In vitro activities of novel oxapenems, alone and in combination with ceftazidime, against gram-positive and gram-negative organisms

Jamieson, Conor E., Lambert, Peter A. and Simpson, Iain N. (2003). In vitro activities of novel oxapenems, alone and in combination with ceftazidime, against gram-positive and gram-negative organisms. Antimicrobial Agents and Chemotherapy, 47 (8), pp. 2615-2618.

Abstract

Four novel oxapenem compounds (i.e., AM-112, AM-113, AM-114, and AM-115) were investigated for their β-lactamase inhibitory activity against a panel of isolated class A, C, and D enzymes, which included expanded-spectrum β-lactamase enzymes (ESBLs). The oxapenems were potent β-lactamase inhibitors. Activity varied within the group, with AM-113 and AM-114 proving to be the most active compounds. The 50% inhibitory concentrations for these agents were up to 100,000-fold lower than that of clavulanic acid against class C and D enzymes. As a group, the oxapenems were more potent than clavulanic acid against enzymes from all classes. The ability of these compounds to protect ceftazidime from hydrolysis by β-lactamase-producing strains was evaluated by MIC tests that combined ceftazidime and each oxapenem in a 1:1 or 2:1 ratio. The oxapenems markedly reduced the MICs for ceftazidime against class C hyperproducing strains and strains producing TEM- and SHV-derived ESBLs. There was little difference between the activity of 1:1 and 2:1 combinations of ceftazidime and oxapenem. The oxapenems failed to enhance the activity of ceftazidime against derepressed AmpC-producing Pseudomonas aeruginosa strains.

Publication DOI: https://doi.org/10.1128/AAC.47.8.2615-2618.2003
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
Uncontrolled Keywords: oxapenem compounds,β-lactamase,inhibitory activity,enzymes,expanded-spectrum β-lactamase enzymes,β-lactamase inhibitors,clavulanic acid,Pharmacology (medical)
Full Text Link: http://www.ncbi ... cles/PMC166081/
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2003-08
Authors: Jamieson, Conor E.
Lambert, Peter A. ( 0000-0002-8243-2741)
Simpson, Iain N.

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