+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



Antimicrobial Agents and ChemoTherapy 43(5): 1170-1176



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 microgram/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 microgram/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 microgram/ml under all test conditions.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 046359820

Download citation: RISBibTeXText

PMID: 10223931


Related references

In Vitro Activities of the Potent, Broad-Spectrum Carbapenem Mk-0826 (L-749,345) against Broad-Spectrum -Lactamase-and Extended-Spectrum -Lactamase-Producing Klebsiella pneumoniae and Escherichia coli Clinical Isolates. Antimicrobial Agents and Chemotherapy 43(5): 1170-1176, 1999

In vitro activity of the potent, broad-spectrum carbapenem L-749,345 against BDS-beta-L- and ES-beta-L-producing Escherichia coli and Klebsiella pneumoniae clinical isolates. Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 36(0): 121, 1996

In vitro activities of 16 antimicrobial agents against clinical isolates of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in two regional hospitals in Taiwan. Journal of Microbiology, Immunology, and Infection 39(1): 59-66, 2006

Effects of inoculum and beta-lactamase activity in AmpC- and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae clinical isolates tested by using NCCLS ESBL methodology. Journal of Clinical Microbiology 42(1): 269-275, 2004

In vitro activity of ceftiofur tested against clinical isolates of Escherichia coli and Klebsiella pneumoniae including extended spectrum beta-lactamase producing strains. International Journal of Antimicrobial Agents 15(4): 271-275, 2000

Clinical outcome of patients with extended-spectrum beta-lactamase -producing Klebsiella pneumoniae and Escherichia coli bacteremia after treatment with expanded-spectrum cephalosporins. Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 39: 166, 1999

The prevalence of extended-spectrum beta lactamase-producing Escherichia coli and Klebsiella pneumoniae in clinical isolates and risk factors. Saudi Medical Journal 27(5): 608-612, 2006

In vitro activity of ertapenem and other carbapenems against extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae clinical isolates in a tertiary care center in Turkey. Expert Opinion on PharmacoTherapy 9(9): 1441-1449, 2008

Molecular characteristics of extended spectrum beta-lactamases in Escherichia coli and Klebsiella pneumoniae and the prevalence of qnr in Extended spectrum beta-lactamase isolates in a tertiary care hospital in Korea. Yonsei Medical Journal 51(5): 768-774, 2010

The prevalence of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae among clinical isolates from a general hospital in Iran. Acta Microbiologica et Immunologica Hungarica 56(1): 89-99, 2009

Molecular epidemiology of plasmid spread among extended broad-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates in a pediatric hospital. Journal of Clinical Microbiology 31(2): 179-184, 1993

Comparative assessment of inoculum effects on the antimicrobial activity of amoxycillin-clavulanate and piperacillin-tazobactam with extended-spectrum beta-lactamase-producing and extended-spectrum beta-lactamase-non-producing Escherichia coli isolates. Clinical Microbiology and Infection 16(2): 132-136, 2010

Emergence of multidrug-resistant Klebsiella pneumoniae isolates producing VIM-4 metallo-beta-lactamase, CTX-M-15 extended-spectrum beta-lactamase, and CMY-4 AmpC beta-lactamase in a Tunisian university hospital. Antimicrobial Agents and ChemoTherapy 50(12): 4198-4201, 2006

Cefoxitin as a carbapenem-sparing antibiotic for infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae. Infectious Diseases 47(11): 789-795, 2016

Carbapenem Therapy for Bacteremia Due to Extended-Spectrum-beta-Lactamase-Producing Escherichia coli or Klebsiella pneumoniae Implications of Ertapenem Susceptibility. 2012