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.
Keywords: Antibacterial peptides, Api88, Klebsiella pneumoniae carbapenemase (KPC), murine infection model, Onc72.
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