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Intramuscularly administered peptide A3-APO is effective against carbapenem-resistant Acinetobacter baumannii in
Eszter Ostorhazi1, Ferenc Rozgonyi, Dora Szabo
1Department of Dermatology, Microbiology Laboratory, Venereology and Dermato-Oncology, Semmelweis University, Budapest, Hungary.
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.
Insights
Peptide A3-APO effectively combats carbapenem-resistant Acinetobacter baumannii systemic infections in mice, significantly increasing survival rates and reducing bacterial load. This peptide shows promise as a therapeutic agent against multidrug-resistant bacterial infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Antibacterial peptides often have limited therapeutic efficacy in vivo.
- Peptide A3-APO demonstrated high potency against Escherichia coli bacteremia.
- Systemic infections caused by multidrug-resistant organisms (MDROs) pose a significant therapeutic challenge.
Purpose of the Study:
- To evaluate the efficacy of peptide A3-APO against systemic infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in mouse models.
- To assess the therapeutic index and safety profile of A3-APO in treating CRAB infections.
Main Methods:
- Mouse models of CRAB infection were established.
- Peptide A3-APO was administered intravenously (2.5 mg/kg) or intramuscularly (5 mg/kg) multiple times.
- Bacterial counts and survival rates were compared between treated and untreated groups, as well as with imipenem treatment.
- Toxicological effects of A3-APO were assessed at a high intramuscular dose (60 mg/kg).
Main Results:
- Intravenous or intramuscular administration of A3-APO significantly reduced CRAB bacterial counts by at least two log10 units.
- A3-APO treatment led to increased survival rates compared to untreated controls and imipenem treatment.
- Unlike other administration routes, intramuscular A3-APO showed no toxic effects at a dose of 60 mg/kg.
Conclusions:
- Peptide A3-APO demonstrates significant efficacy in treating systemic CRAB infections in mice.
- A3-APO offers a promising therapeutic option against MDROs, with a favorable safety profile, particularly via intramuscular administration.
- Further investigation into A3-APO as a treatment for infections caused by carbapenem-resistant pathogens is warranted.
