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

Gerald A. Denys, Parveen Grover, Peter O'Hanley, Jackson T. Stephens

Research output: Contribution to journalArticle

6 Scopus citations

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 MIC90 values of 0.03, 0.5 and 0.5 mg pMPO/L for staphylococci (n=140), streptococci (n=95) and enterococci (n=55), respectively. MIC90 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.

Original languageEnglish (US)
Article numberdkq429
Pages (from-to)335-342
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume66
Issue number2
DOIs
StatePublished - Feb 1 2011

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Keywords

  • Singlet oxygen
  • Surgical site infections
  • Therapeutic enzyme system
  • Topical antimicrobial

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

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