Time to reappraise the antibiotic treatment for methicillin-susceptible Staphylococcus aureus infective endocarditis: data from the experimental model.

Abstract

BACKGROUND Traditional treatment of methicillin-susceptible Staphylococcus aureus (MSSA) native valve endocarditis is based on cloxacillin/cefazolin monotherapy. Antibiotics with high activity against MSSA such as ceftaroline and daptomycin have been marketed last years, but there are no clinical trials evaluating them as monotherapy or combination therapy in patients with MSSA endocarditis. OBJECTIVES To compare the efficacy of cloxacillin, ceftaroline and daptomycin monotherapies and daptomycin combinations with beta-lactams in a rabbit model of MSSA endocarditis. METHODS Endocarditis was induced in rabbits using two strains of MSSA. After 24h of infection, they received human-like doses of cloxacillin, ceftaroline or daptomycin or combinations of daptomycin plus either cloxacillin or ceftaroline. Isolates recovered from vegetation, spleen and kidney were retested for daptomycin non-susceptibility (DNS) post-treatment. RESULTS MSSA vancomycin MIC did not influence the efficacy of any antibiotic treatment. Cloxacillin, ceftaroline and daptomycin had similar activity (25-50%) in sterilizing vegetations. However, 13% of rabbits treated with daptomycin developed DNS. The addition of daptomycin to cloxacillin or ceftaroline was synergistic and bactericidal, showing significantly more activity and higher rates of sterile vegetations (≥90%) than any monotherapy Combinations also showed better activity in spleens and kidneys compared with daptomycin monotherapy and prevented the development of DNS in all tissues. There were no differences between the two daptomycin combinations. CONCLUSIONS In the MSSA experimental endocarditis model, daptomycin combinations with beta-lactams had significantly better activity than either their monotherapies in sterilizing valve vegetations and preventing DNS development. These findings support their use in clinical practice and to perform clinical trials.