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Antimicrobial Agents and Chemotherapy, August 2003, p. 2615-2618, Vol. 47, No. 8
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.8.2615-2618.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of Novel Oxapenems, Alone and in Combination with Ceftazidime, against Gram-Positive and Gram-Negative Organisms

Conor E. Jamieson,1 Peter A. Lambert,1* and Iain N. Simpson2

Life and Health Sciences, Aston University, Birmingham,1 Micron Research, Cambridge, United Kingdom2

Received 3 June 2002/ Returned for modification 17 February 2003/ Accepted 10 May 2003

Four novel oxapenem compounds (i.e., AM-112, AM-113, AM-114, and AM-115) were investigated for their ß-lactamase inhibitory activity against a panel of isolated class A, C, and D enzymes, which included expanded-spectrum ß-lactamase enzymes (ESBLs). The oxapenems were potent ß-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 ß-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.

* Corresponding author. Mailing address: Life and Health Sciences, Aston University, Birmingham B4 7ET, United Kingdom. Phone: 44 121 3593611, ext. 4471. Fax: 44 121 3590572. E-mail: p.a.lambert{at}aston.ac.uk.

Antimicrobial Agents and Chemotherapy, August 2003, p. 2615-2618, Vol. 47, No. 8
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.8.2615-2618.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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