This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kohler, J.
Right arrow Articles by Silver, L. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kohler, J.
Right arrow Articles by Silver, L. L.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 1999, p. 1170-1176, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

In Vitro Activities of the Potent, Broad-Spectrum Carbapenem MK-0826 (L-749,345) against Broad-Spectrum beta -Lactamase-and Extended-Spectrum beta -Lactamase-Producing Klebsiella pneumoniae and Escherichia coli Clinical Isolates

Joyce Kohler,1,* Karen L. Dorso,1 Katherine Young,1 Gail G. Hammond,2 Hugh Rosen,1 Helmut Kropp,1 and Lynn L. Silver1

Departments of Infectious Diseases1 and Biochemistry,2 Merck Research Laboratories, Rahway, New Jersey 07065-0900

Received 6 April 1998/Returned for modification 5 August 1998/Accepted 3 March 1999

An important mechanism of bacterial resistance to beta -lactam antibiotics is inactivation by beta -lactam-hydrolyzing enzymes (beta -lactamases). The evolution of the extended-spectrum beta -lactamases (ESBLs) is associated with extensive use of beta -lactam antibiotics, particularly cephalosporins, and is a serious threat to therapeutic efficacy. ESBLs and broad-spectrum beta -lactamases (BDSBLs) are plasmid-mediated class A enzymes produced by gram-negative pathogens, principally Escherichia coli and Klebsiella pneumoniae. MK-0826 was highly potent against all ESBL- and BDSBL-producing K. pneumoniae and E. coli clinical isolates tested (MIC range, 0.008 to 0.12 µg/ml). In E. coli, this activity was associated with high-affinity binding to penicillin-binding proteins 2 and 3. When the inoculum level was increased 10-fold, increasing the amount of beta -lactamase present, the MK-0826 MIC range increased to 0.008 to 1 µg/ml. By comparison, similar observations were made with meropenem while imipenem MICs were usually less affected. Not surprisingly, MIC increases with noncarbapenem beta -lactams were generally substantially greater, resulting in resistance in many cases. E. coli strains that produce chromosomal (Bush group 1) beta -lactamase served as controls. All three carbapenems were subject to an inoculum effect with the majority of the BDSBL- and ESBL-producers but not the Bush group 1 strains, implying some effect of the plasmid-borne enzymes on potency. Importantly, MK-0826 MICs remained at or below 1 µg/ml under all test conditions.

* Corresponding author. Mailing address: Merck Research Laboratories, RY80Y-225, P.O. Box 2000, Rahway, NJ 07065-0900. Phone: (732) 594-5292. Fax: (732) 594-5878. E-mail: joyce_kohler{at}merck.com.

Antimicrobial Agents and Chemotherapy, May 1999, p. 1170-1176, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • DeRyke, C. A., Banevicius, M. A., Fan, H. W., Nicolau, D. P. (2007). Bactericidal Activities of Meropenem and Ertapenem against Extended-Spectrum-{beta}-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in a Neutropenic Mouse Thigh Model. Antimicrob. Agents Chemother. 51: 1481-1486 [Abstract] [Full Text]  
  • Maglio, D., Banevicius, M. A., Sutherland, C., Babalola, C., Nightingale, C. H., Nicolau, D. P. (2005). Pharmacodynamic Profile of Ertapenem against Klebsiella pneumoniae and Escherichia coli in a Murine Thigh Model. Antimicrob. Agents Chemother. 49: 276-280 [Abstract] [Full Text]  
  • Alhambra, A., Cuadros, J. A., Cacho, J., Gomez-Garces, J. L., Alos, J. I. (2004). In vitro susceptibility of recent antibiotic-resistant urinary pathogens to ertapenem and 12 other antibiotics. J Antimicrob Chemother 53: 1090-1094 [Abstract] [Full Text]  
  • Mushtaq, S., Ge, Y., Livermore, D. M. (2004). Comparative Activities of Doripenem versus Isolates, Mutants, and Transconjugants of Enterobacteriaceae and Acinetobacter spp. with Characterized {beta}-Lactamases. Antimicrob. Agents Chemother. 48: 1313-1319 [Abstract] [Full Text]  
  • Livermore, D. M., Sefton, A. M., Scott, G. M. (2003). Properties and potential of ertapenem. J Antimicrob Chemother 52: 331-344 [Abstract] [Full Text]  
  • Goldstein, E. J. C., Citron, D. M., Merriam, C. V., Warren, Y. A., Tyrrell, K. L., Fernandez, H. (2002). Comparative In Vitro Activities of Ertapenem (MK-0826) against 469 Less Frequently Identified Anaerobes Isolated from Human Infections. Antimicrob. Agents Chemother. 46: 1136-1140 [Abstract] [Full Text]  
  • Goldstein, E. J. C., Citron, D. M., Merriam, C. V., Warren, Y. A., Tyrrell, K., Fernandez, H. (2001). Comparative in vitro activity of ertapenem and 11 other antimicrobial agents against aerobic and anaerobic pathogens isolated from skin and soft tissue animal and human bite wound infections. J Antimicrob Chemother 48: 641-651 [Abstract] [Full Text]  
  • Livermore, D. M., Oakton, K. J., Carter, M. W., Warner, M. (2001). Activity of Ertapenem (MK-0826) versus Enterobacteriaceae with Potent {beta}-Lactamases. Antimicrob. Agents Chemother. 45: 2831-2837 [Abstract] [Full Text]  
  • Betriu, C., Sanchez, A., Palau, M. L., Gomez, M., Picazo, J. J. (2001). In Vitro Activities of MK-0826 and 16 Other Antimicrobials against Bacteroides fragilis Group Strains. Antimicrob. Agents Chemother. 45: 2372-2374 [Abstract] [Full Text]  
  • Livermore, D. M., Carter, M. W., Bagel, S., Wiedemann, B., Baquero, F., Loza, E., Endtz, H. P., van den Braak, N., Fernandes, C. J., Fernandes, L., Frimodt-Moller, N., Rasmussen, L. S., Giamarellou, H., Giamarellos-Bourboulis, E., Jarlier, V., Nguyen, J., Nord, C.-E., Struelens, M. J., Nonhoff, C., Turnidge, J., Bell, J., Zbinden, R., Pfister, S., Mixson, L., Shungu, D. L. (2001). In Vitro Activities of Ertapenem (MK-0826) against Recent Clinical Bacteria Collected in Europe and Australia. Antimicrob. Agents Chemother. 45: 1860-1867 [Abstract] [Full Text]  
  • Fuchs, P. C., Barry, A. L., Brown, S. D. (2001). In Vitro Activities of Ertapenem (MK-0826) against Clinical Bacterial Isolates from 11 North American Medical Centers. Antimicrob. Agents Chemother. 45: 1915-1918 [Abstract] [Full Text]  
  • Yamazaki, M., Neway, W. E., Ohe, T., Chen, I-W., Rowe, J. F., Hochman, J. H., Chiba, M., Lin, J. H. (2001). In Vitro Substrate Identification Studies for P-glycoprotein-Mediated Transport: Species Difference and Predictability of in Vivo Results. J. Pharmacol. Exp. Ther. 296: 723-735 [Abstract] [Full Text]  
  • Goldstein, E. J. C., Citron, D. M., Vreni Merriam, C., Warren, Y., Tyrrell, K. L. (2000). Comparative In Vitro Activities of Ertapenem (MK-0826) against 1,001 Anaerobes Isolated from Human Intra-Abdominal Infections. Antimicrob. Agents Chemother. 44: 2389-2394 [Abstract] [Full Text]  
  • Wexler, H. M., Molitoris, D., Finegold, S. M. (2000). In Vitro Activities of MK-826 (L-749,345) against 363 Strains of Anaerobic Bacteria. Antimicrob. Agents Chemother. 44: 2222-2224 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»