title: A non-nephrotoxic gentamicin congener that retains antimicrobial efficacy.
abstract: Aminoglycoside antibiotics, although of major clinical importance in the treatment of serious Gram- negative infections and a potential therapeutic agent in the amelioration of diseases that are characterized by premature stop mutations, are associated with a high incidence of acute renal failure. With the use of HPLC techniques, the four components (congeners) of gentamicin, the most commonly used aminoglycoside, were isolated and characterized. Described here is a congener with minimal cytotoxicity in cell culture and animal studies that retained normal bactericidal properties in both Bacillus subtilis and a multidrug-resistant form of Klebsiella pneumoniae. Furthermore, in animal studies, this congener failed to induce the functional and pathologic changes that are characteristic of gentamicin nephrotoxicity that is seen with the native compound. Finally, internalization of this non-nephrotoxic component was unaltered, but the subcellular distribution was different from native gentamicin or the other three cytotoxic congeners. These studies have identified a component of the native gentamicin congener mixture that retains its bactericidal properties with minimal or no apparent nephrotoxicity.
authors.affiliation: Department of Medicine, Nephrology Division, Indiana University School of Medicine, 950 W. Walnut Street, R2-202C, Indianapolis, IN 46202, USA.
authors.forename: Ruben M
authors.initials: RM
authors.lastname: Sandoval
authors.forename: James P
authors.initials: JP
authors.lastname: Reilly
authors.forename: William
authors.initials: W
authors.lastname: Running
authors.forename: Silvia B
authors.initials: SB
authors.lastname: Campos
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Santos
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Phillips
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Molitoris
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D019084:Fluorescent Antibody Technique, Indirect; D005839:Gentamicins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D018374:LLC-PK1 Cells; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins