External Eye Diseases
The In Vitro and In Vivo Antibacterial Evaluation of Brilacidin
Regis P. Kowalski1, Eric Romanowski1, Kathleen Yates1, Robert Shanks1, Francis Mah2
1Ophthalmology, University of Pittsburgh, USA
2Ophthalmology, Scripps Health, USA
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 efficacy of BRI as an ocular anti-infective.
Methods: In vitro: MICs were determined for ocular isolates (n = 25/ bacteria) of Ciprofloxacin-Susceptible-Staphylococcus aureus-(CSSA), Ciprofloxacin-Resistant-Staphylococcus aureus- (CRSA), CS-Staphylococcus- epidermidis- (CSSE), CR-Staphylococcus- epidermidis- (CRSE), Streptococcus- pneumonia-(SP), Streptococcus-viridans- (SV), Moraxella- (MS), Haemophilus-influenzae- (HI), Pseudomonas-aeruginosa- (PA), and Serratia- marcescens-(SM). In vivo: In 24 NZW rabbits, the left cornea was abraded and the right remained intact. The corneas were infected with 1000 CFU of MRSA. Four hrs passed. Topical drops were administered (every 15’ for 5 hrs) to 4 respective groups: A) BRI 0.5%,
Vancomycin (VAN) 5%, C) saline (SAL), and D) no treatment (baseline CFU). One hr after treatment the corneas were harvested for CFU. Results: In vitro: Data (μg/ml) is expressed as MIC50, MIC90, and MIC Range. 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-
; SM(8, 32, 0.25-32). In vivo: For abraded corneas, VAN=BRISal for reductions in MRSA CFU. BRI demonstrated a 99.9% reduction compared to baseline CFU. For intact corneas, VANBRI SAL. BRI=baseline counts suggesting the corneal epithelium acts as a barrier for penetration. 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.
The In Vitro and In Vivo Antibacterial Evaluation of Brilacidin
Regis P. Kowalski1, Eric Romanowski1, Kathleen Yates1, Robert Shanks1, Francis Mah2
1Ophthalmology, University of Pittsburgh, USA
2Ophthalmology, Scripps Health, USA
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 efficacy of BRI as an ocular anti-infective.
Methods: In vitro: MICs were determined for ocular isolates (n = 25/ bacteria) of Ciprofloxacin-Susceptible-Staphylococcus aureus-(CSSA), Ciprofloxacin-Resistant-Staphylococcus aureus- (CRSA), CS-Staphylococcus- epidermidis- (CSSE), CR-Staphylococcus- epidermidis- (CRSE), Streptococcus- pneumonia-(SP), Streptococcus-viridans- (SV), Moraxella- (MS), Haemophilus-influenzae- (HI), Pseudomonas-aeruginosa- (PA), and Serratia- marcescens-(SM). In vivo: In 24 NZW rabbits, the left cornea was abraded and the right remained intact. The corneas were infected with 1000 CFU of MRSA. Four hrs passed. Topical drops were administered (every 15’ for 5 hrs) to 4 respective groups: A) BRI 0.5%,
Vancomycin (VAN) 5%, C) saline (SAL), and D) no treatment (baseline CFU). One hr after treatment the corneas were harvested for CFU. Results: In vitro: Data (μg/ml) is expressed as MIC50, MIC90, and MIC Range. 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-; SM(8, 32, 0.25-32). In vivo: For abraded corneas, VAN=BRISal for reductions in MRSA CFU. BRI demonstrated a 99.9% reduction compared to baseline CFU. For intact corneas, VANBRI SAL. BRI=baseline counts suggesting the corneal epithelium acts as a barrier for penetration. 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.