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用于金黄色葡萄球菌鼻腔去定植的抗菌化合物的细胞内活性。

Intracellular activity of antimicrobial compounds used for Staphylococcus aureus nasal decolonization.

机构信息

Group for Mucosal Immunity and Pathogen Agents (GIMAP), EA 3064, University of Lyon, St-Etienne, France.

Laboratory of Infectious Agents and Hygiene, University Hospital of St-Etienne, St-Etienne cedex 02, France.

出版信息

J Antimicrob Chemother. 2018 Nov 1;73(11):3044-3048. doi: 10.1093/jac/dky318.

Abstract

BACKGROUND

Staphylococcus aureus is able to invade mammalian cells during infection and was recently observed inside nasal mucosa of healthy carriers.

OBJECTIVES

To determine the intracellular activity of antimicrobial compounds used for decolonization procedures using a cell model mimicking S. aureus nasal epithelium invasion.

PATIENTS AND METHODS

HaCaT cells and human nasal epithelial cells (HNECs) recovered from nasal swabs of S. aureus carriers were visualized by confocal laser scanning microscopy to detect intracellular S. aureus cells. An HaCaT cell model, mimicking S. aureus internalization observed ex vivo in HNECs, was used to assess the intracellular activity against S. aureus of 21 antimicrobial compounds used for nasal decolonization, including mupirocin and chlorhexidine.

RESULTS

HaCaT cells and HNECs were found to internalize S. aureus with the same focal pattern. Most antimicrobial compounds tested on HaCaT cells were shown to have weak activity against intracellular S. aureus. Some systemic antimicrobials, including fusidic acid, clindamycin, linezolid, minocycline, ciprofloxacin, moxifloxacin, rifampicin and levofloxacin, reduced S. aureus intracellular loads by 0.43-1.66 log cfu/106 cells compared with the control (P < 0.001). By contrast, mupirocin and chlorhexidine reduced the S. aureus intracellular load by 0.19 and 0.23 log cfu/106 cells, respectively.

CONCLUSIONS

These data indicate that most of the antimicrobial compounds used for nasal decolonization, including mupirocin and chlorhexidine, exhibit weak activity against intracellular S. aureus using the HaCaT cell model. This work emphasizes the need to better understand the role of the S. aureus intracellular reservoir during nasal colonization in order to improve decolonization procedures.

摘要

背景

金黄色葡萄球菌在感染过程中能够侵入哺乳动物细胞,最近在健康携带者的鼻腔黏膜中也观察到了这种现象。

目的

使用模拟金黄色葡萄球菌鼻腔上皮细胞侵袭的细胞模型,确定用于去定植程序的抗菌化合物的细胞内活性。

患者和方法

通过共聚焦激光扫描显微镜观察从金黄色葡萄球菌携带者的鼻腔拭子中回收的 HaCaT 细胞和人鼻腔上皮细胞 (HNEC),以检测细胞内金黄色葡萄球菌细胞。使用 HaCaT 细胞模型模拟 HNEC 中观察到的金黄色葡萄球菌内化,评估 21 种用于鼻腔去定植的抗菌化合物对金黄色葡萄球菌的细胞内活性,包括莫匹罗星和洗必泰。

结果

发现 HaCaT 细胞和 HNEC 以相同的焦点模式内化金黄色葡萄球菌。在 HaCaT 细胞上测试的大多数抗菌化合物对细胞内金黄色葡萄球菌的活性较弱。一些全身抗菌药物,包括夫西地酸、克林霉素、利奈唑胺、米诺环素、环丙沙星、莫西沙星、利福平、左氧氟沙星,与对照组相比,减少了 0.43-1.66 对数金黄色葡萄球菌细胞内负荷(P<0.001)。相比之下,莫匹罗星和洗必泰分别减少了 0.19 和 0.23 对数金黄色葡萄球菌细胞内负荷。

结论

这些数据表明,使用 HaCaT 细胞模型,大多数用于鼻腔去定植的抗菌化合物,包括莫匹罗星和洗必泰,对细胞内金黄色葡萄球菌的活性较弱。这项工作强调了需要更好地了解金黄色葡萄球菌在鼻腔定植期间细胞内储库的作用,以改善去定植程序。

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