A single dose of epidermicin NI01 is sufficient to eradicate MRSA from the nares of cotton rats

J Antimicrob Chemother. 2017 Mar 1;72(3):778-781. doi: 10.1093/jac/dkw457.

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Antimicrobial Cationic Peptides / administration & dosage*
  • Antimicrobial Cationic Peptides / therapeutic use
  • Bacterial Load / drug effects
  • Bacteriocins / administration & dosage*
  • Bacteriocins / therapeutic use
  • Dose-Response Relationship, Drug
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Mupirocin / therapeutic use
  • Nose / drug effects
  • Nose / microbiology*
  • Rats
  • Sigmodontinae
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology

Substances

  • Antimicrobial Cationic Peptides
  • Bacteriocins
  • epidermicin NI01, Staphylococcus epidermidis
  • Mupirocin