在存在多种类型的抗生素的情况下，可以在许多类型的抗生素存在下生长的多药微生物，这是一个固执，持久和广泛的问题，尤其是在医院和疗养院等医疗保健环境中。在最好的情况下很难治疗，他们可以对使用它们使用的每种抗生素产生多种抗药性。有时，抗性机制甚至可能在特定的细菌中积累和巩固。更糟糕的是，他们可以从个体的消化道转移到环境，然后再回到新人的肠道，以分布在整个人群中。较高的风险较差，例如血液感染，败血症，甚至死亡。“患有症状感染的患者只是冰山一角，”埃默里医学院助理教授迈克尔·伍德沃斯（michael woodworth）说。“无声传输是一个问题。一个人可能根本没有症状，并将其传递给其他没有症状的人。在某人患有症状感染之前，这可能会发生在链条中的几个人中，这种感染更难以治疗抗生素。但是，现在是drs的新研究。伍德沃思（woodworth）和科琳·卡夫（colleen kraft）是病理学系和医学学院传染病学院教授，通过将微生物群从健康捐助者的粪便移植到肾脏移植受助人群中，通过将微生物群移植到一个特别容易发生的人群中，通过将微生物群从健康供体的粪便中移植到肾脏移植者中来减少多种药物的定殖。这项研究最近发表在科学转化医学上，灵感来自2013年早期发现，微生物群移植能够减少与单一耐药的微生物相关的医院感染，c。艰难梭菌。伍德沃思说，该试验是如此有效，“它已经停止了，因为继续治疗患有抗生素的患者是没有道德的，因为粪便菌群移植的疗效要高得多。”因为对c患者进行了研究。”。用粪便移植治疗的艰难梭也显示出其他生物的定殖降低，伍德沃思和卡夫特想知道是否可以将技术扩展到更广泛的微生物。从2018年开始，该团队开始从健康志愿者招募的现有粪便银行计划中汲取材料，对其进行过滤，将其悬挂在盐水中，并通过灌肠对参加埃默里大学医院和埃默里诊所的临床试验的肾脏移植患者进行管理。所有患者的病史至少是由多种耐药的生物引起的一种感染。基德尼移植患者之所以选择医疗保健系统中有许多接触，接受更多的抗生素，并承担更多抗生素，并且具有较高的多种药物生物体负担。它们也失去了更多，因为用于治疗它们的最新抗生素通常是肾毒性，可能会伤害其移植的肾脏。一组患者开始接受移植，然后如果在36天后仍然是耐药的生物阳性，则进行第二次移植。如果在观察期间仍然是正面的，则第二组在36天标记处进行了延迟的粪便移植。作为一个额外的对照，伍德沃思和牛aft研究了符合研究资格但没有接受粪便移植的第三组肾脏患者的感染数据。多药耐药生物的培养物比较对照组。在第36天，对照组中的每个人仍然是多种耐药的生物阳性，而只有三分之一的粪便菌群移植。在第36天之前，十名接受至少一项移植的参与者中有八名是负面的。在第36天接受所有移植的九名参与者中有8名是负面的。研究人员得出结论，移植的患者具有更快的耐药性生物体化，并且更长的时间延长多种药物抗药性组织感染的复发。研究人员使用强大的元基因组学工具，让他们同时研究整个微生物的dna，同时研究了哪些微生物在移植后患者中持续了哪些微生物。在三名患者中，研究人员发现移植前的抗性细菌被移植后的另一种菌株取代。知道这是如何发生的，这可能是开发基于微生物群的抗生素耐药性治疗的重要一步事实证明是一个挑战。研究人员不确定易感应变还是。multi-drug resistant microbesmicroorganisms that can grow in the presence of many types of antibioticsare a stubborn, persistent and widespread problem, especially in healthcare settings like hospitals and nursing homes. difficult to treat under the best of circumstances, they can acquire multiple kinds of resistance to every kind of antibiotic used against them. sometimes, resistance mechanisms may even accumulate and consolidate within a particular species of bacteria. worse, they can move from the digestive tract of individuals to the environment, then back to the human gut of new individuals to spread throughout populations.even though these individuals may not have symptoms, patients who are colonized with these multi-drug resistant microbes are at higher risk of worse outcomes such as bloodstream infections, sepsis, even death. “patients who have symptomatic infections are just the tip of the iceberg,” says michael woodworth, md, assistant professor in emory’s school of medicine. “silent transmission is a problem. one person may have no symptoms at all and pass it on to another person who has no symptoms either. this may happen across several people in a chain before someone has a symptomatic infection that is harder to treat with antibiotics.”the few existing treatments for reducing colonization of multi drug resistant organisms have had only limited effectiveness. now however, new research from drs. woodworth and colleen kraft, professor in the department of pathology and the school of medicine’s division of infectious diseases, has managed to reduce multi drug resistant colonization by transplanting microbiota from the stool of healthy donors into kidney transplant recipients, an especially vulnerable population. the study, published recently in science translational medicine, was inspired by earlier findings in 2013 that microbiota transplants managed to reduce a hospital infection associated with a single drug-resistant microbe, c. difficile.woodworth says the trial was so effective, “it was stopped early because it wasn’t thought to be ethical to continue to treat patients with antibiotics because the efficacy with fecal microbiota transplant was so much higher.”because studies of patients with c. difficile treated with fecal matter transplants have shown reduced colonization of other organisms as well, woodworth and kraft wondered whether it might be possible to extend the technique to a wider range of microorganisms. starting in 2018, the team began taking material from an existing fecal banking program recruited from healthy volunteers, filtering it, suspending it in saline and administering by enema it to kidney transplant patients participating in a clinical trial at emory university hospital and the emory clinic. all the patients had a history of at least one infection caused by a multi drug resistant organism.kidney transplant patients were chosen because they are have had many encounters in the healthcare system, receive more antibiotics and have a higher burden of multi drug resistant organisms. they also stand to lose more because the newest antibiotics used to treat them are often nephrotoxic and could injure their transplanted kidney. one group of patients started with a transplant, then got a second transplant if they were still drug resistant organism positive after 36 days. a second group got a delayed fecal transplant at the 36 day mark if they were still positive after an observation period. as an additional control, woodworth and kraft studied infection data in a third group of kidney patients who were eligible for the study but didn’t receive a fecal transplant.the researchers found the group treated with fecal microbiota transplants had a shorter time to negative stool culture for multidrug resistant organisms compared the control group. at day 36, everyone in the control group was still multi drug resistant organism positive vs only a third of the group treated with fecal microbiota transplants. eight of the ten participants who received at least one transplant were negative by day 36. eight out of nine who received all transplants were negative by day 36. the researchers concluded the patients with transplants had more rapid multi drug resistant organism decolonization and longer time to a recurrence of multi drug resistant organization infection.the investigators got a surprise when they used the powerful tools of metagenomics, letting them study dna from whole classes of microorganisms at the same time, to see which microbes persisted in their patients after the transplant. in three patients, the investigators found that a resistant strain of bacteria before the transplant was replaced by another strain of the same species after transplant.knowing how this happened could be an important step in developing a microbiota-based treatment for antibiotic resistance but investigating it turned out to be a challenge.the researchers weren’t sure whether the susceptible strains originated in the patients and expanded after transplant, were introduced by the transplant itself, acquired from the environment, or even represented a genetic change selected by the transplant. they couldn’t find the replacing strains in the transplant material or genetic changes within a single strain that might have led to the loss of drug resistance. finally, they concluded at least a subset of patients had two strains of e. coli with different levels of resistance to drugs and something about the transplant helped the susceptible strain outcompete the resistant strain. when they plated both strains in vitro on a culture medium, the susceptible strain outcompeted the resistant strain, further evidence that confirmed the metagenomic data that these strains were competing.woodworth says his team never expected to discover competition between the resistant and susceptible strains. “it was surprising to us that these bacteria are fighting each other in this way within human hosts,” he says. “and that there are co-occurring strains of different antibiotic susceptibilities that would have totally been missed by other methods.” they are still searching for a more complete explanation for the competitive process, which may exist between different species of microbes or even groups of species as well as between strains of a single species. ultimately, they hope to develop therapies that are more feasible than the fecal microbiota transplants used in their research.two new microbiota therapies against drug resistance were recently approved by the fda, rebyota and vowst. studies of these therapies have also suggested they can reduce colonization with antibiotic resistant bacteria but they have only been approved for preventing recurrent infection with a single microbe, c. difficile. woodworth’s lab is now trying to better understand the strains and genes likely to be most useful for a treatment to reduce colonization with multi drug resistant organisms. “its important to design these studies to look at not just the resistant bugs, but also the more susceptible ones,” he says. “so we can better understand the microecology of patients that are colonized. the takeaway for me as an infectious disease doctor is hope that we could develop new approaches for these patients who are colonized with antibiotic resistant bacteria beyond isolating them. we hope to help develop something beyond fecal matter transplantation to decolonize patients to prevent infection and transmission.” metagenomics refers to deep dna sequencing of whole communities of microbes. it allows us to understand the composition of these communities without culturing them and also allows us to track closely related strains in these communities over time. .亲，点击此处在线申请留学咨询服务和报名评估！我们将竭诚提供最佳评估服务！
