title: Intramuscularly administered peptide A3-APO is effective against carbapenem-resistant Acinetobacter baumannii in mouse models of systemic infections.
abstract: Most antibacterial peptides exhibit low therapeutic indices in vivo. Peptide A3-APO was shown to exhibit high potency against Escherichia coli bacteremia when added intraperitoneally. To extend the studies to systemic infections against multidrug-resistant organisms, we studied the efficacy of A3-APO in mouse models of carbapenem-resistant Acinetobacter baumannii infection. When administered either intravenously at 2.5 mg/kg or intramuscularly (im) at 5 mg/kg twice or three times to mice infected with a carbapenem-resistant A. baumannii strain, peptide A3-APO reduced the bacterial counts by at least two log10 units and increased the survival rate compared with untreated animals or mice treated with 40 mg/kg imipenem. Unlike after intraperitoneal or intravenous administration, A3-APO did not show toxic effects at 60 mg/kg dose im.
authors.affiliation: Department of Dermatology, Microbiology Laboratory, Venereology and Dermato-Oncology, Semmelweis University, Budapest, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Ostorhazi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Rozgonyi
authors.forename: Dora
authors.initials: D
authors.lastname: Szabo
authors.forename: Annegret
authors.initials: A
authors.lastname: Binas
authors.forename: Marco
authors.initials: M
authors.lastname: Cassone
authors.forename: John D
authors.initials: JD
authors.lastname: Wade
authors.forename: Oliver
authors.initials: O
authors.lastname: Nolte
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Bethel
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
authors.forename: Laszlo
authors.initials: L
authors.lastname: Otvos
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005260:Female; D051379:Mice; D010455:Peptides / Q000494:pharmacology*
chemical_list: C539766:A3-APO peptide; D000900:Anti-Bacterial Agents; D015780:Carbapenems; D010455:Peptides