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Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections

Authors Draughn GL, Allen CL, Routh PA, Stone MR, Kirker KR, Boegli L, Schuchman RM, Linder KE, Baynes RE, James G, Melander C, Pollard A, Cavanagh J

Received 3 May 2016

Accepted for publication 6 July 2016

Published 11 January 2017 Volume 2017:11 Pages 153—162

DOI https://doi.org/10.2147/DDDT.S111865

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Palas Chanda

Peer reviewer comments 3

Editor who approved publication: Dr James Janetka

G Logan Draughn,1 C Leigh Allen,1 Patricia A Routh,2 Maria R Stone,2 Kelly R Kirker,3 Laura Boegli,3 Ryan M Schuchman,1 Keith E Linder,2 Ronald E Baynes,2 Garth James,3 Christian Melander,4 Angela Pollard,5 John Cavanagh1

1Department of Molecular and Structural Biochemistry, 2Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; 3Center for Biofilm Engineering, Montana State University, Bozeman, MT, USA; 4Department of Chemistry, North Carolina State University, Raleigh, NC, USA; 5Agile Sciences Inc., Raleigh, NC, USA

Abstract: 2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.

Keywords: transdermal absorption, antimicrobial activity, skin irritation, synergism, oroidin derivative, drip-flow reactor, ESKAPE pathogens

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