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一种高通量、微创、超声引导的小鼠模型,用于研究导管相关性尿路感染和器械附着。

A high throughput, minimally invasive, ultrasound guided model for the study of catheter associated urinary tract infections and device encrustation in mice.

机构信息

Stone Centre at Vancouver General Hospital, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada; Department of Urology, Johannes Gutenberg University, Mainz, Germany.

Stone Centre at Vancouver General Hospital, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

出版信息

J Urol. 2014 Dec;192(6):1856-63. doi: 10.1016/j.juro.2014.05.092. Epub 2014 May 24.

Abstract

PURPOSE

Catheter associated urinary tract infections are one of the most common health care associated infections. The condition is frequently complicated by encrustation, which blocks the catheter lumen. Preclinical research is limited by the lack of relevant high throughput and cost-effective animal models. Current models are restricted to female mice, associated with major transurethral loss of catheter materials during micturition, highly invasive and complex. We present an ultrasound guided, minimally invasive model that enables catheter associated urinary tract infection and catheter encrustation studies in each mouse gender.

MATERIALS AND METHODS

Catheter segments (4 mm) were implanted in murine bladders percutaneously in 15 males and 5 females, and transurethrally in 15 females using the Seldinger technique under ultrasound guidance. Proteus mirabilis was instilled intraluminally. Catheter encrustation was monitored by ultrasound. Bacteria were quantified in urine, and catheters and encrustation were analyzed on day 6 or 21.

RESULTS

Percutaneous and transurethral catheter implantations were performed in a mean ± SE 3.6 ± 0.8 vs 2.5 ± 0.5 minutes in all mice. Ultrasound confirmed that 100% and 66% of implanted catheters, respectively, remained indwelling during the study period. Catheter encrustation developed in P. mirabilis infected urine 48 hours after instillation and an increase with time was detected by ultrasound. Fourier transform spectroscopy of the encrustation confirmed a typical struvite spectrum. Control catheters remained sterile during 21 days.

CONCLUSIONS

Our minimally invasive, reproducible percutaneous technique is suitable for studying catheter associated urinary tract infection in each gender. Infecting urine with P. mirabilis generates a preclinical model of catheter encrustation within 3 days. The progression of encrustation can be monitored in vivo by ultrasound, making this image based model suitable for assessing novel antibacterial and anti-encrustation therapies.

摘要

目的

导管相关尿路感染是最常见的医院获得性感染之一。该病症常伴有结石形成,从而堵塞导管腔。由于缺乏相关的高通量和具有成本效益的动物模型,临床前研究受到限制。目前的模型仅限于雌性小鼠,在排尿过程中,导管材料会大量经尿道损失,具有较高的侵入性和复杂性。我们提出了一种超声引导的微创模型,可在雌雄小鼠中进行导管相关尿路感染和导管结石形成的研究。

材料和方法

经皮穿刺将导管段(4 毫米)植入 15 只雄性和 5 只雌性小鼠的膀胱中,经尿道植入 15 只雌性小鼠的膀胱中,均在超声引导下使用 Seldinger 技术。将奇异变形杆菌注入导管腔。通过超声监测导管结石形成。定量检测尿液中的细菌,并在第 6 天或第 21 天分析导管和结石。

结果

在所有小鼠中,经皮和经尿道导管植入的平均时间分别为 3.6±0.8 分钟和 2.5±0.5 分钟。超声证实,分别有 100%和 66%的植入导管在研究期间保持留置。在注入尿液后 48 小时,奇异变形杆菌感染尿液中形成了导管结石,并且通过超声检测到结石随时间的增加。结石的傅里叶变换光谱分析证实了典型的鸟粪石光谱。在 21 天内,对照导管保持无菌。

结论

我们的微创、可重复的经皮技术适用于研究雌雄两性的导管相关尿路感染。用奇异变形杆菌感染尿液可在 3 天内产生导管结石形成的临床前模型。通过超声可以在体内监测结石的形成,使这种基于图像的模型适用于评估新型抗菌和抗结石形成的治疗方法。

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