title: Cathodic voltage-controlled electrical stimulation of titanium for prevention of methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii biofilm infections.
abstract: Antibiotic resistance of bacterial biofilms limits available treatment methods for implant-associated orthopaedic infections. This study evaluated the effects of applying cathodic voltage-controlled electrical stimulations (CVCES) of -1.5V and -1.8V (vs. Ag/AgCl) to coupons of commercially pure titanium (cpTi) incubated in cultures of methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii (A. baumannii) as a method of preventing bacterial attachment. Stimulations were applied for 2, 4, and 8h and coupon-associated and planktonic colony-forming units (CFU) were enumerated following stimulation. Compared to open circuit potential (OCP) controls, CVCES for 4h at -1.8V significantly reduced coupon-associated MRSA CFU by 99.9% (1.30×104vs. 4.45×107, p=0.047) and A. baumannii coupon-associated CFU by 99.9% (1.64×104vs. 5.93×107, p=0.001) and reduced planktonic CFU below detectable levels for both strains. CVCES at -1.8V for 8h also reduced coupon-associated and planktonic CFU below detectable levels for each strain. CVCES at -1.5V for 4 and 8h, and -1.8V for 2h did not result in clinically relevant reductions. For 4 and 8h stimulations, the current density was significantly higher for -1.8V than -1.5V, an effect directly related to the rate of water and oxygen reduction on the cpTi surface. This significantly increased the pH, a suspected influence in decreased CFU viability. The voltage-dependent electrochemical properties of cpTi likely contribute to the observed antimicrobial effects of CVCES. This study revealed that CVCES of titanium could prevent coupon-associated and planktonic CFU of Gram-positive MRSA and Gram-negative A. baumannii from reaching detectable levels in a magnitude-dependent and time-dependent manner.
  
  
  
  Periprosthetic joint infection is a devastating outcome of total joint arthroplasty and has led to increased patient morbidity and rising healthcare costs. Current treatments are limited by the growing prevalence of antimicrobial resistant biofilms. Therefore, there is a growing interest in the prevention of bacterial colonization of implants. Previous work has shown that cathodic voltage-controlled electrical stimulation (CVCES) of titanium is effective both in vitro and in vivo as an antimicrobial strategy to eradicate established implant-associated biofilm infections. The present study revealed that CVCES of titanium coupons also has utility in preventing coupon-associated and planktonic colony-forming units of Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative Acinetobacter baumannii from reaching detectable levels in a magnitude-dependent and time-dependent manner.
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, 445 Biomedical Research Building, 3435 Main Street, Buffalo, NY 14214, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Canty
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, 140 Biomedical Research Building, 3435 Main Street, Buffalo, NY 14214, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Luke-Marshall
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, 140 Biomedical Research Building, 3435 Main Street, Buffalo, NY 14214, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Campagnari
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, 445 Biomedical Research Building, 3435 Main Street, Buffalo, NY 14214, USA; Department of Orthopaedics, University at Buffalo, 445 Biomedical Research Building, 3435 Main Street, Buffalo, NY 14214, USA. Electronic address: mte@buffalo.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Ehrensberger
mesh_terms: D000151:Acinetobacter Infections / Q000382:microbiology / Q000517:prevention & control*; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D018441:Biofilms / Q000187:drug effects*; D015169:Colony Count, Microbial; D004558:Electric Stimulation; D004560:Electricity; D055664:Electrochemical Techniques; D004566:Electrodes; D006863:Hydrogen-Ion Concentration; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D014025:Titanium / Q000494:pharmacology*
chemical_list: D014025:Titanium
keywords: Antimicrobial; Biofilm; Electrical stimulation; Infection prevention; Titanium