Evaluation of treatment options for Enterococcus faecalis endocarditis by assessing synergistic and anti-biofilm effects

Enterococcus faecalis is increasingly found as the causative organism of infective endocarditis, an infection of the heart valves with mortality rates up to 30 %. Traditionally, antibiotic combination therapy has been used for treatment of E. faecalis endocarditis, but it is still not clear if and which combination therapy is truly superior to monotherapy. Further, the treatment-resistant nature of infective endocarditis strongly suggests the involvement of biofilms. The main aim of this thesis was therefore to compare the recommended but nephrotoxic standard gentamicin/ampicillin combination with the recently recommended alternative ceftriaxone/ampicillin and the novel possibly effective ceftaroline/ampicillin combination by evaluating their synergistic interactions against planktonic and biofilm-embedded enterococci. On biofilm level, no synergistic effects between neither a cephalosporin- nor aminoglycoside-based combination could be observed, since none of the antibiotic combinations succeeded in eradicating mature E. faecalis biofilms. However, in planktonic E. faecalis cells synergism could be detected for ceftriaxone/ampicillin both in vitro and in a larval model, while for ceftaroline/ampicillin synergism was only detected in vitro. Gentamicin/ampicillin showed no synergistic effects for both in vitro and in vivo synergy analysis. In conclusion, the choice of antibiotic combination or monotherapy for treatment of E. faecalis endocarditis should ideally be based on the maturity and progression of biofilm development. While patients with an acute bacteraemia may benefit from a synergistic antibiotic combination therapy, combination therapy does not seem to be superior to monotherapy for treatment of mature biofilms. The results of this thesis favour the replacement of gentamicin/ampicillin by a cephalosporin-based combination due to the lack of synergistic effects. However, novel cephalosporins, i.e. ceftaroline, do not seem to provide additional benefit.


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