title: Novel antiseptic compound OPB-2045G shows potent bactericidal activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus both in vitro and in vivo: a pilot study in animals.
abstract: There is a need for new compounds to effectively treat methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). The novel monobiguanide compound 1-(3,4-dichlorobenzyl)-5-octylbiguanide gluconate (OPB-2045G) has potential bactericidal activity. We sought to elucidate the potency of OPB-2045G bactericidal activity against MRSA and VRE compared to those of chlorhexidine digluconate (CHG) and povidone iodine (PVP-I). In vitro bactericidal activity was analysed using minimum bactericidal concentration (MBC) as the index. The in vivo bactericidal efficacy of OPB-2045G was examined by determining MRSA and VRE contamination of the normal dorsal skin of mice following removal of hair. After a 3 min treatment period, the MBC of OPB-2045G was lower than that of CHG and PVP-I against standard strains and clinical isolates. Additionally, in our in vivo mouse model, the in vivo bactericidal activity of 1.5 % OPB-2045G (a clinically relevant dose) was higher than that of 0.5 % CHG and equivalent to that of 10 % PVP-I against MRSA. Similarly, the in vivo bactericidal activity of OPB-2045G was higher than that of 0.5 % CHG and 10 % PVP-I against VRE. OPB-2045G showed more potent bactericidal activity against MRSA and VRE both in vitro and in vivo compared to CHG and PVP-I, indicating that OPB-2045G may provide better protection against health care-associated infections caused by these pathogens.
authors.affiliation: Naruto Research Institute, Research and Development Centre, Otsuka Pharmaceutical Factory Inc., Tokushima, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Naruto Research Institute, Research and Development Centre, Otsuka Pharmaceutical Factory Inc., Tokushima, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Hagi
authors.affiliation: Naruto Research Institute, Research and Development Centre, Otsuka Pharmaceutical Factory Inc., Tokushima, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nii
authors.affiliation: Naruto Research Institute, Research and Development Centre, Otsuka Pharmaceutical Factory Inc., Tokushima, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Tsubotani
authors.affiliation: Naruto Research Institute, Research and Development Centre, Otsuka Pharmaceutical Factory Inc., Tokushima, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Nakata
authors.affiliation: Naruto Research Institute, Research and Development Centre, Otsuka Pharmaceutical Factory Inc., Tokushima, Japan.
authors.forename: Koushi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology* / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000517:prevention & control; D002710:Chlorhexidine / Q000627:therapeutic use; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008813:Mice, Inbred ICR; D050296:Microbial Viability / Q000187:drug effects; D010865:Pilot Projects; D011206:Povidone-Iodine / Q000627:therapeutic use; D012867:Skin / Q000382:microbiology; D016896:Treatment Outcome; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects*
chemical_list: D000891:Anti-Infective Agents, Local; D011206:Povidone-Iodine; D002710:Chlorhexidine