Reduced Vancomycin Susceptibility in an In Vitro Catheter-Related Biofilm Model Correlates with Poor Therapeutic Outcomes in Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus
Reduced Vancomycin Susceptibility in an In Vitro Catheter-Related Biofilm Model Correlates with Poor Therapeutic Outcomes in Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus
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DOI：
10.1128/aac.02073-12
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发表时间：
2013-03-01
影响因子：
4.9
通讯作者：
Xiong, Yan Q.
中科院分区：
文献类型：
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作者：
Abdelhady, Wessam;Bayer, Arnold S.;Xiong, Yan Q.
金黄色葡萄球菌是血管内感染的最常见原因，包括导管败血症和感染性心内膜炎（IE）。万古霉素（货车）是治疗耐甲氧西林链球菌的首选药物。金黄色葡萄球菌（MRSA）感染。然而，VAN敏感菌株引起的MRSA感染中货车治疗失败率高的报道越来越多。生物膜相关的MRSA感染特别容易导致临床抗生素治疗失败。本研究探讨了MRSA对体外生物膜中货车的敏感性与体内血管内感染中货车的不敏感性之间的潜在关系。使用先前在实验IE中针对货车响应性研究的10种“VAN敏感”MRSA血流分离株，我们研究了这种体内货车抗性的机制，包括：（i）货车与MRSA生物体的结合;（ii）货车对生物膜形成和生物膜组成的影响;（iii）体外导管相关生物膜模型中的货车功效;（iv）对细胞壁厚度的影响。作为一个组，先前在实验IE模型中被归类为货车无应答者（non-Rsp）的五种菌株在以下方面不同于五种应答者（Rsp）：较低的货车结合、增加的生物膜形成、在存在或不存在导管的情况下在生物膜内存在货车的情况下较高的存活率、以及在蛋白酶K处理后较大的生物膜减少。有趣的是，货车的亚MIC仅在非Rsp分离株中显著促进生物膜形成。所有MRSA菌株的细胞壁厚度相似。这些结果表明，诱导生物膜形成和降低货车在体外导管相关生物膜中的功效的亚致死货车水平可能导致由“VAN敏感”MRSA菌株引起的血管内感染的次优治疗结果。
Staphylococcus aureus is the most common cause of endovascular infections, including catheter sepsis and infective endocarditis (IE). Vancomycin (VAN) is the primary choice for treatment of methicillin-resistant S. aureus (MRSA) infections. However, high rates of VAN treatment failure in MRSA infections caused by VAN-susceptible strains have been increasingly reported. Biofilm-associated MRSA infections are especially prone to clinical antibiotic failure. The present studies examined potential relationships between MRSA susceptibility to VAN in biofilms in vitro and nonsusceptibility to VAN in endovascular infection in vivo. Using 10 "VAN-susceptible" MRSA bloodstream isolates previously investigated for VAN responsiveness in experimental IE, we studied the mechanism(s) of such in vivo VAN resistance, including: (i) VAN binding to MRSA organisms; (ii) the impact of VAN on biofilm formation and biofilm composition; (iii) VAN efficacy in an in vitro catheter-related biofilm model; (iv) effects on cell wall thickness. As a group, the five strains previously categorized as VAN nonresponders (non-Rsp) in the experimental IE model differed from the five responders (Rsp) in terms of lower VAN binding, increased biofilm formation, higher survival in the presence of VAN within biofilms in the presence or absence of catheters, and greater biofilm reduction upon proteinase K treatment. Interestingly, sub-MICs of VAN significantly promoted biofilm formation only in the non-Rsp isolates. Cell wall thickness was similar among all MRSA strains. These results suggest that sublethal VAN levels that induce biofilm formation and reduce efficacy of VAN in the in vitro catheter-associated biofilms may contribute to suboptimal treatment outcomes for endovascular infections caused by "VAN-susceptible" MRSA strains.