Synergy and mechanism of interaction between pefloxacin and penicillin G against enterococci

In vitro synergy between penicillin and pefloxacin against Enterococcus hirae and Enterococcus faecium strains with different penicillin susceptibility was studied. The combination was synergistic against penicillin-resistant strains, E. hirae R40 and E. faecium 28R, but not against the penicillin-susceptible ones (E. hirae ATCC 9790 and E. faecium 28S). Analysis of PBPs of cells, grown in the presence of pefloxacin, showed that PBP5 of penicillin-resistant strains, the PBP responsible for the resistance of enterococci to beta-lactam antibiotics, is consistently reduced while it is almost unaffected in the penicillin-susceptible strains even at the highest concentrations of pefloxacin. These results indicate that pefloxacin interferes with the mechanism of synthesis of PBPs and particularly of PBP5, a protein whose production has already been modified in resistant strains, in some way rectifing the previous alteration.