Affiliation:
1. Magainin Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania 194621;
2. MRL Pharmaceutical Services, Franklin, Tennessee 370642; and
3. Wadsworth Anaerobe Laboratories, Los Angeles, California 900733
Abstract
ABSTRACT
Pexiganan, a 22-amino-acid antimicrobial peptide, is an analog of the magainin peptides isolated from the skin of the African clawed frog. Pexiganan exhibited in vitro broad-spectrum antibacterial activity when it was tested against 3,109 clinical isolates of gram-positive and gram-negative, anaerobic and aerobic bacteria. The pexiganan MIC at which 90% of isolates are inhibited (MIC
90
) was 32 μg/ml or less for
Staphylococcus
spp.,
Streptococcus
spp.,
Enterococcus faecium
,
Corynebacterium
spp.,
Pseudomonas
spp.,
Acinetobacter
spp.,
Stenotrophomonas
spp., certain species of the family
Enterobacteriaceae
,
Bacteroides
spp.,
Peptostreptococcus
spp., and
Propionibacterium
spp. Comparison of the MICs and minimum bactericidal concentrations (MBCs) of pexiganan for 143 isolates representing 32 species demonstrated that for 92% of the isolates tested, MBCs were the same or within 1 twofold difference of the MICs, consistent with a bactericidal mechanism of action. Killing curve analysis showed that pexiganan killed
Pseudomonas aeruginosa
rapidly, with 10
6
organisms/ml eliminated within 20 min of treatment with 16 μg of pexiganan per ml. No evidence of cross-resistance to a number of other antibiotic classes was observed, as determined by the equivalence of the MIC
50
s and the MIC
90
s of pexiganan for strains resistant to oxacillin, cefazolin, cefoxitin, imipenem, ofloxacin, ciprofloxacin, gentamicin, and clindamicin versus those for strains susceptible to these antimicrobial agents. Attempts to generate resistance in several bacterial species through repeated passage with subinhibitory concentrations of pexiganan were unsuccessful. In conclusion, pexiganan exhibits properties in vitro which make it an attractive candidate for development as a topical antimicrobial agent.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
315 articles.
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