title: In vivo activity of optimized apidaecin and oncocin peptides against a multiresistant, KPC-producing Klebsiella pneumoniae strain.
abstract: The peptides Api88 and Onc72 are highly efficient to treat Escherichia coli bacteremia in mice. Here we extended the animal studies to a systemic murine infection model using a multidrug-resistant carbapenemase-producing Klebsiella pneumoniae clinical isolate. When administered intraperitoneally three times at 2.5, 5 and 10 mg/kg bodyweight to CD-1 mice infected with a KPC-producing K. pneumoniae strain, both Api88 and Onc72 reduced the bacterial counts by at least 5 log₁₀ units, indicating that both peptides are active in vivo. Both peptide treatments increased significantly the survival rates and average survival times compared to untreated animals for all doses except for the highest dose of Onc72. This dose reduced the bacterial counts so fast that it most likely induced a sudden release of large amounts of toxic materials from the killed bacteria reducing the survival time even below that of untreated mice. In conclusion, both peptides were efficient in the lethal murine K. pneumoniae infection model, but the treatment protocol (i.e. dose and time points) has to be further optimized based on future pharmacokinetic studies.
authors.forename: Eszter
authors.initials: E
authors.lastname: Ostorhazi
authors.forename: Éva
authors.initials: É
authors.lastname: Nemes-Nikodem
authors.forename: Daniel
authors.initials: D
authors.lastname: Knappe
authors.affiliation: Semmelweis University, Department of Dermatology, Venerology and Dermatooncology, Mária street 41, Budapest, 1085, Hungary. ostorhazi.eszter@med.semmelweis-univ.hu.
authors.forename: Ralf
authors.initials: R
authors.lastname: Hoffmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; C551620:oncocin; C061361:apidaecin; D001618:beta-Lactamases; C063912:carbapenemase