Mode of action of meropenem, a new carbapenem antibiotic

Yoshihiro Sumita, Eiko Tada, Hiroshi Nouda, Takao Okuda, Masatomo Fukasawa

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


We investigated the binding affinities of meropenem (MEPM) for penicillin-binding proteins (PBPs) and the morphological changes induced by it in Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, and also examined the inhibitory and inducible activity of MEPM against various β-lactamases in comparison with other β-lactams, including imipenem (IPM). MEPM bound strongly to PBP-4, 2, 1 A, 1Bs, 5 and 6 in E. coli and PBP-4, 3, 2, 1 A, 1B and 5 in P. aeruginosa, in descending order of binding strength. The affinities of MEPM for PBP-3 in both species were higher than those of IPM. Against S. aureus MEPM had the highest affinity for PBP-4, followed by 1, 2 and 3. MEPM induced spherical cells in E. coli at concentrations lower than the MIC, and at 4-fold MIC, it induced an indeterminate form, whereas IPM did not. Against P. aeruginosa, MEPM induced filamentous cell formation at concentrations lower than its MIC, bulge cell formation at 2-fold MIC, and round cell formation at 4-fold MIC. These responses were different from the round cell formation generally induced in both organisms by IPM at each concentration. These morphological differences in E. coli and P. aeruginosa may be due to differences in the binding profiles to PBPs-2 and 3. MEPM possessed marked stability against types I, III and V β-lactamases from 15 organisms. MEPM also showed β-lactamase inhibitory activity and formed more stable MEPM enzyme acyl-complexes than IPM. Although MEPM showed relatively high β-lactamese induction, its induction potential was generally lower than that of IPM but higher than that of ceftazidime. MEPM induced β-lactamases at concentrations higher than the MIC.

Original languageEnglish
Pages (from-to)90-102
Number of pages13
Publication statusPublished - Apr 1992
Externally publishedYes


  • Meropenem
  • PBP
  • β-lactamase

ASJC Scopus subject areas

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


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