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Antimicrobial Agents and Chemotherapy, June 2001, p. 1860-1867, Vol. 45, No. 6
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.6.1860-1867.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

In Vitro Activities of Ertapenem (MK-0826) against Recent Clinical Bacteria Collected in Europe and Australia

David M. Livermore,1,* Michael W. Carter,1 Simone Bagel,2 Bernd Wiedemann,2 Fernando Baquero, Elena Loza,3 Hubert P. Endtz,4 Nicole van den Braak,4 Clarence J. Fernandes,5 Lorna Fernandes,5 Niels Frimodt-Moller,6 Laura S. Rasmussen,6 Helen Giamarellou,7 Evangelos Giamarellos-Bourboulis,7 Vincent Jarlier,8 Jacqueline Nguyen,8 Carl-Erik Nord,9 Marc J. Struelens,10 Caire Nonhoff,10 John Turnidge,11 Jan Bell,11 Reinhard Zbinden,12 Stefan Pfister, Lori Mixson,13 and Daniel L. Shungu14

Antibiotic Resistance Monitoring & Reference Laboratory, Central Public Health Laboratory, London, United Kingdom1; Pharmazeutische Mikrobiologie, Bonn, Germany2; Servicio de Microbiologia, Hospital Ramon y Cajal, Madrid, Spain3; Afdeling Medische Microbiologir & Infectieziekten, Academisch Ziekenhuis Totterdam, Rotterdam, The Netherlands4; Microbiology Department, Pacific Laboratory Medicine Services, Royal North Shore Hospital, St. Leonards, New South Wales5 and Microbiology and Infectious Diseases, Women's and Children's Hospital, North Adelaide, South Australia,11 Australia; Department of Clinical Microbiology, Statens Serum Institut, Copenhagen, Denmark6; Department of Internal Medicine, Athens Medical School, Athens, Greece7; Laboratoire de Bacteriologie, Faculte de Medecine, Pitie-Salpetriere, Paris, France8; Department of Microbiology, Huddinge University Hospital, Huddinge, Sweden9; Universite Libre de Bruxelles, Clinique Universitaire, Brussels, Belgium10; Department of Medical Microbiology, University of Zurich, Zurich, Switzerland12; and Biometrics Research,13 and Infectious Diseases, Clinical Microbiology Services,14 Merck Research Laboratories, Rahway, New Jersey

Received 5 December 2000/Returned for modification 15 January 2001/Accepted 12 March 2001

Ertapenem (MK-0826, L-749,345) is a 1-beta -methyl carbapenem with a long serum half-life. Its in vitro activity was determined by broth microdilution against 3,478 bacteria from 12 centers in Europe and Australia, with imipenem, cefepime, ceftriaxone, and piperacillin-tazobactam used as comparators. Ertapenem was the most active agent tested against members of the family Enterobacteriaceae, with MICs at which 90% of isolates are inhibited (MIC90s) of <= 1 µg/ml for all species. Ertapenem also was more active than imipenem against fastidious gram-negative bacteria and Moraxella spp.; on the other hand, ertapenem was slightly less active than imipenem against streptococci, methicillin-susceptible staphylococci, and anaerobes, but its MIC90s for these groups remained <= 0.5 µg/ml. Acinetobacter spp. and Pseudomonas aeruginosa were also much less susceptible to ertapenem than imipenem, and most Enterococcus faecalis strains were resistant. Ertapenem resistance, based on a provisional NCCLS MIC breakpoint of >= 16 µg/ml, was seen in only 3 of 1,611 strains of the family Enterobacteriaceae tested, all of them Enterobacter aerogenes. Resistance was also seen in 2 of 135 anaerobes, comprising 1 Bacteroides fragilis strain and 1 Clostridium difficile strain. Ertapenem breakpoints for streptococci have not been established, but an unofficial susceptibility breakpoint of <= 2 µg/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were as high as 2 µg/ml. Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 µg/ml and one required an MIC of 4 µg/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 µg/ml. These streptococci also had diminished susceptibilities to other beta -lactams, including imipenem as well as ertapenem. The Etest and disk diffusion gave susceptibility test results in good agreement with those of the broth microdilution method for ertapenem.

* Corresponding author. Mailing address: Antibiotic Resistance Monitoring & 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.nhs.uk.

Antimicrobial Agents and Chemotherapy, June 2001, p. 1860-1867, Vol. 45, No. 6
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.6.1860-1867.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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