A non-nephrotoxic gentamicin congener that retains antimicrobial efficacy

Ruben M. Sandoval, James P. Reilly, William Running, Silvia B. Campos, Joseph R. Santos, Carrie L. Phillips, Bruce A. Molitoris

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2697-2705
Number of pages9
JournalJournal of the American Society of Nephrology
Volume17
Issue number10
DOIs
StatePublished - Oct 1 2006

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Gentamicins
Aminoglycosides
Klebsiella pneumoniae
Bacillus subtilis
Acute Kidney Injury
Cell Culture Techniques
High Pressure Liquid Chromatography
Anti-Bacterial Agents
Mutation
Incidence
Infection
Therapeutics

ASJC Scopus subject areas

  • Nephrology

Cite this

A non-nephrotoxic gentamicin congener that retains antimicrobial efficacy. / Sandoval, Ruben M.; Reilly, James P.; Running, William; Campos, Silvia B.; Santos, Joseph R.; Phillips, Carrie L.; Molitoris, Bruce A.

In: Journal of the American Society of Nephrology, Vol. 17, No. 10, 01.10.2006, p. 2697-2705.

Research output: Contribution to journalArticle

Sandoval, Ruben M. ; Reilly, James P. ; Running, William ; Campos, Silvia B. ; Santos, Joseph R. ; Phillips, Carrie L. ; Molitoris, Bruce A. / A non-nephrotoxic gentamicin congener that retains antimicrobial efficacy. In: Journal of the American Society of Nephrology. 2006 ; Vol. 17, No. 10. pp. 2697-2705.
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