Relative importances of outer membrane permeability and group 1 beta-lactamase as determinants of meropenem and imipenem activities against Enterobacter cloacae

Antimicrob Agents Chemother. 1995 Feb;39(2):350-5. doi: 10.1128/AAC.39.2.350.


The roles of outer membrane permeability and Bush group 1 beta-lactamase activity in determining Enterobacter cloacae susceptibility to either meropenem or imipenem were investigated. A beta-lactamase-deficient strain was obtained by mutagenesis from a clinical isolate of E. cloacae, and a porin-deficient strain was selected from this mutant with cefoxitin. Both strains were transformed with the plasmid pAA20R, which contained the gene coding for the carbapenem-hydrolyzing CphA beta-lactamase, and the carbapenem permeability coefficients were measured by the Zimmermann and Rosselet technique (W. Zimmermann and A. Rosselet, Antimicrob. Agents Chemother. 12:368-372, 1977). The permeability coefficient of meropenem was roughly half that of imipenem in the normally permeable strain and almost seven times lower than that of imipenem in the porin-deficient strain. In the porin-deficient strain, the virtual absence of porins caused the MICs of meropenem to increase from 8 to 16 times, while it did not affect the MICs of imipenem. Conversely, the beta-lactamase affected imipenem but not meropenem activity: meropenem showed a similar activity in the parent strain and in the beta-lactamase-deficient mutant with both a low- and high-density inoculum, whereas imipenem was 16 times less active against the parent strain when the high-density inoculum was used. It is concluded that outer membrane permeability and stability to group 1 beta-lactamase have different impacts on the activities of meropenem and imipenem against E. cloacae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins*
  • Cell Membrane Permeability*
  • Cephalosporinase / physiology
  • Enterobacter cloacae / drug effects*
  • Imipenem / pharmacokinetics
  • Imipenem / pharmacology*
  • Meropenem
  • Porins / analysis
  • Thienamycins / pharmacokinetics
  • Thienamycins / pharmacology*
  • beta-Lactamases / physiology*


  • Bacterial Proteins
  • Porins
  • Thienamycins
  • Imipenem
  • Cephalosporinase
  • beta-Lactamases
  • carbapenemase
  • Meropenem