Abstract | PURPOSE: METHODS: Experiments were performed with three clinical ocular isolates--Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis--in three experimental settings: (1) in vitro in a controlled system of 10 mM sodium phosphate buffer, (2) in vitro in modified chondroitin sulfate-based corneal preservation media ( Optisol), and (3) in an in vivo animal model (rabbit) simulating bacterial keratitis. In all cases, outcomes were measured by quantitative microbiological techniques. RESULTS: The candidate peptides (CCI A, B, and C and COL-1) produced a total reduction of the test pathogens in phosphate buffered saline. In modified Optisol, the peptides were effective against S epidermidis at all temperatures, demonstrated augmented activity at 23 degrees C against the gram-positive organisms, but were ineffective against P aeruginosa. The addition of EDTA to the medium augmented the killing of P aeruginosa but made no difference in the reduction of gram-positive organisms. In an in vivo rabbit model of Pseudomonas keratitis, COL-1 demonstrated neither clinical nor microbicidal efficacy and appeared to have a very narrow dosage range, outside of which it appeared to be toxic to the ocular surface. CONCLUSION: Our data indicate that the antimicrobial peptides we tested were effective in vitro but not in vivo. In an age of increasing antibiotic resistance, antimicrobial peptides, developed over millions of years as innate defense mechanisms by plants and animals, may have significant potential for development as topical agents for the management of severe bacterial keratitis. However, modifications of the peptides, the drug delivery systems, or both, will be necessary for effective clinical application.
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Authors | Mark J Mannis |
Journal | Transactions of the American Ophthalmological Society
(Trans Am Ophthalmol Soc)
Vol. 100
Pg. 243-71
( 2002)
ISSN: 0065-9533 [Print] United States |
PMID | 12545697
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Complex Mixtures
- Culture Media, Serum-Free
- Dextrans
- Gentamicins
- Peptide Fragments
- Chondroitin Sulfates
- Optisol
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Topics |
- Animals
- Anti-Bacterial Agents
(chemistry, pharmacology, therapeutic use)
- Chondroitin Sulfates
- Complex Mixtures
- Cornea
(drug effects, microbiology)
- Culture Media, Serum-Free
- Dextrans
- Eye Infections, Bacterial
(drug therapy, microbiology)
- Gentamicins
- Humans
- Keratitis
(drug therapy, microbiology)
- Organ Preservation
- Peptide Fragments
(chemical synthesis, chemistry)
- Pseudomonas Infections
(drug therapy, microbiology)
- Pseudomonas aeruginosa
(drug effects, isolation & purification)
- Rabbits
- Sheep
- Staphylococcal Infections
(drug therapy, microbiology)
- Staphylococcus aureus
(drug effects, isolation & purification)
- Staphylococcus epidermidis
(drug effects, isolation & purification)
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