In vitro antibacterial properties of pexiganan, an analog of magainin

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 (MIC90) was 32 mu g/ml or less for Staphylococcus sop., Streptococcus spp., Enterococcus faecium, Corynebacterium spp,, Pseudomonas spp,, Acinetobacter spp,, Stenotrophomonas spp,, certain species of the family Enterobacteriaceae, Bacteroids 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 mu g of pexiganan per mi, 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.