Document Report Card

ID: ALA1671863

Journal: Antimicrob Agents Chemother

Title: Inhibition of OXA-1 beta-lactamase by penems.

Authors: Bethel CR, Distler AM, Ruszczycky MW, Carey MP, Carey PR, Hujer AM, Taracila M, Helfand MS, Thomson JM, Kalp M, Anderson VE, Leonard DA, Hujer KM, Abe T, Venkatesan AM, Mansour TS, Bonomo RA.

Abstract: The partnering of a beta-lactam with a beta-lactamase inhibitor is a highly effective strategy that can be used to combat bacterial resistance to beta-lactam antibiotics mediated by serine beta-lactamases (EC 3.2.5.6). To this end, we tested two novel penem inhibitors against OXA-1, a class D beta-lactamase that is resistant to inactivation by tazobactam. The K(i) of each penem inhibitor for OXA-1 was in the nM range (K(i) of penem 1, 45 +/- 8 nM; K(i) of penem 2, 12 +/- 2 nM). The first-order rate constant for enzyme and inhibitor complex inactivation of penems 1 and 2 for OXA-1 beta-lactamase were 0.13 +/- 0.01 s(-1) and 0.11 +/- 0.01 s(-1), respectively. By using an inhibitor-to-enzyme ratio of 1:1, 100% inactivation was achieved in

CiteXplore: 18559643

DOI: 10.1128/aac.01677-07