In vitro synergistic effect of retapamulin with erythromycin and quinupristin against Enterococcus faecalis

To find a therapeutic alternative for the treatment of skin and soft tissue infections, we evaluated the effects of combinations of retapamulin with macrolide, lincosamide, and streptogramin (MLS) antibiotics against Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecium, and Enterococcus faecalis. Using both the disk diffusion test and checkerboard assay, we initially examined the effects of combinations of retapamulin with MLS antibiotics against standard strains of these species. Combinations of retapamulin with erythromycin, quinupristin/dalfopristin and quinupristin showed synergistic activity against E. faecalis only. Synergy of retapamulin with clindamycin and dalfopristin was not observed. Then, a checkerboard assay was performed to evaluate the effects of the combinations against 15 clinical strains of E. faecalis. Retapamulin and quinupristin, the most synergistic combination, showed activity against all erythromycin-susceptible, -intermediate, and -resistant strains tested. Among the eight strains with high-level erythromycin resistance, five strains were synergistically inhibited in the presence of only 1 μg of retapamulin per ml. Time-kill assay revealed that combinations of retapamulin with erythromycin and quinupristin were bacteriostatic. These results suggest that combinations of retapamulin with erythromycin and quinupristin have in vitro synergistic activity against E. faecalis, including strains with high-level erythromycin resistance.