Intramuscularly administered peptide A3-APO is effective against carbapenem-resistant Acinetobacter baumannii in mouse models of systemic infections.
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.
Ostorhazi
Eszter
E
Department of Dermatology, Microbiology Laboratory, Venereology and Dermato-Oncology, Semmelweis University, Budapest, Hungary.
Rozgonyi
Ferenc
F
Szabo
Dora
D
Binas
Annegret
A
Cassone
Marco
M
Wade
John D
JD
Nolte
Oliver
O
Bethel
Christopher R
CR
Bonomo
Robert A
RA
Otvos
Laszlo
L
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*
C539766:A3-APO peptide; D000900:Anti-Bacterial Agents; D015780:Carbapenems; D010455:Peptides