Ciprofloxacin Inhibition of Experimental Fracture-Healing*

Huddleston, P.M.; Steckelberg, James M.; Hanssen, Arlen D.; Rouse, Mark S.; Bolander, Mark E.; Patel, Robin

doi:10.2106/00004623-200002000-00002

Cited by 169 publications

(92 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Some of them might impair bone metabolism even in therapeutic serum concentrations. In vitro and animal experiments demonstrated a chondrotoxicity of fluoroquinolones (7,17) and an impairment of fracture repair in early stages (23). An inhibition of proliferation of osteoblast-like cells in vitro in low concentrations of rifampin was reported before (25a) and should be investigated further, because rifampin proved to be an effective agent for treating bacteria in biofilms, which is extremely important in the pathogenesis of bone and joint infections.…”

Section: Discussionmentioning

confidence: 71%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 71%

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

View full text Add to dashboard Cite

show abstract

“…The systemic use of fluoroquinolones impairs bone regeneration in vivo. [25][26][27] In addition to the dose at which antibiotics are toxic and inhibitory to bone production, it may be important to consider the degree to which these factors are affected. Antibiotics that resulted in >75% decreases at doses !200 mg/ml include the cephalosporins, the macrolide azithromycin, the rifamycin rifampin, the fluoroquinolones, and the tetracyclines (Fig.…”

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

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

show abstract

“…In an experimental study in rats, Gray and Elves (1981) observed that topically applied antibiotic powder was detrimental to the osteogenesis in fresh corticocancellous isograft. Subcutaneous injection of ciprofloxacin in an experimental rat model impaired fracture healing (Huddleston et al 2000). However, Petri (1984) showed that the osteogenic activity of cephalotin-and tobramycinsupplemented morselized cortical mineralized and demineralized bone was comparable to bone not supplemented with antibiotics.…”

Section: Discussionmentioning

confidence: 99%

Cortical allograft as a vehicle for antibiotic delivery

et al. 2005

View full text Add to dashboard Cite

Background Infection can be a devastating complication after implantation of a cortical bone allograft. The allograft could act as a vehicle for local antibiotic prophylaxis.Material and methods We studied the release of antibiotics in vitro from cortical bone allografts impregnated with antibiotics for different periods of time. We also studied whether cortical allografts impregnated with antibiotics could eradicate Staphylococcus aureus from an experimentally infected graft in vivo. In the in vitro study, pieces of cortical bone were impregnated with netilmicin, vancomycin, ciprofloxacin and rifampicin for 1 h, 10 h and 100 h. The antibiotics were eluted into phosphate-buffered saline (PBS) for 7 days, with daily transfer of the bone into fresh PBS. In the in vivo study, cortical allografts impregnated with antibiotics were placed in rats intramuscularly. 10 µL of an S. aureus suspension (0.6 × 10 5 CFU) was placed in the intramedullary cavity. After 15 days, the allografts were removed and examined for bacterial growth.Results The amount of antibiotics released in vitro was influenced by the time used for antibiotic impregnation of the bone. Allografts impregnated with netilmicin, vancomycin and rifampicin effectively eradicated perioperative contamination with S. aureus in vivo.Interpretation This study shows that a cortical bone allograft would be an effective vehicle for local antibiotic delivery.

show abstract

Ciprofloxacin Inhibition of Experimental Fracture-Healing*

Cited by 169 publications

References 25 publications

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

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

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

Cortical allograft as a vehicle for antibiotic delivery

Contact Info

Product

Resources

About