We studied the prevention of experimental aortic
endocarditis caused by a
beta-lactamase-producing,
aminoglycoside-resistant strain of Enterococcus faecalis (HH22) in 146 catheterized rabbits. Both
vancomycin and
ampicillin-sulbactam readily killed this resistant enterococcus strain in vitro. At a challenge inoculum of approximately 10(9) CFU,
vancomycin (40 mg/kg intravenously [i.v.]),
ampicillin (40 mg/kg i.v.), or a combination of
ampicillin plus a
beta-lactamase inhibitor,
sulbactam (20 mg/kg, i.v.), did not prevent the development of
endocarditis in any of the animals, although mean intravegetation bacterial densities were significantly lower in animals that received
vancomycin than they were in animals that received other
therapies (P less than 0.001). At a challenge inoculum of 10(6) CFU,
vancomycin was 100% effective in preventing enterococcal
endocarditis compared with
ampicillin (29%; P less than 0.00001) and
ampicillin-sulbactam (65%; P less than 0.01). Factors associated with the superior prophylactic efficacy of
vancomycin in this model included prolonged serum inhibitory activity and time above MICs. Factors not associated with the antienterococcal prophylactic efficacy of
vancomycin included the duration of the in vitro postantibiotic effect of the
drug and the magnitude of the ability of this
drug to enhance enterococcal in vitro opsonophagocytic killing by polymorphonuclear leukocytes. The superior prophylactic efficacy of
vancomycin in this
endocarditis model related to the superior pharmacokinetic profile of the
drug when it was given intermittently at dose intervals of every 6 h.