Lysostaphin Treatment of Experimental Aortic Valve Endocarditis Caused by a Staphylococcus aureus Isolate with Reduced Susceptibility to Vancomycin

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Abstract
The rabbit model of endocarditis was used to test the effectiveness of vancomycin and two different lysostaphin dosing regimens for the treatment of infections caused by a Staphylococcus aureusstrain with reduced susceptibility to vancomycin (glycopeptide-intermediate susceptible S. aureus [GISA]). Vancomycin was ineffective, with no evidence of sterilization of aortic valve vegetations. However, rates of sterilization of aortic valve vegetations were significantly better for animals treated with either a single dose of lysostaphin (43%) or lysostaphin given twice daily for 3 days (83%) than for animals treated with vancomycin. Rabbits given a single dose of lysostaphin followed by a 3-day drug-free period had mean reductions in aortic valve vegetation bacterial counts of 7.27 and 6.63 log10 CFU/g compared with those for untreated control rabbits and the vancomycin-treated group, respectively. We conclude that lysostaphin is an effective alternative for the treatment of experimental aortic valve endocarditis caused by a clinical VISA strain.