Cathodic voltage controlled electrical stimulation as treatment for eradication of Acinetobacter baumannii device related infection

摘要

Introduction: One of the primary mechanisms by which bacteria resist decontamination and persist in wounds and on implants is through the formation of biofilms. Bacteria in biofilms are highly resistant to antibiotics and necessitate that new strategies be developed for the eradication of implant-associated biofilm infections. Gram-negative Acinetobacter baumannii (A. baumannii) is a pathogen of increasing concern. Many A. baumannii isolates are multidrug-resistant and therefore, reliable and effective agents for the treatment of these infections are often lacking.This study sought to provide in-vivo proof of principle that application of cathodic voltage controlled electrical stimulation (CVCES) to titanium implants could reduce/eradicate implant-associated infections of A. baumannii. Methods: The Institutional Animal Care and Use Committee approved all protocols. As previously described , a titanium (cpTi) rod was implanted through the humeral head of 14 Long Evans rats and inoculated with approximately 105 colony forming units (CFU) of an A. baumannii clinical isolate (Ab307) to establish a localized implant-associated infection. On post-op day 7, animals were randomized to the control group (n=7) that received no treatment or the treatment group (n=7) that received CVCES as previously described Briefly, in the treatment group, electrical contact was made to the implant (working electrode) via a skin incision and a platinum wire (counter electrode) and an Ag/AgCI pellet (reference electrode) were placed at adjacent subcutaneous sites. The three electrodes were connected to a potentiostat to apply -1.8 V vs. Ag/AgCI to the implant for 1 hour. Following stimulation, the implant and humeral head were harvested for sonication and serial dilution plating to enumerate CFU. Peripheral blood samples were also collected for enumeration of CFU. Serial tissue sections of the humeral head, stained with hematoxylin and eosin, were also evaluated for histological effects of CVCES on the surrounding tissues. Student t-tests were used to compare bone and implant associated CFU between the two groups. Results: Figure 1 shows the CVCES treatment significantly reduced the implant-associated CFU by over 91% and bone-associated CFU by over 88%. All peripheral blood cultures were negative. The histological analysis showed no deleterious effects on the surrounding tissue as a result of the CVCES. Discussion: In this study, a 1-hour application of -1.8V CVCES to an infected cpTi implant in a rodent model significantly decreased the CFU of clinically relevant bacteria on both the implant and the surrounding bone tissue. The mechanism of this antimicrobial effect is not definitively known, but it is hypothesize to be related to the faradaic modification of the microenvironment adjacent to the implant. In addition, non-faradaic (charging) processes may also contribute to dispersing the bacteria from the implant. While further work is needed to clarify the mechanism of action, these outcomes for Gram-negative infections compliment recent reports showing CVCES is also effective at treating Gram-positive methicillin resistant Staphylococcal aureus implant infections . These broad-spectrum antimicrobial outcomes, combined with the lack of deleterious effect on the surrounding tissue, highlights the great potential CVCES has to introduce a paradigm shift in the treatment of implant associated infections.