoroquinolones, and 240 g/ml for linezolid. The proliferation of the cell lines was always less inhibited. We established the measurement of extracellular lactate concentration as an indicator of glycolysis using inhibitors of the respiratory chain (antimycin A, rotenone, and sodium azide) and glycolysis (iodoacetic acid) as reference compounds, whereas inhibition of the respiratory chain increased and inhibition of glycolysis decreased lactate production. The measurement of extracellular lactate concentration revealed that fluoroquinolones, macrolides, clindamycin, rifampin, tetracycline, and especially chloramphenicol and linezolid impaired mitochondrial energetics in high concentrations. This explains partly the observed inhibition of metabolic activity and proliferation in our experiments. Because of differences in the energy metabolism, PHO provided a more sensitive model for orthopedic antibiotic usage than stable cell lines.

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“…Larger tendons also eluted drug for longer periods of time; however, the differences in amounts of vancomycin released after 1 hour were small. Despite this difference, vancomycin release during the first 10 minutes and cumulatively during the 24-hour period was lower than the concentration ([ 1000 lg/mL) shown to be toxic to osteoblasts [6]. Therefore, in addition to decreasing infection rates, vancomycin released from tendons should not affect healing time.…”

Section: Discussionmentioning

confidence: 94%

“…Vancomycin has been used routinely for local antibiotic infusion into joints, and in vitro studies have provided some evidence of its low osteoclast and chondrocyte toxicity [2,6] We therefore characterized the elution of vancomycin from tendons treated using the same above-mentioned protocol currently undergoing trials during surgery and determined what parameters influenced the rate and extent of observed drug elution. The primary aim was to evaluate the effect of rinsing on the rate and extent of vancomycin elution from tendon tissue.…”

Section: Introductionmentioning

confidence: 99%

The In Vitro Elution Characteristics of Vancomycin from Tendons

Grayson

Grant

Dukie

et al. 2011

Clinical Orthopaedics &Amp; Related Research

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Background Infection after ACL reconstruction is uncommon but catastrophic. Prophylactic graft saturation in vancomycin reportedly reduces infection rates. Questions/purposes We characterized vancomycin elution from soaked tendons. Specifically, the effect of rinsing was studied. We also determined how vancomycin concentration in the soak solution and tendon dimension influenced this elution rate, and examined whether the vancomycin amount released was lower than osteoblast and chondroblast toxic concentrations. Methods Bovine tendons were wrapped in sterile gauze swabs presoaked with 5-, 2.5-, or 1.25-mg/mL vancomycin solutions. After 10 minutes, rinsed and unrinsed tendons were placed in 100 mL agitated 37°C phosphate-buffered saline (PBS). One-milliliter samples taken at 10 minutes and 1, 6, 12, 24, and 72 hours were analyzed by highperformance liquid chromatography. ResultsThe maximum elution rate occurred between 10 minutes and 1 hour, with no lag between experiment initiation and drug appearance in the solution. Rinsing affected the initial amount in solution but had little influence on drug release after 10 minutes. Vancomycin diffusion rates were dependent on soak solution concentration at all sampling intervals. The vancomycin amount released or eluted did not increase after the 1-hour interval. At 24 hours, concentrations were 45 ± 12, 16 ± 1, and 9 ± 3 lg/mL for the 5-, 2.5-, and 1.25-mg/mL solutions, respectively. Higher elution rates were observed in largervolume tendons. Conclusions Soaked tendon grafts can act as reservoirs for vancomycin, with the amount released and elution profile dependent on rinsing, tendon volume, and soak solution concentration. Vancomycin elution was lower than previously reported osteoblast and chondroblast toxicity concentrations and above the minimum inhibitory concentration for Staphylococcus. Clinical Relevance Presoaking ACL reconstruction autografts with vancomycin may reduce the risk of ACL reconstruction infection without the risk of local or general toxicity.

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Effect of Cefazolin and Vancomycin on Osteoblasts In Vitro

Cited by 199 publications

References 24 publications

Effect of various concentrations of antibiotics on osteogenic cell viability and activity

Effect of various concentrations of antibiotics on osteogenic cell viability and activity

Influence on Mitochondria and Cytotoxicity of Different Antibiotics Administered in High Concentrations on Primary Human Osteoblasts and Cell Lines

The In Vitro Elution Characteristics of Vancomycin from Tendons

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