Journal of Drug Metabolism & Toxicology
Open Access

Using synergies to potentiate drugs such as vancomycin in gram negative bacteria

World Congress and Exhibition on Antibiotics

September 14-16, 2015 Las Vegas, USA

Jeffrey H Miller

University of California, USA

Keynote: J Drug Metab Toxicol

Abstract :

Vancomycin (VAN) is an effective antibiotic against certain multi-drug resistant Gram-positive pathogens, such as MRSA (methicillin-resistant Staphylococcus aureus). The large size of this glycopeptide precludes it from penetrating the outer membrane of Gram-negative cells, rendering it ineffective against Gram-negative infections. However, a very small amount of VAN does enter Gram-negative cells. We sought to exploit this small concentration by finding synergies with approved drugs. We have detected strong synergies in the Gram-negative Escherichia coli between VAN and nitrofurantoin (NIT), and also trimethoprim (TMP). Concentrations of VAN as low as 12.5 �¼g/ml can display an effect with NIT and concentrations of VAN of 6.25 �¼g/ml can show effects with TMP. Combinations of approved drugs that are already in use offer important advantages over screening for new drugs, as the former can be applied in a clinical setting with far less delays. We have also used synergy in pairwise drug interactions to examine models of antibiotic mechanism of action and to understand the mechanism of synergy itself.

Biography :

Jeffrey H Miller is a distinguished Professor in Microbiology, Immunology, & Molecular Genetics in the University of California, Los Angeles. He completed his Postdoc in the Harvard Medical School, Boston, MA. In 2011 he is elected as a member of the American Academy of Arts and Sciences.

Email: jhmiller@microbio.ucla.edu