In vitro activities of daptomycin combined with fosfomycin or rifampin on planktonic and adherent linezolid-resistant isolates of Enterococcus faecalis

Purpose: This study aimed to explore daptomycin combined with fosfomycin or rifampin against the planktonic and adherent linezolid-resistant isolates of Enterococcus faecalis.

Methodology: Four linezolid-resistant and four linezolid-sensitive isolates of E. faecalis which formed biofilms were collected for this study. Biofilm biomasses were detected by crystal violet staining and the adherent cells in the mature biofilms were quantified by c.f.u. determination.

Results: Daptomycin alone, or combined with fosfomycin or rifampin (4×MIC) demonstrated bactericidal activities on the planktonic cells, and daptomycin combined with fosfomycin killed more planktonic cells (at least 1-log10 c.f.u. ml^-1) than daptomycin or fosfomycin alone. Daptomycin alone (16×MIC) showed anti-biofilm activities against the mature biofilms and bactericidal activities on the adherent cells, while daptomycin combined with fosfomycin (16×MIC) demonstrated significantly more anti-biofilm activities than daptomycin or fosfomycin alone and effectively killed the adherent cells in the mature biofilms. The high concentration of daptomycin (512 mg l^-1 ) combined with fosfomycin indicated more bactericidal activities on the adherent cells and more anti-biofilm activities against the mature biofilms than daptomycin 64 mg l^-1 (16×MIC) combined with fosfomycin. The addition of rifampin increased the anti-biofilm and bactericidal activities of daptomycin against the mature biofilms and the adherent cells of two isolates, however, which was not observed in other isolates.

Conclusions: Daptomycin combined with fosfomycin demonstrated better effect on the planktonic and adherent linezolid-resistant isolates of E. faecalis than daptomycin or fosfomycin alone. The role of rifampin in the treatment of E. faecalis isolates is discrepant and needs more studies.