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[多重耐药革兰氏阳性菌心内膜炎的治疗]

[Treatment of multiresistant Gram positive endocarditis].

作者信息

Utili R

机构信息

Unita di Medicina Infettivologica e dei Trapianti, Seconda Universita degli studi di Napoli, Ospedale Monaldi, Napoli, Italy.

出版信息

Infez Med. 2009 Jul;17 Suppl 3:13-24.

Abstract

Epidemiology of infectious endocarditis has changed in last decades, endocarditis associated to hospital practices, sustained by multiresistant pathogens being highly increased. In particular, methicillin-resistant staphylococci (MRSA), almost resistant to a number of other antimicrobial classes, often exhibit a reduced susceptibility to vancomycin (h-VISA) with MICs' values more e than 1 mg/l, leading to suppose a reduced therapeutic efficacy of this drug. Thirty-one percent of MRSA strains in the ICE study, which prospectively collected more than 5000 endocarditis, were h-VISA. Daptomycin shows a rapid bactericidal activity against both methicillin-susceptible staphylococcci (MSSA) and MRSA, included those strains with reduced susceptibility to vancomycin. Daptomycin shows a good therapeutic efficacy in staphylococcal endocarditis: MRSA 71%, MSSA 75%. These data suggest the use of daptomycin as initial therapy for treatment of staphylococcal endocarditis, independently from methcillin susceptibility. Some experimental data showed that daptomycin efficacy can diminish, if it is used as a rescue therapy after vancomycin failure. The thickness of bacterial cell-wall recognized in h-VISA strains can represent a physical and electrical barrier to reach both the vancomycin and daptomycin target site. However, the reduced efficacy of daptomycin following vancomycin exposure is an extremely rare event in the clinical practice. It is preferrable to use daptomycin as first line therapy, at a proper dosage. As far as endocarditis is concerned, recent data proved the excellent daptomycin tolerability, with dosages up to 8-10 mg/kg/die. During the treatment, CPK values must be always monitored. For endocarditis sustained by vancomycin-resistant enterococci, therapeutic choices are based on linezolid or ampicillin-ceftriaxone combination therapy. Daptomycin alone, or in association with gentamycin and rifampin, can represent a promising therapeutic alternative.

摘要

在过去几十年中,感染性心内膜炎的流行病学发生了变化,与医院诊疗操作相关的心内膜炎有所增加,其由多重耐药病原体所致。特别是耐甲氧西林葡萄球菌(MRSA),几乎对许多其他抗菌药物类别耐药,通常对万古霉素的敏感性降低(h-VISA),其最低抑菌浓度(MIC)值大于1mg/L,这导致推测该药物的治疗效果降低。在ICE研究中,前瞻性收集了5000多例心内膜炎病例,其中31%的MRSA菌株为h-VISA。达托霉素对甲氧西林敏感葡萄球菌(MSSA)和MRSA均显示出快速杀菌活性,包括那些对万古霉素敏感性降低的菌株。达托霉素在葡萄球菌性心内膜炎中显示出良好的治疗效果:MRSA为71%,MSSA为75%。这些数据表明,无论甲氧西林敏感性如何,达托霉素均可作为葡萄球菌性心内膜炎的初始治疗药物。一些实验数据表明,如果在万古霉素治疗失败后用作挽救治疗,达托霉素的疗效可能会降低。h-VISA菌株中细菌细胞壁的厚度可代表到达万古霉素和达托霉素靶点的物理和电屏障。然而,在临床实践中,万古霉素暴露后达托霉素疗效降低是极为罕见的事件。最好以适当剂量将达托霉素用作一线治疗。就心内膜炎而言,最近的数据证明达托霉素耐受性良好,剂量高达8-10mg/kg/天。在治疗期间,必须始终监测肌酸磷酸激酶(CPK)值。对于由耐万古霉素肠球菌引起的心内膜炎,治疗选择基于利奈唑胺或氨苄西林-头孢曲松联合治疗。单独使用达托霉素,或与庆大霉素和利福平联合使用,可能是一种有前景的治疗选择。

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