The number of published cases of vancomycin-resistant E faecium IE treated with daptomycin is extremely small, so management conclusions are difficult to define, and the success rate has varied among reported cases. Levine and reported daptomycin cure in 6 of 9 patients with E faecium IE; both daptomycin-treated patients with E faecium IE reported by Segreti et al209 died. Multiple other case reports describe daptomycin failures, some as a result of emergence of daptomycin-resistance during treatment.210,211 Other inves- tigators have suggested that higher doses of daptomycin ); daptomycin combined with gentamicin, ampicillin, ceftaroline, rifampin, or tigecycline; or various combinations of these should be used instead of daptomycin A number of in vitro evaluations214 216 sug- gested that ampicillin and ceftaroline in combination with daptomycin demonstrate the greatest synergistic activity com- pared with other -lactam daptomycin combinations. Mave et al203 compared daptomycin with linezolid for vancomycin-resistant Enterococcus bacteremia. Five patients had E faecium IE; 1 of 2 daptomycin-treated patients and 2 of 3 linezolid-treated patients survived. The number of cases of vancomycin-resistant Enterococcus bacteremia was too small to draw significant conclusions about treatment response rates. In summary, there are insufficient data to recommend monotherapy with daptomycin for the treatment of multidrug- resistant enterococcal IE. If daptomycin therapy is selected, may be considered. Consideration may be given to combinations of therapy with daptomycin, including ampicillin or ceftaroline, particularly in patients infected with strains with relatively high MICs to daptomycin within the susceptible range (<4 g/mL). Other less active (in vitro) combinations with daptomycin include gentamicin, rifampin, or tigecycline. Table 14. 