Antibacterial activity of apramycin at acidic pH warrants wide therapeutic window in the treatment of complicated urinary tract infections and acute pyelonephritis

The clinical-stage drug candidate EBL-1003 (apramycin) represents a distinct new subclass of aminoglycoside antibiotics for the treatment of drug-resistant infections. It has demonstrated best-in-class coverage of resistant isolates, and preclinical efficacy in lung infection models. However, precli...

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Bibliographic Details
Published in:	EBioMedicine Vol. 73; p. 103652
Main Authors:	Becker, Katja, Cao, Sha, Nilsson, Anna, Erlandsson, Maria, Hotop, Sven-Kevin, Kuka, Janis, Hansen, Jon, Haldimann, Klara, Grinberga, Solveiga, Berruga-Fernández, Talia, Huseby, Douglas L., Shariatgorji, Reza, Lindmark, Evelina, Platzack, Björn, Böttger, Erik C., Crich, David, Friberg, Lena E., Vingsbo Lundberg, Carina, Hughes, Diarmaid, Brönstrup, Mark, Andrén, Per E., Liepinsh, Edgars, Hobbie, Sven N.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01.11.2021 Elsevier
Subjects:	acute pyelonephritis Advanced Basic Science amikacin animal model animal tissue Animals Anti-bacterial agents Anti-Bacterial Agents - pharmacology Anti-Bacterial Agents - therapeutic use antibacterial activity antibiotic resistance antibiotic sensitivity apramycin Bacterial Infections - drug therapy Bacterial Infections - microbiology delta pH Disease Models, Animal Dose-Response Relationship, Drug drug efficacy Drug Resistance, Multiple, Bacterial - drug effects drug safety drug uptake efficacy Escherichia coli female gentamicin high performance liquid chromatography Humans Hydrogen-Ion Concentration in vitro study in vivo study Internal Medicine kanamycin kidney function Klebsiella pneumoniae liquid chromatography-mass spectrometry male mass spectrometry Mice Microbial Sensitivity Tests minimum inhibitory concentration mouse multidrug resistance Nebramycin - analogs & derivatives Nebramycin - pharmacology Nebramycin - therapeutic use nephrotoxicity nonhuman permeability pharmacokinetics proton-motive force Pseudomonas aeruginosa Pyelonephritis - drug therapy Pyelonephritis - etiology rat Rats Research paper Treatment Outcome urinary tract urinary tract infection Urinary Tract Infections - drug therapy Urinary Tract Infections - etiology urine pH uropathogen proton-motive force nephrotoxicity Anti-bacterial agents delta pH permeability urinary tract drug uptake efficacy
ISSN:	2352-3964, 2352-3964
Online Access:	Get full text
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