LYSOSTAPHIN TREATMENT OF EXPERIMENTAL METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS AORTIC-VALVE ENDOCARDITIS

The emergence of clinical isolates of methicillin-resistant Staphyloco ccus aureus with reduced susceptibility to vancomycin has prompted a s earch for new and novel therapeutic agents active against S, aureus. L ysostaphin, a peptidase produced by Staphylococcus simulans, specifica lly cleaves the glycine-glycine bonds unique to the interpeptide cross -bridge of the S, aureus cell wall. The effectiveness of various regim ens of dosing with intravenous lysostaphin was compared to that of van comycin in the rabbit model of aortic valve endocarditis caused by a c linical methicillin-resistant S, aureus isolate. All animals were trea ted for a total of 3 days. The most active regimen, lysostaphin given three times daily, produced sterile vegetations in 10 of 11 treated ra bbits, with a mean reduction in vegetation bacterial counts of 8.5 log (10) CFU/g compared to the counts in the untreated controls. In contra st, vancomycin given twice daily sterilized no vegetations and reduced vegetation bacterial counts by only 4.8 log(10) CFU/g, Lysostaphin gi ven once daily was less effective, reducing mean vegetation bacterial counts by only 3.6 log(10) CFU/g, but the combination of lysostaphin o nce daily and vancomycin twice daily reduced the mean vegetation bacte rial density by 7.5 log(10) CFU/g, a result that was significantly bet ter than that for either regimen alone (P < 0.05), Lysostaphin was wel l tolerated by the rabbits, with no evidence of immunological reaction s following up to 9 weeks of intravenous administration. We conclude t hat lysostaphin given alone or in combination with vancomycin is more effective in the treatment of experimental methicillin-resistant S, au reus aortic valve endocarditis than vancomycin alone.