Abstract
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...Continue Reading
References
May 1, 1986·Antimicrobial Agents and Chemotherapy·D J SwansonJ J Schentag
Nov 23, 2000·Biochemistry·L OtvosM Blaszczyk-Thurin
Mar 22, 2001·Biochemistry·G KragolL Otvos
Aug 5, 2005·Journal of Medicinal Chemistry·Laszlo OtvosRalf Hoffmann
Apr 17, 2008·Protein Science : a Publication of the Protein Society·Paul Bart NotoLaszlo Otvos
Aug 30, 2008·Peptides·Marco CassoneLaszlo Otvos
Sep 15, 2009·Current Medicinal Chemistry·F RozgonyiL Otvos
Dec 25, 2009·International Journal of Antimicrobial Agents·Dora SzaboLaszlo Otvos
Jun 22, 2010·Biopolymers·Eszter OstorhaziLaszlo Otvos
Sep 3, 2010·The Journal of Antimicrobial Chemotherapy·Eszter OstorhaziLaszlo Otvos
Mar 1, 2011·International Journal of Antimicrobial Agents·Eszter OstorhaziLaszlo Otvos
Jan 19, 2012·PloS One·Guanpingshen LuoBrad Spellberg
Mar 6, 2012·Mayo Clinic Proceedings·Stephen G Jenkins, Audrey N Schuetz
Jun 26, 2012·The Journal of Antimicrobial Chemotherapy·Daniel KnappeUwe Müller
Apr 9, 2013·Journal of Molecular Biology·Michael ZahnNorbert Sträter
Oct 1, 2013·International Journal of Antimicrobial Agents·Eszter OstorhaziLaszlo Otvos
Aug 12, 2014·Biochimica Et Biophysica Acta·Jéssica M NascimentoCésar A S Andrade
Nov 8, 2014·The Journal of Infectious Diseases·Kevin W BruhnBrad Spellberg
Apr 24, 2015·PloS One·Federica ChiapporiIvan Merelli
May 15, 2015·Biopolymers·Daniel KnappeRalf Hoffmann
May 26, 2015·Clinics in Laboratory Medicine·Romney M Humphries, Audrey N Schuetz
Sep 1, 2015·Amino Acids·Istvan SebeLaszlo Otvos
Sep 20, 2015·Chemistry & Biology·Wenyi LiJohn D Wade
Mar 18, 2016·Virulence·Murat Akova
Aug 20, 2016·Acta Microbiologica Et Immunologica Hungarica·Laszlo Otvos
Feb 6, 2017·Frontiers in Chemistry·Wenyi LiJohn D Wade
Apr 13, 2018·Frontiers in Pharmacology·Anja PfalzgraffGünther Weindl
Aug 30, 2018·Frontiers in Chemistry·Laszlo OtvosCarl N Kraus
Sep 7, 2018·Frontiers in Chemistry·Eszter OstorhaziLaszlo Otvos