In vitro and in vivo assessment of extended duration cathodic voltage‐controlled electrical stimulation for treatment of orthopedic implant‐associated infections

Abstract

AbstractEffective treatment of orthopedic implant‐associated infections (IAIs) remains a clinical challenge. The in vitro and in vivo studies presented herein evaluated the antimicrobial effects of applying cathodic voltage‐controlled electrical stimulation (CVCES) to titanium implants inoculated with preformed bacterial biofilms of methicillin‐resistant Staphylococcus aureus (MRSA). The in vitro studies showed that combining vancomycin therapy (500 µg/mL) with application of CVCES at −1.75 V (all voltages are with respect to Ag/AgCl unless otherwise stated) for 24 h resulted in 99.98% reduction in the coupon‐associated MRSA colony‐forming units (CFUs) (3.38 × 103 vs. 2.14 × 107CFU/mL, p < 0.001) and a 99.97% reduction in the planktonic CFU (4.04 × 104 vs. 1.26 × 108CFU/mL, p < 0.001) as compared with the no treatment control samples. The in vivo studies utilized a rodent model of MRSA IAIs and showed a combination of vancomycin therapy (150 mg/kg twice daily) with CVCES of −1.75 V for 24 h had significant reductions in the implant associated CFU (1.42 × 101 vs. 1.2 × 106 CFU/mL, p < 0.003) and bone CFU (5.29 × 101 vs. 4.48 × 106 CFU/mL, p < 0.003) as compared with the untreated control animals. Importantly, the combined 24 h CVCES and antibiotic treatments resulted in no implant‐associated MRSA CFU enumerated in 83% of the animals (five out of six animals) and no bone‐associated MRSA CFU enumerated in 50% of the animals (three out of six animals). Overall, the outcomes of this study have shown that extended duration CVCES therapy is an effective adjunctive therapy to eradicate IAIs.