Protegrin-1 enhances bacterial killing in thermally injured skin.
OBJECTIVE
Septic complications and the emergence of drug-resistant microbes represent serious risks to patients. Recently, naturally occurring peptides have been discovered that possess potent and broad-spectrum antimicrobial activity. Protegrin-1 is particularly attractive for clinical use in human wounds because, unlike defensins, protegrin-1 retains broad antimicrobial and antifungal activity at physiologic salt concentration and in the presence of serum. The objective of this study was to examine the efficacy of protegrin-1 in killing multiple drug-resistant microbes isolated from human burn patients.


METHODS
For thein vitroexperiment, bilayer radial diffusion was performed comparing standard antibiotics with protegrin-1 on multiple-drug-resistant microbial organisms isolated from infected burn wounds. In vivo, rats received a 20% total body surface area partial-thickness burn by immersion in 60 degrees C water for 20 secs followed by wound seeding with 106 colony forming units of Silvadene-resistant Pseudomonas aeruginosa.


METHODS
University of Michigan research laboratory.


METHODS
Adult, male Sprague-Dawley rats.


METHODS
Rats were randomized into three groups: those receiving synthetic protegrin-1, acetic acid (carrier), or gentamicin (positive control). Protegrin-1 was administered by topical application or intradermal injection. Wound tissues were harvested aseptically at different time points for quantitative bacterial counts.


RESULTS
In vivo and in vitro experiments revealed rapid and significant decreases in bacterial counts for protegrin-1-treated groups compared with controls.


CONCLUSIONS
This study shows that protegrin-1 potentially may be used as an alternative or adjunct therapy to standard agents used to treat wound infections.
Steinstraesser
L
L
Departments of Surgery, University of Michigan, Ann Arbor, MI, USA.
Klein
R D
RD
Aminlari
A
A
Fan
M H
MH
Khilanani
V
V
Remick
D G
DG
Su
G L
GL
Wang
S C
SC
D000287:Administration, Topical; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides; D002056:Burns / Q000473:pathology / Q000628:therapy*; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D006801:Humans; D066298:In Vitro Techniques; D007271:Injections, Intradermal; D008297:Male; D011506:Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014946:Wound Infection / Q000517:prevention & control*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D011506:Proteins; C094880:protegrin-1