Mechanisms responsible for reduced susceptibility to imipenem in Bacteroides fragilis

The mechanisms responsible for reduced susceptibility to imipenem (MIC 2-16 mg/L) were investigated in eight strains of Bacteroides fragilis. All the strains produced elevated levels of beta-lactamase. Four B. fragilis strains produced metallo-beta-lactamase capable of marked imipenem hydrolysis, and these enzymes were shown to be responsible for resistance. There was evidence, from testing susceptibility to imipenem in the presence of clavulanic acid, that increased resistance in two strains was associated with susceptibility to beta-lactamases other than metallo-enzymes. With the remaining two strains there was no evidence of enzymic breakdown of imipenem. Neither of these strains showed evidence of decreased permeability to nitrocefin as judged by a method which takes into account the substrate concentration in the periplasmic space. A low molecular weight PBP, that was not seen in fully sensitive strains of B. fragilis, was detected in four strains in which reduced susceptibility to imipenem was not associated with metallo-beta-lactamase activity.