Therapeutic Efficacy of Novel Antimicrobial Peptide AA139-Nanomedicines in a Multidrug-Resistant Klebsiella pneumoniae Pneumonia-Septicemia Model in Rats
Hessel van der Weide, Unai Cossío, Raquel Gracia, Yvonne M. te Welscher, Marian T. ten Kate, Aart van der Meijden, Marco Marradi, Jeffrey A. S. Ritsema, Denise M. C. Vermeulen-de Jongh, Gert Storm, Wil H. F. Goessens, Iraida Loinaz, Cornelus F. van Nostrum, Jordi Llop, John P. Hays, Irma A. J. M. Bakker‐Woudenberg
Abstract
antimicrobial activities (similar to free AA139). In uninfected rats, they exhibited longer residence times in the lungs than free AA139 (∼20% longer for AA139-PNP and ∼80% longer for AA139-MCL), as well as reduced toxicity, enabling a higher limiting dose. In rats with pneumonia-septicemia, both AA139-nanomedicines showed significantly improved therapeutic efficacy in terms of an extended rat survival time, although survival of all rats was not achieved. These results demonstrate potential advantages that can be achieved using AMP-nanomedicines. AA139-PNP and AA139-MCL may be promising novel therapeutic agents for the treatment of patients suffering from multidrug-resistant Gram-negative pneumonia-septicemia.