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泰国一家大学医院的耐万古霉素肠球菌感染:临床特征、治疗结果及协同效应

Vancomycin-resistant enterococcal infection in a Thai university hospital: clinical characteristics, treatment outcomes, and synergistic effect.

作者信息

Hemapanpairoa Jatapat, Changpradub Dhitiwat, Thunyaharn Sudaluck, Santimaleeworagun Wichai

机构信息

Department of Pharmacy Practice and Pharmaceutical Care, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand.

College of Pharmacotherapy Thailand, Nonthaburi 11000, Thailand.

出版信息

Infect Drug Resist. 2019 Jul 11;12:2049-2057. doi: 10.2147/IDR.S208298. eCollection 2019.

Abstract

PURPOSE

The incidence of infections with vancomycin-resistant enterococci (VRE) is increasing, with associated high mortality rates and limited therapeutic choices. We investigated the clinical characteristics and treatment outcomes of VRE infection and also determined the in vitro effect of monotherapy and combined antimicrobials against clinical VRE isolates.

PATIENTS AND METHODS

Clinical data and bacterial isolates obtained from patients with VRE infections between January 2014 and April 2018 at Phramongkutklao Hospital were reviewed. The clinical outcomes included in-hospital mortality, 30-day mortality, and microbiological eradication. Clonal relationships were assessed by random amplified polymorphic DNA analysis. In vitro activity of linezolid, tigecycline, fosfomycin, gentamicin, chloramphenicol, and ampicillin were determined by minimum inhibitory concentration (MIC) values. Tests of synergy of fosfomycin- or gentamicin-based combinations by the checkerboard method were reported with the fractional inhibitory concentration index or MIC reduction, respectively.

RESULTS

Among 26 cases of VRE infection, nosocomial and gastrointestinal infections were the most common. There were various treatment regimens, but linezolid-containing regimens were generally used. In-hospital and 30-day mortality were 73.1% and 57.7%, respectively. Higher mortality was significantly associated with illness severity. The VRE isolates tested were universally susceptible to linezolid and tigecycline. A synergistic or additive effect was observed for fosfomycin combined with linezolid (100%) and with tigecycline (83.3%). Fourfold or greater MIC reduction was observed for linezolid or fosfomycin plus gentamicin at concentrations 1 (58.3%, 62.5%), 2 (83.3%, 62.5%), and 4 μg/mL (91.6%, 62.5%).

CONCLUSION

In-hospital mortality among patients with VRE infection was high. Linezolid remains a treatment of choice. However, combination therapy such as linezolid plus fosfomycin and linezolid plus gentamicin should be considered in cases of serious infection.

摘要

目的

耐万古霉素肠球菌(VRE)感染的发生率正在上升,伴有高死亡率且治疗选择有限。我们调查了VRE感染的临床特征和治疗结果,并确定了单一疗法和联合抗菌药物对临床VRE分离株的体外作用。

患者与方法

回顾了2014年1月至2018年4月在佛统皇家医院从VRE感染患者获得的临床数据和细菌分离株。临床结果包括院内死亡率、30天死亡率和微生物清除情况。通过随机扩增多态性DNA分析评估克隆关系。通过最低抑菌浓度(MIC)值测定利奈唑胺、替加环素、磷霉素、庆大霉素、氯霉素和氨苄西林的体外活性。分别用分数抑菌浓度指数或MIC降低报告棋盘法检测磷霉素或庆大霉素联合用药的协同作用。

结果

在26例VRE感染病例中,医院感染和胃肠道感染最为常见。有多种治疗方案,但一般使用含利奈唑胺的方案。院内死亡率和30天死亡率分别为73.1%和57.7%。较高的死亡率与疾病严重程度显著相关。所检测的VRE分离株对利奈唑胺和替加环素普遍敏感。磷霉素与利奈唑胺(100%)和替加环素(83.3%)联合观察到协同或相加作用。利奈唑胺或磷霉素加庆大霉素在浓度1(58.3%,62.5%)、2(83.3%,62.5%)和4μg/mL(91.6%,62.5%)时观察到四倍或更大的MIC降低。

结论

VRE感染患者的院内死亡率很高。利奈唑胺仍然是首选治疗药物。然而,在严重感染的情况下,应考虑联合治疗,如利奈唑胺加磷霉素和利奈唑胺加庆大霉素。

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Linezolid and Vancomycin Resistant Enterococci: A Therapeutic Problem.耐利奈唑胺和万古霉素的肠球菌:一个治疗难题。
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