Mohamed, Abdelrhman

Abstract Aims As antimicrobial resistance is on the rise, treating chronic wound infections is becoming more complex. The presence of biofilms in wound beds contributes to this challenge. Here, the activity of a novel hypochlorous acid (HOCl) producing electrochemical bandage (e-bandage) against monospecies and dual-species bacterial biofilms formed by bacteria commonly found in wound infections was assessed. Methods and results The system was controlled by a wearable potentiostat powered by a 3V lithium-ion battery and maintaining a constant voltage of + 1.5V Ag/AgCl, allowing continuous generation of HOCl. A total of 19 monospecies and 10 dual-species bacterial biofilms grown on polycarbonate membranes placed on tryptic soy agar (TSA) plates were used as wound biofilm models, with HOCl producing e-bandages placed over the biofilms. Viable cell counts were quantified after e-bandages were continuously polarized for 2, 4, 6, and 12 hours. Time-dependent reductions in colony forming units (CFUs) were observed for all studied isolates. After 12 hours, average CFU reductions of 7.75 ± 1.37 and 7.74 ± 0.60 log10 CFU/cm2 were observed for monospecies and dual-species biofilms, respectively. Conclusions HOCl producing e-bandages reduce viable cell counts of in vitro monospecies and dual-species bacterial biofilms in a time-dependent manner in vitro. After 12 hours, >99.999% reduction in cell viability was observed for both monospecies and dual-species biofilms.

AbstractBiofilms formed by antibiotic‐resistant bacteria in wound beds challenge the treatment of wound infections. In this work, the activity of a novel electrochemical bandage (e‐bandage) composed of carbon fabric and controlled by a wearable potentiostat, designed to continuously deliver low amounts of hydrogen peroxide (H2O2), is evaluated against methicillin‐resistant Staphylococcus aureus (MRSA), multidrug‐resistant Pseudomonas aeruginosa (MDR‐PA) and mixed‐species (MRSA and MDR‐PA) wound infections. Wounds created on Swiss Webster mice are infected with the above‐named bacteria and biofilms allow to establish in wound beds for 3 days. e‐Bandages, which electrochemically reduce dissolved oxygen to H2O2 when polarized at −0.6 VAg/AgCl, are placed atop infected wound beds and polarized continuously for 48 h. Polarized e‐bandage treatment results in significant reductions (p <0.001) of both monospecies and mixed‐species wound infections. After e‐bandage treatment, electron microscopy shows degradation of bacterial cells, and histopathology shows no obvious alterations to the inflammatory host response. Blood biochemistries show no abnormalities. Taken all together, results of this work suggest that the described H2O2‐producing e‐bandage can reduce in vivo MRSA, MDR‐PA, and mixed‐species wound biofilms, and should be further developed as a potential antibiotic‐free strategy for treatment of wound infections.

The antibiofilm activity of a hypochlorous acid (HOCl)-producing electrochemical bandage (e-bandage) was assessed against 14 yeast isolates in vitro . The evaluated e-bandage was polarized at +1.5 V Ag/AgCl to allow continuous production of HOCl.

Chronic wound biofilm infections represent a major clinical challenge which results in a substantial burden to patients and healthcare systems. Treatment with topical antibiotics is oftentimes ineffective as a result of antibiotic‐resistant microorganisms and biofilm‐specific antibiotic tolerance. Use of biocides such as hypochlorous acid (HOCl) has gained increasing attention due to the lack of known resistance mechanisms. An HOCl‐generating electrochemical bandage (e‐bandage) is designed that delivers HOCl continuously at low concentrations targeting infected wound beds in a similar manner to adhesive antimicrobial wound dressings. A battery‐operated wearable potentiostat is developed that controls the e‐bandage electrodes at potentials suitable for HOCl generation. It is demonstrated that e‐bandage treatment is tunable by changing the applied potential. HOCl generation on electrode surfaces is verified using microelectrodes. The developed e‐bandage shows time‐dependent responses against in vitro Acinetobacter baumannii and Staphylococcus aureus biofilms, reducing viable cells to nondetectable levels within 6 and 12 h of treatment, respectively. The developed e‐bandage should be further evaluated as an alternative to topical antibiotics to treat wound biofilm infections.

AbstractThe activity of a hypochlorous acid‐producing electrochemical bandage (e‐bandage) in preventing methicillin‐resistant Staphylococcus aureus infection (MRSA) infection and removing biofilms formed by MRSA was assessed using a porcine explant biofilm model. e‐Bandages inhibited S. aureus infection (p = 0.029) after 12 h (h) of exposure and reduced 3‐day biofilm viable cell counts after 6, 12, and 24 h exposures (p = 0.029). Needle‐type microelectrodes were used to assess HOCl concentrations in explant tissue as a result of e‐bandage treatment; toxicity associated with e‐bandage treatment was evaluated. HOCl concentrations in infected and uninfected explant tissue varied between 30 and 80 µM, decreasing with increasing distance from the e‐bandage. Eukaryotic cell viability was reduced by an average of 71% and 65% in fresh and day 3‐old explants, respectively, when compared to explants exposed to nonpolarized e‐bandages. HOCl e‐bandages are a promising technology that can be further developed as an antibiotic‐free treatment for wound biofilm infections.

Abstract Aims Effects of H2O2 producing electrochemical-bandages (e-bandages) on methicillin-resistant Staphylococcus aureus colonization and biofilm removal were assessed using a porcine explant biofilm model. Transport of H2O2 produced from the e-bandage into explant tissue and associated potential toxicity were evaluated. Methods and Results Viable prokaryotic cells from infected explants were quantified after 48 h treatment with e-bandages in three ex vivo S. aureus infection models: (1) reducing colonization, (2) removing young biofilms and (3) removing mature biofilms. H2O2 concentration-depth profiles in explants/biofilms were measured using microelectrodes. Reductions in eukaryotic cell viability of polarized and nonpolarized noninfected explants were compared. e-Bandages effectively reduced S. aureus colonization (p = 0.029) and reduced the viable prokaryotic cell concentrations of young biofilms (p = 0.029) with limited effects on mature biofilms (p &gt; 0.1). H2O2 penetrated biofilms and explants and reduced eukaryotic cell viability by 32–44% compared to nonpolarized explants. Conclusions H2O2 producing e-bandages were most active when used to reduce colonization and remove young biofilms rather than to remove mature biofilms. Significance and Impact of Study The described e-bandages reduced S. aureus colonization and young S. aureus biofilms in a porcine explant wound model, supporting their further development as an antibiotic-free alternative for managing biofilm infections.

Wound infections are caused by bacteria and/or fungi. The presence of fungal biofilms in wound beds presents a unique challenge, as fungal biofilms may be difficult to eradicate.

Abstract Background Central-line associated bloodstream infection (CLABSI) contributes to mortality and cost. While aseptic dressings and antibiotic-impregnated catheters can prevent extraluminal infections, intraluminal infections remain a source of CLABSIs with limited prevention options. Methods In this proof-of-concept study, an electrochemical intravascular catheter (e-catheter) prototype capable of electrochemically generating hypochlorous acid intraluminally on the surface of platinum electrodes polarized at a constant potential of 1.5 VAg/AgCl was developed. After 24h of pre-polarization at 1.5 VAg/AgCl, their activity was tested by inoculating four clinical isolates derived from catheter-related infections, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium and Escherichia coli. Figure 1. In vitro catheter and e-catheter models. Results E-catheters generated a mean HOCl concentration of 15.86±4.03 μM and had a mean pH of 6.14±0.79. e-catheters prevented infections with all four species, with an average reduction of 8.41±0.61 log10 CFU/mL at 48h compared to controls. Figure 3. Measurement of pH and HOCl at 48 hours in polarized e-catheters. Each dot represents a replicate; bars represent means. Figure 4. Prevention of infection after 48 hours of polarization (24 hours of infections) using e-catheters (polarized and non-polarized) compared to blank catheters. * indicates statistically significant reduction of cell counts in polarized e-catheter compared to blank catheter (p &lt;0.05). Conclusion Polarized e-catheters which generate low amounts of HOCl continuously should be further developed to prevent intraluminal infection. Disclosures Haluk Beyenal, Ph.D, patent (Other Financial or Material Support, HB holds a patent: Beyenal H CD, Fransson BA, Sultana ST. . 2018. Electrochemical reduction or prevention of infections. U.S. patent 20180207301A1, international patent WO/2017/011635.) Robin Patel, MD, 1928 Diagnostics (Consultant)BioFire Diagnostics (Grant/Research Support)ContraFect Corporation (Grant/Research Support)Curetis (Consultant)Hylomorph AG (Grant/Research Support)IDSA (Other Financial or Material Support, Editor's Stipend)Infectious Diseases Board Review Course (Other Financial or Material Support, Honoraria)Mammoth Biosciences (Consultant)NBME (Other Financial or Material Support, Honoraria)Netflix (Consultant)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)PhAST (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Patent Royalties)Selux Diagnostics (Consultant)Shionogi & Co., Ltd. (Grant/Research Support)Specific Technologies (Consultant)TenNor Therapeutics Limited (Grant/Research Support)Torus Biosystems (Consultant)Up-to-Date (Other Financial or Material Support, Honoraria) Robin Patel, MD, BioFire (Individual(s) Involved: Self): Grant/Research Support; Contrafect (Individual(s) Involved: Self): Grant/Research Support; IDSA (Individual(s) Involved: Self): Editor's stipend; NBME, Up-to-Date and the Infectious Diseases Board Review Course (Individual(s) Involved: Self): Honoraria; Netflix (Individual(s) Involved: Self): Consultant; TenNor Therapeutics Limited (Individual(s) Involved: Self): Grant/Research Support; to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences and Qvella (Individual(s) Involved: Self): Consultant

Catheter-related infections constitute an economic and mortality burden in health care. Several options are available to reduce the risk of infection, but only a few focus on preventing intraluminal infection, which occurs in long-term catheters, most often used for dialysis, prolonged treatment, or chemotherapy.

AbstractChronic wound infections caused by biofilm‐forming microorganisms represent a major burden to healthcare systems. Treatment of chronic wound infections using conventional antibiotics is often ineffective due to the presence of bacteria with acquired antibiotic resistance and biofilm‐associated antibiotic tolerance. We previously developed an electrochemical scaffold that generates hydrogen peroxide (H2O2) at low concentrations in the vicinity of biofilms. The goal of this study was to transition our electrochemical scaffold into an H2O2‐generating electrochemical bandage (e‐bandage) that can be used in vivo. The developed e‐bandage uses a xanthan gum‐based hydrogel to maintain electrolytic conductivity between e‐bandage electrodes and biofilms. The e‐bandage is controlled using a lightweight, battery‐powered wearable potentiostat suitable for use in animal experiments. We show that e‐bandage treatment reduced colony‐forming units of Acinetobacter buamannii biofilms (treatment vs. control) in 12 h (7.32 ± 1.70 vs. 9.73 ± 0.09 log10[CFU/cm2]) and 24 h (4.10 ± 12.64 vs. 9.78 ± 0.08 log10[CFU/cm2]) treatments, with 48 h treatment reducing viable cells below the limit of detection of quantitative and broth cultures. The developed H2O2‐generating e‐bandage was effective against in vitro A. baumannii biofilms and should be further evaluated and developed as a potential alternative to topical antibiotic treatment of wound infections.