Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model

Abstract

Background Cathodic voltage-controlled electrical stimulation (CVCES) of titanium implants, either alone or combined with a short course of vancomycin, has previously been shown to reduce the bone and implant bacterial burden in a rodent model of methicillin-resistant Staphylococcus aureus (MRSA) implant-associated infection (IAI). Clinically, the goal is to achieve complete eradication of the IAI; therefore, the rationale for the present study was to evaluate the antimicrobial effects of combining CVCES with prolonged antibiotic therapy with the goal of decreasing the colony-forming units (CFUs) to undetectable levels.Questions/purposes (1) In an animal MRSA IAI model, does combining CVCES with prolonged vancomycin therapy decrease bacteria burden on the implant and surrounding bone to undetectable levels? (2) When used with prolonged vancomycin therapy, are two CVCES treatments more effective than one? (3) What are the longer term histologic effects (inflammation and granulation tissue) of CVCES on the surrounding tissue? Methods Twenty adult male Long-Evans rats with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, the rats were randomly divided into four groups of five: (1) VANCO: only vancomycin treatment (150 mg/ kg, subcutaneous, twice daily for 5 weeks); (2) VANCO + 1STIM: vancomycin treatment (same as the VANCO group) coupled with one CVCES treatment (À1.8 V for 1 hour on postoperative day [POD] 7); (3) VANCO + 2STIM: vancomycin treatment (same as the VANCO group) coupled with two CVCES treatments (À1.8 V for 1 hour on POD 7 and POD 21); or (4) CONT: no treatment. On POD 42, the implant, bone, and peripheral blood were collected for CFU enumeration and histological analysis, where we compared CFU/mL on the implants and bone among the groups. A pathologist, blinded to the experimental conditions, performed a semiquantitative analysis Clinical Orthopaedics and Related Research ®A Publication of The Association of Bone and Joint Surgeons® of inflammation and granulation tissue present in serial sections of the humeral head for animals in each experimental group. Results The VANCO + 1STIM decreased the implant bacterial burden (median = 0, range = 0-10 CFU/mL) when compared with CONT (median = 5.7 9 10 4 , range = 4.0 9 10 3 À8.0 9 10 5 CFU/mL; difference of medians = À5.6 9 10 4 ; p \ 0.001) and VANCO (median = 4.9 9 10 3 , range = 9.0 9 10 2 À2.1 9 10 4 CFU/mL; difference of medians = À4.9 9 10 3 ; p \ 0.001). The VANCO + 1STIM decreased the bone bacterial burden (median = 0, range = 0-0 CFU/mL) when compared with CONT (median = 1.3 9 10 2 , range = 0-9.4 9 10 2 CFU/ mL; difference of medians = À1.3 9 10 2 ; p \ 0.001) but was not different from VANCO (median = 0, range = 0-1.3 9 10 2 CFU/mL; difference of medians = 0; p = 0.210). The VANCO + 2STIM group had implant CFU (median = 0, range = 0-8.0 9 10 1 CFU/mL) and bone CFU (median = 0, range = 0-2.0 9 10 1 CFU/mL) that were not different from the VANCO + 1STIM treatment ...

Magnesium alloy AZ91 exhibits antimicrobial properties in vitro but not in vivo

“…A total of 12 adult Long‐Evans rats (males, 175–200 g/8–9 weeks) were acquired for the study. A previously described procedure was used to surgically place the AZ91 and cpTi implants . Following anesthesia administration using ketamine (50 mg/kg), xylazine (5 mg/kg), and acepromazine (1 mg/kg); the ventral periaxillary area was prepared by shaving, sterilizing with chlorhexidine and alcohol, and injection with local anesthetic (bupivacaine and lidocaine mix) subcutaneously.…”

“…A previously described procedure was used to surgically place the AZ91 and cpTi implants. 20,22,23 Following anesthesia administration using ketamine (50 mg/kg), xylazine (5 mg/kg), and acepromazine (1 mg/kg); the ventral periaxillary area was prepared by shaving, sterilizing with chlorhexidine and alcohol, and injection with local anesthetic (bupivacaine and lidocaine mix) subcutaneously. An oblique 1 cm skin incision was made over the shoulder joint, and sharp dissection through the subcutaneous fat and superficial muscle layers was carried down to expose the anterior portion of the rotator cuff [ Figure 1(A,B)].…”

Electrical stimulation disrupts biofilms in a human wound model and reveals the potential for monitoring treatment response with volatile biomarkers

“…While the use of ES in wound care management is well established, we did not identify any previous studies assessing the impact of ES on wound biofilms in a human ex vivo model. Investigations of ES against biofilms in vivo are also sparse, with only six studies to date having assessed the effect of ES on biofilms, with the majority showing positive outcomes; however, none of these studies investigated the direct effect of ES on cutaneous wound bacterial biofilms.…”

Development of durable microelectrodes for the detection of hydrogen peroxide and pH

“…A number of studies have showed promising results for the application of cathodic DC electrical stimulation for the treatment of implant-associated infections in both in vitro and in vivo models (Canty, Luke-Marshall, Campagnari, & Ehrensberger, 2017;Ehrensberger et al, 2015;Nodzo et al, 2015Nodzo et al, , 2016. Despite these results, the specific mechanism of these antimicrobial effects is still not fully understood.…”