An Independent Evaluation of a Novel Peptide Mimetic, Brilacidin (PMX30063), for Ocular Anti-infective.
OBJECTIVE
Brilacidin (BRI), a novel defensin mimetic, was evaluated as an ocular anti-infective.


METHODS
In vitro: Potency based on MIC90s was compared for 50 Staphylococcus aureus (SA), 50 Staphylococcus epidermidis (SE), and 25 each of Streptococcus pneumonia (SP), Streptococcus viridans (SV), Moraxella (MS), Haemophilus influenzae (HI), Pseudomonas aeruginosa (PA), and Serratia marcescens (SM). In vivo: Using established methods, ocular toxicity was graded with Draize testing. For efficacy testing, both corneas of 24 rabbits were infected with methicillin-resistant S. aureus (MRSA), whereas the corneal epithelium was removed in the left eye. After 4 h, 21 topical drops over 5 h were administered to 4 groups: BRI 0.5%, vancomycin (VAN) 5%, saline, and no treatment. The eyes were clinically graded and the corneas were harvested for colony counts.


RESULTS
In vitro: Both SA and SE had the lowest minimum inhibitory concentrations among the bacterial groups. The MIC90s to BRI for SP, SV, MS, HI, PA, and SM were 4, 32, 256, 32, 16, and 128-fold higher, respectively, than SA and SE. In vivo: Draize testing determined BRI 0.5% to be minimally irritating. For abraded corneas, BRI was not statistically different from VAN for reducing MRSA. BRI was bactericidal. For intact corneas, VAN reduced more CFU than BRI. BRI reduced CFU in abraded corneas more than intact corneas suggesting poor corneal penetration.


CONCLUSIONS
BRI has Gram-positive in vitro activity; topical BRI 0.5% was minimally irritating; and BRI 0.5% was equally efficacious as VAN in a MRSA keratitis model when the corneal epithelium was removed.
The Charles T. Campbell Eye Microbiology Laboratory, Department of Ophthalmology, University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
Regis P
RP
Kowalski
The Charles T. Campbell Eye Microbiology Laboratory, Department of Ophthalmology, University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
Eric G
EG
Romanowski
The Charles T. Campbell Eye Microbiology Laboratory, Department of Ophthalmology, University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
Kathleen A
KA
Yates
The Charles T. Campbell Eye Microbiology Laboratory, Department of Ophthalmology, University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
Francis S
FS
Mah
D060433:Administration, Ophthalmic; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D032701:Biomimetics; D023082:Defensins / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015818:Eye Infections, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D023082:Defensins; D006146:Guanidines; D011743:Pyrimidines; C000611530:brilacidin