**5.1. Empiric therapy for CNE**

For patients with acute clinical presentations of native valve endocarditis, according to the US guidelines, empiric coverage for *S. aureus*, β-hemolytic *Streptococci* and aerobic Gram-negative bacilli is provided. Such regimens should include vancomycin and cefepime at the beginning. For patients with a subacute presentation of native valve endocarditis, additional empirical coverage of viridans *Streptococci*, HACEK and *Enterococci* is added. Vancomycin and ampicillin-sulbactam is a suggested regimen. If blood cultures eventually become positive for a typical pathogen, empiric treatment can be tailored accordingly. For patients with early (<1 year) culture-negative prosthetic valve endocarditis, empiric coverage for *Staphylococci, Streptococci, Enterococci* and Gram-negative bacilli is appropriate. Vancomycin, rifampin, gentamicin and cefepime are offered as options. For late prosthetic valve endocarditis, antibiotic therapy to cover viridans *Streptococci, Staphylococci* and *Enterococci* such as vancomycin and ceftriaxone is suggested. Empiric antibiotics can be narrowed based on specific pathogens that are subsequently identified. Surgical source control and removal of infected devices are required more often with the pathogens associated with CNE.
