INVITRO SELECTION OF HIGH-LEVEL IMIPENEM-RESISTANT (IMP-R) - BETA-LACTAMASE PRODUCING STRAINS OF BACTEROIDES-FRAGILIS

For several years, GEEP has been monitoring the antibiotic susceptibility of clinical strains of B. fragilis isolated in France. In 1988, the first high level Imp-R (CMI greater-than-or-equal-to 128 mg/l) clinical isolates were observed (3 strains); in 1989, 7 additional Imp-R strains were collected. In order to study the location of the resistance gene(s) and the mechanism(s) involved, several experiments have been carried out including conjugation, plasmid analysis and in vitro selection of mutants. We have not succeeded in transferring Imp-R to susceptible strains by conjugation, using conditions where other resistance markers were transferred. We have observed several apparently plasmid-free Imp-R strains. Imp-R derivatives (MIC greater-than-or-equal-to 128 mg/l) were selected in vitro from 2 sensitive strains (MIC less-than-or-equal-to 2 mg/l), possibly after a one step-mutation. Preliminary analysis using the method of Rolfe and Finegold (J. Infect. Dis., 1983, 147, 227-37) has shown the possession by the Imp-R derivatives of a mechanism capable of efficiently inactivating Imp. As far as Imp inactivation is concerned, the in vitro generated Imp-R derivatives cannot be distinguished from the clinical Imp-R strains. Biochemical analysis of beta-lactamases produced by the strains is under way.