Optimising Vancomycin Dosing for C. difficile Infection (OVID-CDI)

难辨梭状芽胞杆菌引起患者肠道感染，导致腹泻。症状可从轻微到严重，每天腹泻10次以上，并可能危及生命。艰难梭菌只在肠道内引起感染，通常是由于服用治疗其他细菌感染的药物（抗生素）而扰乱了正常的有益细菌平衡。艰难梭菌感染（CDI）的患者通常是年老体弱的，特别是因为这些人最有可能接受过许多抗生素治疗。由于CDI是一种细菌感染，治疗需要服用更多的抗生素，这可能会进一步损害肠道中的有益细菌。然后，患者可能会出现另一种CDI感染，即复发性CDI，这增加了再次住院和死亡的机会。目前，最常用和推荐的治疗方案是一种名为万古霉素的抗生素。另一种选择是非达霉素，它不会像万古霉素那样减少有益细菌的数量，因此会导致更少的CDI复发病例，但它要贵得多，因此不常用。我们用于治疗CDI的万古霉素的用量很久以前就确定了，但没有经过任何具体的试验/实验来找出最佳用量。论文中的一些数据表明，艰难梭菌可以被远远低于我们目前使用的剂量杀死。因此，我们有可能使用更少量的万古霉素，仍然可以有效地治疗感染，但不会对有益细菌造成太多损害。从理论上讲，这将减少复发性CDI病例，这对患者和NHS都更好。更少的万古霉素也意味着CDI治疗对NHS和其他国家来说会更便宜。在利兹，我们开发了模拟正常有益肠道细菌种群的肠道实验室模型（来自健康志愿者的粪便样本）。这意味着我们可以看到药物如何影响肠道中的有益细菌，而无需对患者进行测试。我们想用这些肠道模型来看看低剂量的万古霉素是否仍然可以治疗CDI感染，同时不会对有益的肠道细菌造成如此大的损害。因此，我们也将能够检查低剂量的万古霉素是否可以减少CDI的复发。为了确定万古霉素的用量，我们将回顾所有目前发表的关于万古霉素的知识，然后将这些信息与精心设计的实验室实验相结合。这些实验将确定万古霉素杀死艰难梭菌的最低剂量，并将帮助我们确定在肠道模型中进行测试的最佳剂量。我们计划举办两场教育活动，与病人、公众、医护专业人士和业界代表互动；一个在研究开始时，一个在研究结束时。通过开发研究目标和结果的视觉解释，我们希望确保所有参与者都能轻松理解。这些单页信息传单也可以通过我们与各种患者参与组织（如C. Diff基金会）的联系分发。利兹大学还举办了一个名为“好奇”的年度公众参与活动，我们将参加并展示我们的研究结果。研究结果将在会议上提交给国际科学界，并通过在开放获取期刊上发表。该项目的最终目的是确定一种更好的、负担得起的万古霉素治疗方法，这种方法可能对患者有益，从而可以在未来的临床试验中进行测试。

The bacterium Clostridium difficile causes an infection in the bowel/guts of patients which results in diarrhoea. Symptoms can range from mild to severe with >10 episodes of diarrhoea per day, and can be life-threatening. C. difficile only causes an infection in guts where the normal balance of good bacteria has been disturbed, usually by taking drugs (antibiotics) for other bacterial infections. Often, patients with C. difficile infection (CDI) are elderly and frail, particularly as these people are the most likely to have received many antibiotics. Because CDI is a bacterial infection, the treatments involve taking even more antibiotics, which can further damage the good bacteria in the gut. Patients can then develop another CDI infection, known as recurrent CDI, which increases the chance of hospital readmission and dying. Currently, the most commonly used and recommended treatment option is an antibiotic called vancomycin. Another option, called fidaxomicin does not reduce the populations of good bacteria as much as vancomycin, and therefore leads to fewer cases of recurrent CDI, but it is much more expensive and so is not used as often. The amount of vancomycin we use to treat CDI was decided a long time ago, but not following any specific trials/experiments to find out the best amount to use. Some data available in papers suggest that the C. difficile bacteria can be killed by amounts far lower than those that we currently use. It is possible, therefore, that we can give a much smaller amount of vancomycin, still treat the infection effectively, but not damage the good bacteria as much. This would theoretically lead to fewer recurrent CDI cases, which is better for patients and the NHS. Less vancomycin would also mean that CDI treatments would be cheaper for the NHS and in other countries. In Leeds, we have developed laboratory models of the gut that mimic the populations of normal good gut bacteria (sourced from poo samples from healthy volunteers). This means we can see how drugs affect the good bacteria in our guts, without having to test patients. We would like to use these gut models to see if lower amounts of vancomycin can still treat the CDI infection, while not damaging the good gut bacteria so much. We will also be able to check whether lower amounts of vancomycin can lead to less CDI recurrence because of this. In order to decide the amounts of vancomycin to use, we will review all of the current published knowledge on vancomycin and then combine this information with carefully designed laboratory experiments. These experiments will determine the lowest amounts of vancomycin that will kill the C. difficile bacteria, and will help us determine the best doses to test in the gut models. We plan to engage with patients, the public, healthcare professionals and industry representatives by holding two educational events; one at study kick off and one at the end of the study. By developing visual interpretations of the study aims and outcomes, we hope to ensure that they can be easily understood by all who attend. These one page information leaflets can also be distributed via our connections with various patient engagement organisations, such as the C. Diff Foundation. The University of Leeds also hosts an annual public engagement event called Be Curious, which we will attend and present our study findings. Study results will be presented to the international scientific community at conferences and via publication in open access journals. The ultimate aim of this project is to identify a better, affordable vancomycin treatment that may be beneficial to patients, and so can be tested in a future clinical trial.