Received October 27, 2005
Accepted on August 2, 2006

CLINICAL SCIENCE: Cell Biology

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 ^*, and Bruce A. Molitoris ^*¶1

*Indiana University School of Medicine, Division of Nephrology, Indiana Center for Biological Microscopy, Indiana University Department of Pathology & Laboratory Medicine, and ¶Roudebush Veterans Administration Medical Center, Indianapolis, and Indiana University Department of Chemistry, Bloomington, Indiana

¹ To whom correspondence should be addressed. E-mail: bmolitor{at}iupui.edu.

	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.