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

Abstract

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.