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Open AccessArticle

Efficacy of ARV-1502, a Proline-Rich Antimicrobial Peptide, in a Murine Model of Bacteremia Caused by Multi-Drug Resistant (MDR) Acinetobacter baumannii

1
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA
2
Geffen Sch. of Med. at UCLA, Los Angeles, CA 90095, USA
3
Arrevus, Inc. Research Triangle Park, NC 27612, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Jean-Marc Sabatier
Molecules 2019, 24(15), 2820; https://doi.org/10.3390/molecules24152820
Received: 1 July 2019 / Revised: 19 July 2019 / Accepted: 30 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue Bioactive Peptides—From Therapy to Nutrition)
Acinetobacter baumannii bacteremia represents a serious and increasing clinical problem due to the high mortality and treatment failures because of high rates of antibiotic resistance. Any additional new therapies for A. baumannii bacteremia would address a growing unmet medical need. ARV-1502 (designated as Chex1-Arg20 or A3-APO monomer in prior publications) is a designer proline-rich antimicrobial peptide chaperone protein inhibitor derived from insects and has demonstrated potent activity against multi-drug resistant (MDR) Gram-negative bacteria. In the current studies, we investigated the therapeutic efficacy of ARV-1502 administered intravenously (iv) alone and in combination with imipenem/cilastatin (IPM/CIL) in a mouse bacteremia model due to a MDR clinical A. baumannii strain, HUMC1. All ARV-1502 regimens (1.25, 2.5 and 5.0 mg/kg) significantly reduced bacterial density in the target tissues in a dose-dependent manner, as compared to the untreated control and IPM/CIL monotherapy (40 mg/kg) groups in the model. In addition, ARV-1502 treatment, even at the lowest dose, significantly improved survival vs. the control and IPM alone groups. As expected, IMP/CIL monotherapy had no therapeutic efficacy in the model, since the HUMC1 strain was resistant to IMP in vitro. However, the combination of ARV-1502 and IPM/CIL significantly enhanced the efficacy of ARV-1502, except the lowest dose of ARV-1502. The superior efficacy of ARV-1502 in the bacteremia model caused by MDR A. baumannii provides further support for studying this compound in severe infections caused by other MDR Gram-positive and -negative pathogens. View Full-Text
Keywords: multi-drug resistant Acinetobacter baumannii; antimicrobial peptide; bacteremia; host defense peptide multi-drug resistant Acinetobacter baumannii; antimicrobial peptide; bacteremia; host defense peptide
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Xiong, Y.Q.; Li, L.; Zhou, Y.; Kraus, C.N. Efficacy of ARV-1502, a Proline-Rich Antimicrobial Peptide, in a Murine Model of Bacteremia Caused by Multi-Drug Resistant (MDR) Acinetobacter baumannii. Molecules 2019, 24, 2820.

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