Beta-lactamase stability and inhibitory activity of meropenem combined with a potent antibacterial activity

H. Nouda, E. T. Harabe, Yoshihiro Sumita, T. Okuda, M. Fukasawa

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The affinity of meropenem for various known types of β-lactamases and its stability to them were tested in comparison with other β-lactams, including imipenem. Meropenem exhibited a marked stability to all β-lactamases tested and was only hydrolyzed by Xanthomonas maltophilia β-lactamase, as were other β-lactams. This was responsible for the potent antibacterial activities of meropenem against β-lactamase-producing strains. Meropenem and imipenem had almost the same, relatively high affinity for β-lactamases; however, they had a lower affinity than clavulanic acid for penicillin β-lactamases and cefoxitin for cephalosporin β-lactamases. Meropenem also had higher β-lactamase inhibitory activity than imipenem. Meropenem inhibited type III (TEM-1), Ia Citrobacter freundii and Ic Proteus vulgaris β-latamases in a progressive manner. Meropenem was thought to be a potent inhibitor of various β-lactamase because of its ability to form stable enzyme-meropenem acyl-complexes. Meropenem generally exhibited a lower induction potential than imipenem against five clinical isolates of C. freundii, Enterobacter cloacae and Pseudomonas aeruginosa, but its induction potential was higher than that of ceftazidime. Meropenem induced, β-lactamases at concentrations above the MIC.

Original languageEnglish
Pages (from-to)218-224
Number of pages7
JournalChemotherapy
Volume38
Issue number4
DOIs
Publication statusPublished - Jan 1 1992
Externally publishedYes

Fingerprint

meropenem
beta-Lactamases
Imipenem
Citrobacter freundii
Lactams
Proteus vulgaris
Stenotrophomonas maltophilia
Enterobacter cloacae
Cefoxitin
Clavulanic Acid
Ceftazidime

Keywords

  • B-lactamase induction
  • Meropenem
  • β-lactamase inhibition
  • β-lactamase stability

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Beta-lactamase stability and inhibitory activity of meropenem combined with a potent antibacterial activity. / Nouda, H.; Harabe, E. T.; Sumita, Yoshihiro; Okuda, T.; Fukasawa, M.

In: Chemotherapy, Vol. 38, No. 4, 01.01.1992, p. 218-224.

Research output: Contribution to journalArticle

Nouda, H. ; Harabe, E. T. ; Sumita, Yoshihiro ; Okuda, T. ; Fukasawa, M. / Beta-lactamase stability and inhibitory activity of meropenem combined with a potent antibacterial activity. In: Chemotherapy. 1992 ; Vol. 38, No. 4. pp. 218-224.
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