Topic
E-101 Solution
About: E-101 Solution is a research topic. Over the lifetime, 5 publications have been published within this topic receiving 15 citations.
Papers
TL;DR: E-101 shows potent and broad-spectrum in vitro activity against bacteria that are the causative pathogens ofSSIs, thereby providing the impetus to test its clinical utility in the prevention of SSIs.
Abstract: OBJECTIVES E-101 Solution (E-101) is a novel myeloperoxidase-mediated antimicrobial. It is composed of porcine myeloperoxidase (pMPO), glucose oxidase, glucose as the substrate and specific amino acids in an aqueous vehicle. E-101 is being developed for topical application directly into surgical wounds to prevent surgical site infections (SSIs). The in vitro activity of E-101 was investigated. METHODS MIC, MBC, time-kill and antimicrobial combination experiments were performed according to CLSI guidelines with modifications. Resistance selection studies were performed using a serial passage method. RESULTS E-101 showed MIC(90) values of 0.03, 0.5 and 0.5 mg pMPO/L for staphylococci (n = 140), streptococci (n = 95) and enterococci (n = 55), respectively. MIC(90) values ranged between 0.03-0.5 and ≤ 0.004-0.12 mg pMPO/L for Enterobacteriaceae (n = 148) and Gram-negative non-Enterobacteriaceae (n = 92) strains, respectively. There was no antimicrobial tolerance to E-101 for Staphylococcus aureus, Streptococcus agalactiae or Streptococcus pyogenes. Time-kill studies demonstrated a rapid (<30 min) bactericidal effect against S. aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa in a concentration-dependent and time-dependent manner. There was no evidence of stable resistance to E-101 among staphylococci, enterococci, E. coli or P. aeruginosa strains and no evidence of E-101 interaction with antibiotics commonly used in clinical medicine. Conclusions E-101 shows potent and broad-spectrum in vitro activity against bacteria that are the causative pathogens of SSIs, thereby providing the impetus to test its clinical utility in the prevention of SSIs.
12 citations
TL;DR: The findings suggest that the primary site where E-101 solution exerts microbicidal action is the cell membrane, by inactivation of essential cell membrane components.
Abstract: E-101 solution is a first-in-class myeloperoxidase-mediated antimicrobial developed for topical application. It is composed of porcine myeloperoxidase (pMPO), glucose oxidase (GO), glucose, sodium chloride, and specific amino acids in an aqueous solution. Once activated, the reactive species hydrogen peroxide (H2O2), hypochlorous acid, and singlet oxygen are generated. We evaluated the treatment effects of E-101 solution and its oxidative products on ultrastructure changes and microbicidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli Time-kill and transmission electron microscopy studies were also performed using formulations with pMPO or GO omitted. The glutathione membrane protection assay was used to study the neutralization of reactive oxygen species. The potency of E-101 solution was also measured in the presence of serum and whole blood by MIC and minimal bactericidal concentration (MBC) determinations. E-101 solution demonstrated rapid bactericidal activity and ultracellular changes in MRSA and E. coli cells. When pMPO was omitted, high levels of H2O2 generated from GO and glucose demonstrated slow microbicidal activity with minimal cellular damage. When GO was omitted from the formulation, no antimicrobial activity or cellular damage was observed. Protection from exposure to E-101 solution reactive oxygen species in the glutathione protection assay was competitive and temporary. E-101 solution maintained its antimicrobial activity in the presence of inhibitory substances, such as serum and whole blood. E-101 solution is a potent myeloperoxidase enzyme system with multiple oxidative mechanisms of action. Our findings suggest that the primary site where E-101 solution exerts microbicidal action is the cell membrane, by inactivation of essential cell membrane components.
7 citations
TL;DR: The findings suggest the primary site that E-101solution exerts microbicidal action is the cell membrane by inactivation of essential cell membrane components.
Abstract: E-101 Solution is a first in class myeloperoxidase-mediated antimicrobial developed for topical application. It is composed of porcine myeloperoxidase (pMPO), glucose oxidase (GO), glucose, sodium chloride, and specific amino acids in an aqueous vehicle. Once activated, the reactive species hydrogen peroxide (H2O2), hypochlorous acid and singlet oxygen are generated. We evaluated the treatment effects of E-101 solution and its oxidative products on ultrastucture changes and microbicidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Time kill and transmission electron microscopy studies were performed using formulations with pMPO or GO omitted. The glutathione membrane protection assay was used to study the neutralization of reactive oxygen species. The potency of E-101 solution was also measured in the presence of serum and whole blood by MIC and MBC determinations. E-101 solution demonstrated rapid bactericidal activity and ultracellular changes in MRSA and E. coli cells. When pMPO was omitted, high levels of H2O2 generated from GO and glucose demonstrated slow microbicidal activity with minimal cellular damage. When GO was omitted from the formulation no antimicrobial activity or cellular damage was observed. Protection from exposure to E-101 solution reactive oxygen species in the glutathione protection assay was competitive and temporary. E-101 solution maintained its antimicrobial activity in the presence of inhibitory substances such as serum and whole blood. E-101 solution is a potent myeloperoxidase enzyme system with multiple oxidative mechanisms of action. Our findings suggest the primary site that E-101 solution exerts microbicidal action is the cell membrane by inactivation of essential cell membrane components.
5 citations
28 Oct 2008
1 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2019 | 1 |
| 2018 | 1 |
| 2011 | 1 |
| 2008 | 2 |