Time to Reappraise the Antibiotic Treatment for Methicillin-Susceptible Staphylococcus aureus Infective Endocarditis:...

Area of Science:

• Infectious Diseases
• Pharmacology
• Microbiology

Background:

• Traditional methicillin-susceptible Staphylococcus aureus (MSSA) native valve endocarditis treatment relies on cloxacillin/cefazolin monotherapy.
• Newer antibiotics like ceftaroline and daptomycin show high MSSA activity but lack clinical trials for endocarditis.
• Evaluating novel agents and combinations is crucial for improving MSSA endocarditis outcomes.

Purpose of the Study:

• To compare the efficacy of cloxacillin, ceftaroline, and daptomycin monotherapies.
• To evaluate daptomycin combined with beta-lactams against MSSA endocarditis.
• To assess the development of daptomycin non-susceptibility (DNS) post-treatment.

Main Methods:

• A rabbit model of MSSA native valve endocarditis was established.
• Rabbits received human-like doses of cloxacillin, ceftaroline, daptomycin, or daptomycin combinations with beta-lactams.
• Bacterial isolates from vegetations, spleen, and kidney were analyzed for DNS.

Main Results:

• Cloxacillin, ceftaroline, and daptomycin monotherapies showed similar vegetation sterilization rates (25-50%).
• Daptomycin monotherapy led to DNS in 13% of rabbits.
• Daptomycin combined with cloxacillin or ceftaroline demonstrated synergistic activity, achieving ≥90% sterile vegetations and preventing DNS.

Conclusions:

• Daptomycin combined with beta-lactams significantly outperforms monotherapies in sterilizing MSSA endocarditis vegetations.
• Combination therapy effectively prevents the emergence of daptomycin non-susceptibility.
• These findings support the clinical use and further investigation of daptomycin-beta-lactam combinations for MSSA endocarditis.