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

Abstract

Effective 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 × 10⁷ CFU/mL, p < 0.001) and a 99.97% reduction in the planktonic CFU (4.04 × 10⁴ vs. 1.26 × 10⁸ CFU/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.

Keywords: antimicrobial; biofilm; electrical stimulation; infection; titanium.