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19F 磁共振成像评估全氟碳化合物在金黄色葡萄球菌感染模型中对抗生素治疗的反应。

19F magnetic resonance imaging of perfluorocarbons for the evaluation of response to antibiotic therapy in a Staphylococcus aureus infection model.

机构信息

Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany.

出版信息

PLoS One. 2013 May 28;8(5):e64440. doi: 10.1371/journal.pone.0064440. Print 2013.

DOI:10.1371/journal.pone.0064440
PMID:23724049
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3665837/
Abstract

BACKGROUND

The emergence of antibiotic resistant bacteria in recent decades has highlighted the importance of developing new drugs to treat infections. However, in addition to the design of new drugs, the development of accurate preclinical testing methods is essential. In vivo imaging technologies such as bioluminescence imaging (BLI) or magnetic resonance imaging (MRI) are promising approaches. In a previous study, we showed the effectiveness of (19)F MRI using perfluorocarbon (PFC) emulsions for detecting the site of Staphylococcus aureus infection. In the present follow-up study, we investigated the use of this method for in vivo visualization of the effects of antibiotic therapy.

METHODS/PRINCIPAL FINDINGS: Mice were infected with S. aureus Xen29 and treated with 0.9% NaCl solution, vancomycin or linezolid. Mock treatment led to the highest bioluminescence values during infection followed by vancomycin treatment. Counting the number of colony-forming units (cfu) at 7 days post-infection (p.i.) showed the highest bacterial burden for the mock group and the lowest for the linezolid group. Administration of PFCs at day 2 p.i. led to the accumulation of (19)F at the rim of the abscess in all mice (in the shape of a hollow sphere), and antibiotic treatment decreased the (19)F signal intensity and volume. Linezolid showed the strongest effect. The BLI, cfu, and MRI results were comparable.

CONCLUSIONS

(19)F-MRI with PFCs is an effective non-invasive method for assessing the effects of antibiotic therapy in vivo. This method does not depend on pathogen specific markers and can therefore be used to estimate the efficacy of antibacterial therapy against a broad range of clinically relevant pathogens, and to localize sites of infection.

摘要

背景

近几十年来,抗生素耐药菌的出现凸显了开发新药物治疗感染的重要性。然而,除了设计新药外,开发准确的临床前测试方法至关重要。活体成像技术,如生物发光成像(BLI)或磁共振成像(MRI),是很有前途的方法。在之前的一项研究中,我们展示了使用全氟碳(PFC)乳液进行(19)F MRI 检测金黄色葡萄球菌感染部位的有效性。在本后续研究中,我们研究了该方法在抗生素治疗的体内可视化中的应用。

方法/主要发现:小鼠感染金黄色葡萄球菌 Xen29 并用 0.9%NaCl 溶液、万古霉素或利奈唑胺治疗。模拟治疗导致感染期间的生物发光值最高,其次是万古霉素治疗。感染后 7 天(p.i.)时对集落形成单位(cfu)进行计数显示,模拟组的细菌负荷最高,利奈唑胺组最低。在第 2 天 p.i.时给予 PFC 导致(19)F 在脓肿边缘积聚(呈空心球体形状),抗生素治疗降低了(19)F 信号强度和体积。利奈唑胺的效果最强。BLI、cfu 和 MRI 结果相当。

结论

使用 PFC 的(19)F-MRI 是评估体内抗生素治疗效果的有效非侵入性方法。该方法不依赖于病原体特异性标志物,因此可用于估计针对广泛的临床相关病原体的抗菌治疗效果,并定位感染部位。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4117/3665837/50a25681a52b/pone.0064440.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4117/3665837/2c3375b21054/pone.0064440.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4117/3665837/ba068fad11c2/pone.0064440.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4117/3665837/1e5c4d00bfd8/pone.0064440.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4117/3665837/50a25681a52b/pone.0064440.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4117/3665837/2c3375b21054/pone.0064440.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4117/3665837/ba068fad11c2/pone.0064440.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4117/3665837/1e5c4d00bfd8/pone.0064440.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4117/3665837/50a25681a52b/pone.0064440.g004.jpg

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