Summary
The penetration rates of meropenem and imipenem through the outer membrane (OM) of Serratia marcescens was evaluated by the method of Zimmermann and Rosselet. To this aim, two strains of the specie were transformed with the pMON-01 plasmid DNA that carries the bla S gene from Xanthomonas maltophiiia encoding for the L-1 β-lactamase. The permeability of the transformants to cephaloridine was not affected by the presence of the plasmid.
Imipenem was shown to penetrate the OM of the transformants at a rate 4- to 5-fold higher than that of meropenem and close to that of cephaloridine. Meropenem appeared more active than imipenem in inhibiting the targets as inferred from the calculated concentrations of antibiotic in the cell periplasm in the presence of MIC. The calculation of the target access index (TAI) indicated that a 20- to 50-fold decrease in permeability or increase in β-lactamase activity would be required to significantly increase the MICs of imipenem or meropenem for these strains.
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This paper was presented at the 9th Mediterranean Congress of Chemotherapy, Milan, Italy, June 1994.