Kim, Won‐Jun

ABSTRACTIntraluminal infection of central venous catheters, used for long‐term treatment, can result in central line‐associated bloodstream infection (CLABSI). These infections can be challenging to prevent and treat due to formation of biofilms within catheter lumens, which shield bacteria from the human immune response and conventional antimicrobial therapies. Preventing bacterial colonization of catheter hubs is a strategy to prevent CLABSI. To address this, we developed a nonantibiotic, animal‐ready electrochemical catheter hub (e‐catheter hub), operated by a wearable, battery‐powered micropotentiostat (MP), that internally generates tunable hypochlorous acid (HOCl) for preventing intraluminal infection. The design evaluated three different electrode materials—titanium, platinum, and gold—for HOCl generation and biocidal activity, using working and counter electrodes of the same materials and a silver/silver chloride‐plated wire as a quasi‐reference electrode. e‐catheter hubs operated by MPs at 1.5 VAg/AgCl for 3 h generated HOCl, reducing Acinetobacter baumannii ATCC‐17978 below the detection limit (average reduction of 4.40 ± 0.05 log10 CFU/mL). The efficacy of e‐catheter hubs operated by MPs in generating HOCl and achieving biocidal activity is comparable to that of a commercial potentiostat. This study represents the first step in developing a localized, nonantibiotic strategy to mitigate CLABSI risk.

Abstract Background Wound biofilm infections impact ∼2% of the United States and at-risk individuals often have underlying morbidities such as diabetes. Antibiotics and topical approaches like debridement or silver dressings have had limited success, underscoring a need for strategies that efficiently target pathogens in wound beds. Methods We developed a hydrogen peroxide (H2O2) generating electrochemical bandage (e-bandage) composed of carbon fabric electrodes separated by cotton fabric with an Ag/AgCl reference electrode (RE) placed between cotton fabric layers. The e-bandage is controlled by a wearable micropotentiostat (MP); H2O2 is generated by O2 + 2H++ 2e- → H2O2. O2 is dissolved on a primary working electrode with negative polarity compared to the RE while a positively polarized secondary counter electrode generates H+ and e-. The H2O2 e-bandage/MP device has in vitro activity against mono- and dual-species bacterial and fungal biofilms. We showed that the H2O2 e-bandage decreased the burden of methicillin-resistant Staphylococcus aureus and/or Pseudomonas aeruginosa with difficult-to-treat resistance in a murine wound infection model. Given this, we initiated a H2O2 e-bandage safety assessment on healthy human skin. Here, testing of a non-polarized, circular (2 cm diameter) device pre-loaded with biocompatible hydrogel containing 0.9% NaCl is reported. Sterilized e-bandages assessed in a shelf-life study retained activity for two weeks. Adults with intact forearm skin were then recruited to the Clinical Research Trials Unit at the Mayo Clinic. Consented individuals had a non-polarized e-bandage covered by Tegaderm placed on their forearm. A MP enclosed in a biocompatible case was connected to the e-bandage and secured using skin tape. One day later, the device was removed and a follow-up phone call made six days later to assess for adverse effects. Results Three volunteers wearing a non-polarized H2O2 e-bandage experienced no discomfort, irritation, allergic reaction, or skin discoloration after device removal and seven days post device placement. Conclusion These preliminary studies combined with the previously performed murine bacterial biofilms work support further studies of this novel device for treating wound infections caused by antimicrobial resistant pathogens. Disclosures Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria

ABSTRACT Chronic wound infections can be difficult to treat and may lead to impaired healing and worsened patient outcomes. Novel treatment strategies are needed. This study evaluated the effects of intermittently produced hydrogen peroxide (H 2 O 2 ) and hypochlorous acid (HOCl), generated via an electrochemical bandage (e-bandage), against methicillin-resistant Staphylococcus aureus biofilms in an agar membrane biofilm model. By changing the working electrode potential, the e-bandage generated either HOCl (1.5 V Ag/AgCl ) or H 2 O 2 (−0.6 V Ag/AgCl ). The degree of biocidal activity of intermittent treatment with HOCl and H 2 O 2 correlated with HOCl treatment time; HOCl treatment durations of 0, 1.5, 3, 4.5, and 6 hours (with the rest of the 6-hour total treatment time devoted to H 2 O 2 generation) resulted in mean biofilm reductions of 1.36 ± 0.2, 2.22 ± 0.16, 3.46 ± 0.38, 4.63 ± 0.74, and 7.66 ± 0.5 log CFU/cm 2 , respectively, vs. non-polarized controls, respectively. However, application of H 2 O 2 immediately after HOCl treatment was detrimental to biofilm removal. For example, 3 hours HOCl treatment followed by 3 hours H 2 O 2 resulted in a 1.90 ± 0.84 log CFU/cm 2 lower mean biofilm reduction than 3 hours HOCl treatment followed by 3 hours non-polarization. HOCl generated over 3 hours exhibited biocidal activity for at least 7.5 hours after e-bandage operation ceased; 3 hours of HOCl generation followed by 7.5 hours of non-polarization resulted in a biofilm cell reduction of 7.92 ± 0.12 log CFU/cm 2 vs. non-polarized controls. Finally, intermittent treatment with HOCl (i.e., interspersed with periods of e-bandage non-polarization) for various intervals showed similar effects (approximately 6 log CFU/cm 2 reduction vs. non-polarized control) to continuous treatment with HOCl for 3 hours, followed by 3 hours of non-polarization. These findings suggest that timing and sequencing of HOCl and H 2 O 2 treatments are crucial for maximizing biofilm control when using an e-bandage strategy.