title: Relative importances of outer membrane permeability and group 1 beta-lactamase as determinants of meropenem and imipenem activities against Enterobacter cloacae.
abstract: 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.
authors.affiliation: Università degli Studi di Verona, Istituto di Microbiologia, Verona, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cornaglia
authors.forename: K
authors.initials: K
authors.lastname: Russell
authors.forename: G
authors.initials: G
authors.lastname: Satta
authors.forename: R
authors.initials: R
authors.lastname: Fontana
mesh_terms: D001426:Bacterial Proteins; D002463:Cell Membrane Permeability; D002510:Cephalosporinase / Q000502:physiology; D016972:Enterobacter cloacae / Q000187:drug effects*; D015378:Imipenem / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077731:Meropenem; D018272:Porins / Q000032:analysis; D013845:Thienamycins / Q000493:pharmacokinetics / Q000494:pharmacology*; D001618:beta-Lactamases / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D018272:Porins; D013845:Thienamycins; D015378:Imipenem; D002510:Cephalosporinase; D001618:beta-Lactamases; C063912:carbapenemase; D000077731:Meropenem