title: In vitro spectrum of pexiganan activity when tested against pathogens from diabetic foot infections and with selected resistance mechanisms.
abstract: Pexiganan, a 22-amino-acid synthetic cationic peptide, is currently in phase 3 clinical trials as a topical antimicrobial agent for the treatment of mild infections associated with diabetic foot ulcers. Bacterial isolates from the 2013 SENTRY Antimicrobial Surveillance Program designated as pathogens from diabetic foot infections (DFI) and Gram-negative and -positive pathogens from various infection types that harbored selected resistance mechanisms/phenotypes were tested against pexiganan in reference cation-adjusted Mueller-Hinton broth. The MIC50 and MIC90 against all organisms tested from DFI were 16 and 32 μg/ml, respectively. Escherichia coli, Klebsiella pneumoniae, Citrobacter koseri, Enterobacter cloacae, Acinetobacter species, and Pseudomonas aeruginosa MIC values ranged from 8 to 16 μg/ml. Pexiganan MIC values among Staphylococcus aureus (methicillin-resistant S. aureus [MRSA] and methicillin-susceptible S. aureus [MSSA]), beta-hemolytic streptococci, and Enterococcus faecium ranged from 8 to 32 μg/ml. Pexiganan activity was not adversely affected for members of the family Enterobacteriaceae or P. aeruginosa that produced β-lactamases or resistance mechanisms to other commonly used antimicrobial agents. Decreased susceptibility to vancomycin did not affect pexiganan activity against S. aureus or E. faecium. Enterococcus faecalis appears to be intrinsically less susceptible to pexiganan (MIC, 32 to 256 μg/ml). The "all organism" MIC90 of 32 μg/ml for pexiganan in this study was >250-fold below the pexiganan concentration in the cream/delivery vehicle being developed for topical use.
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA robert-flamm@jmilabs.com.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Rhomberg
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Simpson
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D017719:Diabetic Foot / Q000382:microbiology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C093828:pexiganan