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

Conor E. Jamieson, Peter A. Lambert*, Iain N. Simpson

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2615-2618
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume47
Issue number8
DOIs
Publication statusPublished - Aug 2003

Keywords

  • oxapenem compounds
  • β-lactamase
  • inhibitory activity
  • enzymes
  • expanded-spectrum β-lactamase enzymes
  • β-lactamase inhibitors
  • clavulanic acid

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