Chronic pain at the implant site, "failed back surgery syndrome (FBSS)," is a common cause of spine fusion failure. Over the past five years, though, multiple studies have defined a clear link between FBSS and low levels of bacterial contamination on implant surfaces. In particular, these studies showed bacterial contamination in 40% of cases of hardware retrieved from FBSS patients who have otherwise no clinical signs of surgical site infection. In response to this clinical need, Orthobond has developed an antimicrobial pedicle screw implant system utilizing a high density of covalently bound quaternary ammonium compounds (QACs). This pedicle screw system has already demonstrated broad-spectrum antimicrobial efficacy and good biocompatibility; however, in order to commercialize the product, it is necessary to demonstrate that the antimicrobial implants will not promote the emergence of antibiotic-resistant bacteria. QACs are well-known for nearly a century in consumer products such as mouthwashes, shampoos and surface disinfectant sprays; they suffer few reports of bacterial resistance. However, when resistance to QACs does occur, it is through expression of one or more types of efflux pumps that work to remove QACs before they disrupt intracellular targets. We believe that surface-tethered QACs should not be subject to decreased efficacy by efflux pumps; these surface-bound molecules are expected to not enter the bacterium, but rather to act on its cell wall through positive-charge promoted mechanisms. The global aim of this proposed research also includes to implement rapid assays to determine the propensity for our QAC-treated pedicle screw implants to allow emergence of bacterial resistance to them and to other contact-based antimicrobials. This Phase 1 proposal consists of two specific aims, in brief:"¢ Aim 1 is to test whether repeated exposure of Orthobond antimicrobial pedicle screw surfaces to gram positive or gram negative bacteria results in decreased susceptibility of these bacteria to the implants or cross-resistance to commonly used antibiotics."¢ Aim 2 is to test if surface-bonding the QAC to the pedicle screw system obviates the resistance mechanism to dissolved QACs - expression of the QacA efflux pump gene. The design and implementation of these tests will allow for evaluation of the propensity of the Orthobondantimicrobial pedicle screw system to promote bacterial resistance. These studies will potentially provide critical data needed to market the antimicrobial pedicle screw system to physicians and their patients.
Public Health Relevance Statement: Project narrative: Orthobond is developing a covalent, non-eluting antimicrobial pedicle screw system. One of the biggest challenges in developing an antimicrobial implant is demonstrating that the device will not promote the emergence of antibiotic resistant bacteria. Here we propose to test our antimicrobial pedicles screw system with comprehensive in vitro test methods designed to determine 1) the likelihood of bacteria to become resistant to an antimicrobial which is attached to the surface of an implant, 2) The potential for cross-resistance to emerge against antibiotics which are commonly given to patients following spine surgery and 3) The potential for covalent attachment of a cationic antimicrobial to evade known resistance mechanisms.
Project Terms: Engineering, Genes, Goals, Gram-Negative Bacteria, Health, Laboratories, Methods, Microbiology, Mouthwash, Patients, Physicians, pressure, Research, Study Type, study design, Research Design, Risk, Spinal Column, Spine, backbone, Vertebral column, S aureus, S. aureus, Staph aureus, Staphylococcus aureus, surgical site infection, Surgical Wound Infection, Syndrome, Technology, Testing, Time, Titanium, Ti element, Work, Microbial Biofilms, biofilm, Antibiotic Resistance, Resistance to antibiotics, Resistant to antibiotics, antibiotic drug resistance, antibiotic resistant, chronic pain, bacterial resistance, Bacteria resistance, Bacteria resistant, Bacterial resistant, resistance to Bacteria, resistance to Bacterial, resistant to Bacteria, resistant to Bacterial, base, density, Site, Surface, Clinical, Phase, Survivors, Link, Evaluation, Susceptibility, Predisposition, Anatomic Abnormality, Anatomical Abnormality, Deformity, polymerization, Exposure to, fusion failure, Congenital failure of fusion, Protocol, Protocols documentation, System, Spinal, Operative Procedures, Surgical, Surgical Interventions, Surgical Procedure, surgery, Operative Surgical Procedures, Consult, quaternary ammonium compound, Surgeon, biocompatibility, biomaterial compatibility, consumer product, covalent bond, novel, Devices, Reporting, response, theories, Bacterial Antibiotic Resistance, antibiotic resistant bacteria, bacterial antibiotic resistant, bacterial resistance to antibiotic, Molecular Interaction, Binding, Address, Antimicrobial resistant, Resistance to antimicrobial, anti-microbial resistance, anti-microbial resistant, resistance to anti-microbial, resistant to anti-microbial, resistant to antimicrobial, Antimicrobial Resistance, Data, M.D., Doctor of Medicine, Ph.D., PhD, Doctor of Philosophy, Antimicrobial Effect, anti-microbial effect, Small Business Innovation Research Grant, SBIR, Small Business Innovation Research, resistance mechanism, resistant mechanism, Development, developmental, design, designing, novel strategies, new approaches, novel approaches, novel strategy, Coupling, innovation, innovate, innovative, Resistance, resistant, antimicrobial, anti-microbial, Implant, efflux pump, in vitro testing, materials science, Spine surgery, Spinal surgery, preclinical development, pre-clinical development, rapid test, rapid assay, rapid tests, Alloys, Antibiotics, Antibiotic Agents, Antibiotic Drugs, Miscellaneous Antibiotic, Back, Dorsum, Bacteria, Biological Assay, Assay, Bioassay, Biologic Assays, Cations, Cell Wall, Charge, Disinfectants, Pharmaceutical Preparations, Drugs, Medication, Pharmaceutic Preparations, drug/agent
