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Antimicrobial Agents and Chemotherapy, October 2001, p. 2831-2837, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2831-2837.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Activity of Ertapenem (MK-0826) versus Enterobacteriaceae with Potent beta -Lactamases

David M. Livermore,* Karen J. Oakton, Michael W. Carter, and Marina Warner

Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory, London NW9 5HT, United Kingdom

Received 30 January 2001/Returned for modification 8 May 2001/Accepted 13 July 2001

Ertapenem (MK-0826; L-749,345), a new carbapenem with a long serum half-life, was tested, in vitro, against beta -lactamase-producing bacteria. The new compound had a MIC at which 90% of the isolates were inhibited of 0.06 µg/ml for extended-spectrum beta -lactamase (ESBL)-producing klebsiellas, compared with 0.5 µg/ml for imipenem, 16 µg/ml for cefepime, and >128 µg/ml for ceftazidime and piperacillin-tazobactam. MICs of ertapenem for AmpC-derepressed mutant Enterobacteriaceae were 0.015 to 0.5 µg/ml, whereas imipenem MICs were 0.25 to 1 µg/ml and those of cefepime were 0.5 to 4 µg/ml, and resistance to ceftazidime and piperacillin-tazobactam was generalized. Despite this good activity, the MICs of ertapenem for ESBL-positive klebsiellas mostly were two- to fourfold above those for ESBL-negative strains, and the MICs for AmpC-hyperproducing Enterobacter cloacae and Citrobacter freundii mutants exceeded those for the corresponding AmpC-basal mutants. These differentials did not increase when the inoculum was raised from 104 to 106 CFU/spot, contraindicating significant lability. Carbapenemase producers were also tested. The IMP-1 metallo-beta -lactamase conferred substantial ertapenem resistance (MIC, 128 µg/ml) in a porin-deficient Klebsiella pneumoniae strain, whereas a MIC of 6 µg/ml was recorded for its porin-expressing revertant. SME-1 carbapenemase was associated with an ertapenem MIC of 2 µg/ml for Serratia marcescens S6, compared with <0.03 µg/ml for Serratia strains lacking this enzyme. In summary, ertapenem had good activity against strains with potent beta -lactamases, except for those with known carbapenemases.

* Corresponding author. Mailing address: Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory, 61 Colindale Ave., London NW9 5HT, United Kingdom. Phone: 44 (0)20-8200-4400. Fax: 44 (0)20-8358-3292. E-mail: DLivermore{at}phls.org.uk.

Antimicrobial Agents and Chemotherapy, October 2001, p. 2831-2837, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2831-2837.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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