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The In Vitro and In Vivo Antibacterial Evaluation of Brilacidin
Posterboard #: C0149
Abstract Number: 264 - C0149
Author Block: Regis P. Kowalski1 , Eric G. Romanowski1 , Robert M. Shanks1 , Kathleen Yates1 , Francis S. Mah1,2
1 Ophthalmology, The Charles T. Campbell Lab - UPMC, Pittsburgh, Pennsylvania, United States; 1 Ophthalmology, The Charles T. Campbell Lab - UPMC, Pittsburgh, Pennsylvania, United States; 1 Ophthalmology, The Charles T. Campbell Lab - UPMC, Pittsburgh, Pennsylvania, United States; 1 Ophthalmology, The Charles T. Campbell Lab - UPMC, Pittsburgh, Pennsylvania, United States; 1 Ophthalmology, The Charles T. Campbell Lab - UPMC, Pittsburgh, Pennsylvania, United States; 2 Ophthalmology, Scripps-Health, San Diego, California, United States
Disclosure Block:Regis P. Kowalski, PolyMedix (Code F (Financial Support)), PolyMedix (Code F (Financial Support)), PolyMedix (Code F (Financial Support)); Eric G. Romanowski, PolyMedix (Code F (Financial Support)), PolyMedix (Code F (Financial Support)), PolyMedix (Code F (Financial Support)); Robert M. Shanks, None; Kathleen Yates, None; Francis S. Mah, PolyMedix (Code F (Financial Support)), PolyMedix (Code F (Financial Support)), PolyMedix (Code F (Financial Support))
Purpose:Brilacidin (BRI) (PMX30063) is the first anti-infective in a new class of defensin mimetics. The goals of the study were to evaluate the in vitro and in vivo efficacy of BRI as an ocular anti-infective.
Methods:In vitro: MICs using broth dilution were determined for clinical ocular isolates (n = 25 per bacteria) of Ciprofloxacin Susceptible (CS) Staphylococcus aureus (CSSA), Ciprofloxacin Resistant (CR) Staphylococcus aureus (CRSA), CS Staphylococcus epidermidis (CSSE), CR Staphylococcus epidermidis (CRSE), Streptococcus pneumoniae (SP), Streptococcus viridans group (SV), Moraxella Species (MS), Haemophilus influenzae (HI), Pseudomonas aeruginosa (PA), and Serratia marcescens (SM). In vivo: In 24 NZW rabbits, corneal epithelial defects were created OS (abraded corneas), while the epithelium OD remained intact (intact corneas) to determine the effect of drug penetration. The corneas were intrastromally injected with 1000 CFU of MRSA. Rabbits were separated into 4 groups (n=6): A) BRI 0.5%, B) Vancomycin (VAN) 5%, C) saline (SAL), and D) no treatment (baseline CFU). Four hrs after MRSA challenge, topical treatment of one drop every 15’ for 5 hrs was initiated. One hr after treatment the corneas were harvested for CFU. The data were non-parametrically analyzed.
Results:In vitro: Data is expressed as MIC50, MIC90, and Range of MICs in µg/ml. CSSA (0.25, 0.25, 0.125-0.5); CRSA (0.25, 0.5, 0.125-1.0); CSSE (0.125, 0.25, 0.03125-0.25); CRSE (0.125, 0.25, 0.03125-0.25); SP (1, 1, 0.5-128); MS (4, 64, 0.5-128); HI (8, 8, 2-32); PA (4, 4, 0.5-8); SM (8, 32, 0.25-32). In vivo: For abraded corneas, VAN and BRI produced similar reductions in MRSA CFU, and were less than saline (P<0.05, K-W). However, only BRI demonstrated a 99.9% reduction compared to baseline CFU. For intact corneas, VAN significantly reduced CFU compared with BRI which demonstrated a slight but significant decrease vs. SAL (P<0.05, K-W). BRI reduced CFU in abraded corneas significantly more than intact corneas (P<0.05, M-W) suggesting the corneal epithelium acts as a barrier for penetration. There was no difference in CFU in abraded and intact corneas with VAN (P>0.05, M-W) suggesting high penetration through the corneal epithelium.
Conclusions:BRI demonstrated broad spectrum in vitro activity against ocular pathogens. BRI was equally efficacious as VAN in a MRSA keratitis model only when the corneal epithelium was removed.
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