In Vitro Activities of Daptomycin Combined with Fosfomycin or Rifampin on Planktonic and Adherent Linezolid-resistant Enterococcus faecalis

Abstract

This study aimed to explore daptomycin combined with fosfomycin or rifampin against the planktonic and adherent linezolid-resistant isolates of Enterococcus faecalis. Four linezolid-resistant isolates of E. faecalis which formed biofilms were collected for this study. Biofilm biomasses were detected by crystal violet staining. The adherent cells in the mature biofilms were counted by CFU numbers and observed by confocal laser scanning microscope (CLSM). In time-killing studies, daptomycin combined with fosfomycin or rifampin (4xMIC) demonstrated bactericidal activities on the planktonic cells, and daptomycin combined with fosfomycin killed more planktonic cells (at least 2-log10 CFU/ml) than daptomycin or fosfomycin alone. Daptomycin alone showed activities against the mature biofilms, and daptomycin combined with fosfomycin (16xMIC) demonstrated significantly more activity than daptomycin or fosfomycin alone against the mature biofilms in three of the four isolates. Daptomycin alone effectively killed the adherent cells, and daptomycin combined with fosfomycin (16xMIC) killed more adherent cells than daptomycin or fosfomycin alone in these mature biofilms. The high concentrations of daptomycin (512 mg/L) combined with fosfomycin indicated more activity than 16xMIC of daptomycin combined with fosfomycin on the adherent cells and the mature biofilms. The addition of rifampin increased the activity of daptomycin against the biofilms and the adherent cells of FB-14 and FB-80 isolates, but was not observed in FB-1 and FB-2 isolates. In conclusion, daptomycin combined with fosfomycin works effectively against the planktonic and adherent linezolid-resistant isolates of E. faecalis. The role of rifampin in these linezolid-resistant isolates is discrepant and needs more studies.