Time-Dependent Effectiveness of Locally Applied Vancomycin Powder in a Contaminated Traumatic Orthopaedic Wound Model

Objectives: To evaluate the effectiveness of locally applied vancomycin powder at different times postinfection in a contaminated traumatic animal model. Methods: This study used an established segmental defect rat femur model contaminated with Staphylococcus aureus UAMS-1 followed by treatment at 6 or 24 hours postinfection. Three treatments were evaluated: debridement and irrigation alone (control group) or in combination with either vancomycin powder or vancomycin-impregnated poly(methyl methacrylate) beads. Serum vancomycin levels were determined at scheduled time points over 14 days; bone, surrounding muscle, and implants were harvested for bacterial and inflammatory analyses. Results: Locally applied vancomycin powder and impregnated beads significantly reduced bacteria both within the bone and implant when treatment was performed at 6 hours. Delaying treatment to 24 hours significantly reduced the therapeutic efficacy of locally applied vancomycin of both groups. Serum vancomycin levels were detectable in all animals treated with vancomycin powder at 24 hours, but absorption was negligible from beads. At 14 days, vancomycin was detectable in the surrounding musculature of all animals and in serum of 20% of animals treated with vancomycin powder. Conclusions: This study suggests that vancomycin powder is a promising adjunctive therapy for preventing infection in traumatic wounds when treatment is performed early. This time-dependent effectiveness of vancomycin powder is similar to that observed with systemic and other local delivery adjuncts, which is likely attributable to biofilm formation after contamination, conferring intrinsic recalcitrance to antimicrobials.

[1]  Jesse M. Ehrenfeld,et al.  Surgical site infection in orthopedic trauma: A case-control study evaluating risk factors and cost. , 2015, Journal of clinical orthopaedics and trauma.

[2]  L. Dahners,et al.  Local Injection of Aminoglycosides for Prophylaxis Against Infection in Open Fractures. , 2015, The Journal of bone and joint surgery. American volume.

[3]  C. Murray,et al.  Rifamycin Derivatives Are Effective Against Staphylococcal Biofilms In Vitro and Elutable From PMMA , 2015, Clinical orthopaedics and related research.

[4]  M. Bosse,et al.  Type III Open Tibia Fractures: Immediate Antibiotic Prophylaxis Minimizes Infection , 2014, Journal of orthopaedic trauma.

[5]  M. Kuchibhatla,et al.  Experience with intrawound vancomycin powder for posterior cervical fusion surgery. , 2015, Journal of neurosurgery. Spine.

[6]  M. Ogon,et al.  Does Intrawound Application of Vancomycin Influence Bone Regeneration in Spinal Fusion , 2014 .

[7]  V. Deviren,et al.  Local Intrawound Vancomycin Powder Decreases the Risk of Surgical Site Infections in Complex Adult Deformity Reconstruction: A Cost Analysis , 2014, Spine.

[8]  C. Murray,et al.  Human plasma enhances the expression of Staphylococcal microbial surface components recognizing adhesive matrix molecules promoting biofilm formation and increases antimicrobial tolerance In Vitro , 2014, BMC Research Notes.

[9]  G. Ehrlich,et al.  Can We Trust Intraoperative Culture Results in Nonunions? , 2014, Journal of orthopaedic trauma.

[10]  C. Murray,et al.  Local Antibiotic Delivery by a Bioabsorbable Gel Is Superior to PMMA Bead Depot in Reducing Infection in an Open Fracture Model , 2014, Journal of orthopaedic trauma.

[11]  J. Wenke,et al.  A versatile model of open-fracture infection , 2014, Bone & joint research.

[12]  G. Kumar,et al.  Prevention of Infection in the Treatment of One Thousand and Twenty-Five Open Fractures of Long Bones. Retrospective and Prospective Analyses , 2014 .

[13]  S. Rajasekaran,et al.  Effects of Using Intravenous Antibiotic Only Versus Local Intrawound Vancomycin Antibiotic Powder Application in Addition to Intravenous Antibiotics on Postoperative Infection in Spine Surgery in 907 Patients , 2013, Spine.

[14]  Kevin R. O'Neill,et al.  Comparative effectiveness and cost-benefit analysis of local application of vancomycin powder in posterior spinal fusion for spine trauma: clinical article. , 2013, Journal of neurosurgery. Spine.

[15]  Samuel K. Cho,et al.  Methods to decrease postoperative infections following posterior cervical spine surgery. , 2013, The Journal of bone and joint surgery. American volume.

[16]  K. Baldwin,et al.  Vancomycin prophylaxis of surgical site infection in clean orthopedic surgery. , 2013, Orthopedics.

[17]  C. Murray,et al.  Biofilm formation by clinical isolates and the implications in chronic infections , 2013, BMC Infectious Diseases.

[18]  J. Hsu,et al.  Negative Pressure Wound Therapy Reduces the Effectiveness of Traditional Local Antibiotic Depot in a Large Complex Musculoskeletal Wound Animal Model , 2012, Journal of orthopaedic trauma.

[19]  A. Mantalaris,et al.  In vitro and in vivo effects of antibiotics on bone cell metabolism and fracture healing , 2012, Expert opinion on drug safety.

[20]  P. Huddleston Intrawound Application of Vancomycin for Prophylaxis in Instrumented Thoracolumbar Fusions: Efficacy, Drug Levels, and Patient Outcomes , 2012 .

[21]  C. Murray,et al.  Early antibiotics and debridement independently reduce infection in an open fracture model. , 2012, The Journal of bone and joint surgery. British volume.

[22]  R. Molinari,et al.  Prophylactic intraoperative powdered vancomycin and postoperative deep spinal wound infection: 1,512 consecutive surgical cases over a 6-year period , 2012, European Spine Journal.

[23]  G. Ehrlich,et al.  Orthopaedic biofilm infections , 2011, Current orthopaedic practice.

[24]  T. Guda,et al.  Dual-Purpose Bone Grafts Improve Healing and Reduce Infection , 2011, Journal of orthopaedic trauma.

[25]  Kevin R. O'Neill,et al.  Reduced surgical site infections in patients undergoing posterior spinal stabilization of traumatic injuries using vancomycin powder. , 2011, The spine journal : official journal of the North American Spine Society.

[26]  Joseph C Wenke,et al.  Effect of various concentrations of antibiotics on osteogenic cell viability and activity , 2011, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[27]  C. Murray,et al.  Earlier debridement and antibiotic administration decrease infection. , 2012, Journal of surgical orthopaedic advances.

[28]  S. Guelcher,et al.  Sustained release of vancomycin from polyurethane scaffolds inhibits infection of bone wounds in a rat femoral segmental defect model. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[29]  S. Guelcher,et al.  Local Delivery of Tobramycin from Injectable Biodegradable Polyurethane Scaffolds , 2010, Journal of biomaterials science. Polymer edition.

[30]  W. Haggard,et al.  Locally-administered antibiotics in wounds in a limb. , 2009, The Journal of bone and joint surgery. British volume.

[31]  R. Castillo,et al.  Complications Following Limb-Threatening Lower Extremity Trauma , 2009, Journal of orthopaedic trauma.

[32]  R. Andersen,et al.  Short-term outcomes of severe open wartime tibial fractures treated with ring external fixation. , 2008, The Journal of bone and joint surgery. American volume.

[33]  T. Decoster,et al.  Antibiotic beads. , 2008, The Journal of the American Academy of Orthopaedic Surgeons.

[34]  B. Owens,et al.  Early wound irrigation improves the ability to remove bacteria. , 2007, The Journal of bone and joint surgery. American volume.

[35]  H. Vallier,et al.  Results and Outcomes After Operative Treatment of High-Energy Tibial Plafond Fractures , 2006, Foot & ankle international.

[36]  A. Hanssen Local antibiotic delivery vehicles in the treatment of musculoskeletal infection. , 2005, Clinical orthopaedics and related research.

[37]  C. A. Jones,et al.  The Effect of Time to Definitive Treatment on the Rate of Nonunion and Infection in Open Fractures , 2002, Journal of orthopaedic trauma.

[38]  W. Lew,et al.  Osteogenic protein‐1 induced bone formation in an infected segmental defect in the rat femur , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[39]  M. Chapman,et al.  Comparison of Antibiotic Beads and Intravenous Antibiotics in Open Fractures , 2000, Clinical orthopaedics and related research.

[40]  D. Seligson,et al.  Local antibiotic therapy for severe open fractures. A review of 1085 consecutive cases. , 1995, The Journal of bone and joint surgery. British volume.

[41]  D. Seligson,et al.  The antibiotic bead pouch technique. The management of severe compound fractures. , 1993, Clinical orthopaedics and related research.

[42]  S. Henry The antibiotic bead pouch technique , 1993 .

[43]  D. Seligson,et al.  The prophylactic use of antibiotic impregnated beads in open fractures. , 1990, The Journal of trauma.

[44]  M. Patzakis,et al.  Factors influencing infection rate in open fracture wounds. , 1989, Clinical orthopaedics and related research.

[45]  D. N. Williams,et al.  Problems in the management of type III (severe) open fractures: a new classification of type III open fractures. , 1984, The Journal of trauma.

[46]  R. Gustilo,et al.  OTD classic article review - Gustillo RB, Anderson JT (1976) Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses , 2002, The Journal of bone and joint surgery. American volume.