Climo M W, Patron R L, Goldstein B P, Archer G L
Department of Internal Medicine, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, Virginia, USA.
Antimicrob Agents Chemother. 1998 Jun;42(6):1355-60. doi: 10.1128/AAC.42.6.1355.
The emergence of clinical isolates of methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin has prompted a search for new and novel therapeutic agents active against S. aureus. Lysostaphin, a peptidase produced by Staphylococcus simulans, specifically cleaves the glycine-glycine bonds unique to the interpeptide cross-bridge of the S. aureus cell wall. The effectiveness of various regimens of dosing with intravenous lysostaphin was compared to that of vancomycin in the rabbit model of aortic valve endocarditis caused by a clinical methicillin-resistant S. aureus isolate. All animals were treated for a total of 3 days. The most active regimen, lysostaphin given three times daily, produced sterile vegetations in 10 of 11 treated rabbits, with a mean reduction in vegetation bacterial counts of 8.5 log10 CFU/g compared to the counts in the untreated controls. In contrast, vancomycin given twice daily sterilized no vegetations and reduced vegetation bacterial counts by only 4.8 log10 CFU/g. Lysostaphin given once daily was less effective, reducing mean vegetation bacterial counts by only 3.6 log10 CFU/g, but the combination of lysostaphin once daily and vancomycin twice daily reduced the mean vegetation bacterial density by 7.5 log10 CFU/g, a result that was significantly better than that for either regimen alone (P < 0.05). Lysostaphin was well tolerated by the rabbits, with no evidence of immunological reactions following up to 9 weeks of intravenous administration. We conclude that lysostaphin given alone or in combination with vancomycin is more effective in the treatment of experimental methicillin-resistant S. aureus aortic valve endocarditis than vancomycin alone.
对万古霉素敏感性降低的耐甲氧西林金黄色葡萄球菌临床分离株的出现，促使人们寻找对金黄色葡萄球菌有效的新型治疗药物。溶葡萄球菌酶是模仿葡萄球菌产生的一种肽酶，能特异性切割金黄色葡萄球菌细胞壁肽间交联桥特有的甘氨酸 - 甘氨酸键。在由临床耐甲氧西林金黄色葡萄球菌分离株引起的主动脉瓣心内膜炎兔模型中，比较了静脉注射溶葡萄球菌酶的不同给药方案与万古霉素的有效性。所有动物共治疗3天。最有效的方案是每日给药3次的溶葡萄球菌酶，在11只接受治疗的兔子中有10只产生了无菌赘生物，与未治疗的对照组相比，赘生物细菌计数平均降低了8.5 log10 CFU/g。相比之下，每日给药2次的万古霉素未能使任何赘生物无菌化，仅使赘生物细菌计数降低了4.8 log10 CFU/g。每日给药1次的溶葡萄球菌酶效果较差，仅使赘生物细菌计数平均降低了3.6 log10 CFU/g，但每日给药1次的溶葡萄球菌酶与每日给药2次的万古霉素联合使用，使赘生物细菌平均密度降低了7.5 log10 CFU/g，这一结果明显优于单独使用任何一种方案（P < 0.05）。兔子对溶葡萄球菌酶耐受性良好，静脉给药长达9周后没有免疫反应的迹象。我们得出结论，单独使用溶葡萄球菌酶或与万古霉素联合使用，在治疗实验性耐甲氧西林金黄色葡萄球菌主动脉瓣心内膜炎方面比单独使用万古霉素更有效。
