Daptomycin-nonsusceptible
vancomycin-resistant Enterococcus faecium (VRE) strains are a formidable emerging threat to patients with comorbidities, leaving few therapeutic options in cases of severe invasive
infections. Using a previously characterized isogenic pair of VRE strains from the same patient differing in their
daptomycin susceptibilities (Etest MICs of 0.38 mg/liter and 10 mg/liter), we examined the effect of
ceftaroline,
ceftriaxone, and
ampicillin on membrane fluidity and susceptibility of VRE to surface binding and killing by
daptomycin and human
cathelicidin antimicrobial peptide LL37. Synergy was noted in vitro between
daptomycin,
ampicillin, and
ceftaroline for the
daptomycin-susceptible VRE strain, but only
ceftaroline showed synergy against the
daptomycin-nonsusceptible VRE strain (∼2 log10 CFU reduction at 24 h).
Ceftaroline cotreatment increased
daptomycin surface binding with an associated increase in membrane fluidity and an increase in the net negative surface charge of the bacteria as evidenced by increased poly-
l-lysine binding. Consistent with the observed biophysical changes,
ceftaroline resulted in increased binding and killing of
daptomycin-nonsusceptible VRE by human
cathelicidin LL37. Using a pair of
daptomycin-susceptible/nonsusceptible VRE strains, we noted that VRE is
ceftaroline resistant, yet
ceftaroline confers significant effects on growth rate as well as biophysical changes on the cell surface of VRE that can potentiate the activity of
daptomycin and innate
cationic host defense peptides, such as
cathelicidin. Although limited to just 2 strains, these finding suggest that additional in vivo and in vitro studies need to be done to explore the possibility of using
ceftaroline as adjunctive anti-VRE
therapy.