SUPPRESSION OF BETA-LACTAM ANTIBIOTIC-RESISTANCE IN A METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS THROUGH SYNERGIC ACTION OF EARLY CELL-WALL INHIBITORS AND SOME OTHER ANTIBIOTICS

We tested the effect of a number of mechanistically distinct antibacte rial agents on the expression of methicillin resistance in a highly an d homogeneously resistant strain of methicillin-resistant Staphylococc us aureus. The antibiotics, used at 0.25 x MIG, included inhibitors of early steps in peptidoglycan synthesis (fosfomycin, beta-chloro-D-ala nine, D-cycloserine); bacitracin; teicoplanin and vancomycin; beta-lac tam inhibitors chosen on the basis of their relatively selective affin ities for penicillin-binding proteins 1, 2, 3 and 4 of S. aureus (imip enem, cefotaxime, cephradine and cefoxitin); compounds that inhibit va rious steps in protein synthesis (tetracycline, chloramphenicol, genta micin, erythromycin and quinupristin/dalfopristin) and an inhibitor of DNA gyrase (temafloxacin). All inhibitors of early cell wall synthesi s caused reduction of methicillin resistance and change from the homog eneous to the heterogeneous methicillin-resistant phenotype. Similar e ffects were obtained with only cephradine out of the four beta-lactams tested, and with erythromycin and quinupristin/dalfopristin as well. The other inhibitors of protein synthesis and DNA gyrase had no effect .