There are no experimental studies regarding the prophylactic efficacy of
linezolid against
infective endocarditis. Nonbacterial thrombotic
endocarditis of the aortic valve was induced in rabbits by the insertion of a
polyethylene catheter. Twenty-four hours later, animals were randomly assigned to a control group, and groups receiving either
ampicillin (two doses of 40 mg/kg of
body weight each, given intravenously, 2 h apart) or
linezolid (a single per os dose of 75 mg/kg). The first dose of
ampicillin and the single dose of
linezolid were administered 0.5 and 1 h, respectively, prior to the intravenous inoculation of approximately 10(7) CFU of Streptococcus oralis or Enterococcus faecalis.
Linezolid peak levels in rabbit serum were similar to the peak serum levels in humans following a 600-mg oral dose of
linezolid.
Linezolid prevented
endocarditis in 87% of S. oralis-challenged rabbits (P < 0.001 versus controls; P = 0.026 versus
ampicillin). In rabbits challenged with E. faecalis,
linezolid prevented
endocarditis in 73% (P = 0.003 versus controls; P = 0.049 versus
ampicillin).
Ampicillin prevented
endocarditis due to S. oralis or due to E. faecalis in 47% (P = 0.005 versus controls) and in 30% (P = not significant versus controls) of the challenged animals, respectively. In conclusion,
linezolid was effective as prophylaxis against
endocarditis caused by a strain of S. oralis and to a lesser degree against that caused by a strain of E. faecalis. Its prophylactic efficacy was superior to that of
ampicillin.