In vitro antibacterial activity of E-101 Solution, a novel myeloperoxidase-mediated antimicrobial, against Gram-positive and Gram-negative pathogens

• Published in: Journal of antimicrobial chemotherapy Vol. 66; no. 2; pp. 335 - 342
• Main Authors: DENYS, Gerald A, GROVER, Parveen, O'HANLEY, Peter, STEPHENS, Jackson T
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-02-2011; Oxford Publishing Limited (England)
• Subjects: Amino acids; Anti-Infective Agents - pharmacology; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteriology; Biological and medical sciences; Drug Resistance, Bacterial; Enterobacteriaceae; Enterococcus faecalis; Enzymes; Escherichia coli; General aspects; Gram-negative bacteria; Gram-Negative Bacteria - drug effects; Gram-positive bacteria; Gram-Positive Bacteria - drug effects; Human infectious diseases. Experimental studies and models; Infectious diseases; Medical sciences; Microbial Sensitivity Tests; Peroxidase - pharmacology; Pharmacology. Drug treatments; Pseudomonas aeruginosa; Staphylococcus aureus; Streptococcus agalactiae; Streptococcus pyogenes; Surgical wound; Nosocomial infection; Oxygen; Enzyme; surgical site infections; In vitro; Biological activity; Antimicrobial agent; Local administration; Treatment; Peroxidases; singlet oxygen; Gram positive bacteria; Pathogenic; Peroxidase; Oxidoreductases; Antibacterial agent; Topical administration; therapeutic enzyme system; topical antimicrobial
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkq429

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.
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.
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.