Comparison of methicillin, nafcillin, and oxacillin in therapy of Staphylococcus aureus endocarditis in rabbits.

Methicillin (M), nafcillin (N), and oxacillin (OX) (400 mg administered intramuscularly every 8 hours) were compared in the therapy of left-sided endocarditis in rabbits infected with two different strains of Staphylococcus aureus. The three antibiotics were equally effective in eliminating staphylococci from cardiac vegetations. N and OX were four to eight times as active against the staphylococci as M in broth but had equivalent activity in serum. The peak M and OX levels in serum were at least twice the peak N level, but the half-life of N in the serum (2.1 hours) was about three times that of M (0.6 hours) and twice that of OX (1.1 hours). Serum bactericidal activity tests demonstrated essentially equal activity with the three antibiotics 1 and 2 hours after injection; however, at 4 and 6 hours N had an advantage over M and OX. Therefore, despite clear differences in vitro activity, protein binding, and pharmacodynamics, M, N, and OX were equally effective in therapy of staphylcoccal endocarditis in rabbits.