title: A single dose of epidermicin NI01 is sufficient to eradicate MRSA from the nares of cotton rats.
abstract: To investigate the efficacy of a potent novel antimicrobial protein of mass 6 kDa, epidermicin NI01, for eradicating the nasal burden of MRSA in a cotton rat ( Sigmodon hispidus ) model.
  
  
  
  MRSA strain ATCC 43300 was used to establish a robust colonization of cotton rat nares. This model was used to evaluate the efficacy of topical 0.04% and 0.2% epidermicin NI01, administered twice daily for 3 days consecutively, and topical 0.8% epidermicin NI01 administered once, for reducing nasal MRSA burden. Control groups remained untreated or were administered vehicle only (0.5% hydroxypropylmethylcellulose) or 2% mupirocin twice daily for 3 days. The experiment was terminated at day 5 and MRSA quantitative counts were determined. Tissues recovered from animals treated with 0.2% epidermicin twice daily for 3 days were examined for histological changes.
  
  
  
  Mupirocin treatment resulted in a reduction in burden of log 10 (log R) of 2.59 cfu/nares compared with vehicle ( P  < 0.0001). Epidermicin NI01 administered once at 0.8% showed excellent efficacy, resulting in a log R of 2.10 cfu/nares ( P  = 0.0004), which was equivalent to mupirocin. Epidermicin NI01 administered at 0.2% or 0.04% twice daily for 3 days did not have a significant impact on the tissue burden recovered from the nares. Mild to marked histological abnormalities were noted, but these were determined to be reversible.
  
  
  
  A single dose of topical epidermicin NI01 was as effective as mupirocin administered twice daily for 3 days in eradication of MRSA from the nares of cotton rats. This justifies further development of epidermicin for this indication.
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: Samantha
authors.initials: S
authors.lastname: Halliwell
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Evotec (UK) Ltd, Manchester Science Park, Manchester, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Warn
authors.affiliation: Evotec (UK) Ltd, Manchester Science Park, Manchester, UK.
authors.forename: Abdul
authors.initials: A
authors.lastname: Sattar
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Derrick
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|School of Biomedical & Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK.
authors.forename: Mathew
authors.initials: M
authors.lastname: Upton
mesh_terms: D000287:Administration, Topical; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000627:therapeutic use; D058491:Bacterial Load / Q000187:drug effects; D001430:Bacteriocins / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D016712:Mupirocin / Q000627:therapeutic use; D009666:Nose / Q000187:drug effects / Q000382:microbiology*; D051381:Rats; D016205:Sigmodontinae; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D023181:Antimicrobial Cationic Peptides; D001430:Bacteriocins; C574453:epidermicin NI01, Staphylococcus epidermidis; D016712:Mupirocin