Podcasts 科学播客 | 「快速败血症检测能否实现血液感染的早期诊断？」

Nick Petrić Howe

First up this week, reporter Benjamin Thompson has been learning about a new way speed up the treatment of patients with a life-threatening blood infection…

首先，本周记者Benjamin Thompson了解到一种加快治疗患有危及生命的血液感染患者的新方法……

Benjamin Thompson

Sepsis is a serious condition, where the body’s own immune system essentially goes into hyper-drive, damaging organs, potentially leading to death. It’s incredibly common, affecting tens of millions of people each year, and is a leading cause of morality around the world, but can be really difficult for clinicians to pick up.

败血症是一种非常严重的疾病，患者的免疫系统会进入过度反应状态而攻击自身器官，从而导致死亡。这种疾病非常普遍，每年影响数千万患者，是全球死亡的主要原因之一，但临床医生却很难及时识别。

Ron Daniels

Sepsis is a really hard condition to recognise and diagnose.

败血症确实很难识别和诊断。

Benjamin Thompson

This is Ron Daniels, an intensive care doctor and joint-CEO of the charity the UK Sepsis Trust.

这是Ron Daniels，一名重症监护医生，也是英国败血症信托基金会的联合首席执行官。

Ron Daniels

It can affect people of any age. It can arise as a complication of any infection anywhere in the body, and people present in a myriad of different ways. Yes, there will be some people who present in obvious, threatened or actual multi-organ failure but for every one person like that, there will be a dozen people who present with a much more insidious onset.

败血症可以影响任何年龄段的人，可能作为身体任何部位感染的并发症出现，患者的表现形式也千差万别。是的，有些人会以明显的、多器官功能衰竭的形式出现，但除了这样表现明显的患者，还有更多患者的症状在开始时会表现隐匿。

Benjamin Thompson

And while some people may initially present with less serious symptoms, it often doesn’t take much time for them to get into trouble.

虽然有些患者最初的症状不太严重，但通常用不了多久，他们就会陷入危机。

Ron Daniels

And that's what we have to look out for. Now, there's very variable estimates around the impact of delays in recognising and treating sepsis, and the estimates for each hour's delay range from about a 1% increase in mortality to at the greatest end, an 8% increase in mortality, and the true impact is likely to be somewhere in the middle. So this is a medical emergency. Yes, it's insidious, but that doesn't mean we don't have to act quickly.

这是我们需要警惕的地方。关于识别和治疗败血症的延误所带来的影响，各方估计值各不相同。每延误一小时，死亡率可能会增加1%-8%。所以这是一个医疗紧急情况，虽然它表现得隐匿，但并不意味着我们可以拖延治疗。

Benjamin Thompson

And part of acting quickly means getting the right treatment. While sepsis has many causes, one of the leading ones is bacteraemia — a bacterial infection of the blood — typically, treatment involves the rapid use of broad-spectrum antibiotics — these are vital, generalist drugs that don’t target a specific bacterial species — and they’re used to try and get on top of an infection, while doctors try to figure out what it is. But extended use of these drugs can increase the chances of resistance against them developing, they can have side effects, and they might just not be the most effective antibiotic available. Ideally clinicians want to limit the use of these broad-spectrum antibiotics and quickly move a patient onto narrow-spectrum antibiotics, but working out which ones are effective can, in many cases, take days, increasing the risks of adverse side effects, and potentially death. But this week, a team has designed a new way that could, if fully realised, drastically reduce the time it takes to identify the species of bacteria involved in an infection, and the antibiotics they are sensitive to.

快速行动的一部分就是提供正确的治疗。尽管败血症有多种原因，但其中一个主要原因是菌血症——即血液中的细菌感染。通常的治疗方法是快速使用广谱抗生素——这些是非特异性针对某种细菌的关键药物，目的是在医生弄清感染原因之前，尽早控制住感染。然而，长期使用这些药物可能增加抗药性的风险，还可能导致副作用，并且这些药物也许不是最有效的选择。理想情况下，临床医生希望尽早停止使用广谱抗生素，转而使用针对性的抗生素，但确定哪种抗生素有效通常需要几天的时间，这增加了副作用和死亡的风险。本周，一个研究团队设计出一种新方法，假如全面实现的话，可能会极大缩短识别感染细菌种类及提高抗生素敏感性的时间。

Sunghoon Kwon

Like 30 to 50 hour less than the conventional.

比传统方法快30到50个小时。

Benjamin Thompson

This is Sunghoon Kwon, from Seoul National University in Korea, one of the research team behind the new work. Sunghoon has been working for years to develop ways for clinicians to quickly diagnose whether someone has a bacterial blood infection and what’s causing it. The conventional way to do this takes so long because while a patient’s blood sample can contain millions upon millions of red and white blood cells, at the early stage of an infection it might have fewer than 100 bacteria. Not enough to run tests on. So the first step is to increase this number.

这是来自韩国首尔国立大学的Sunghoon Kwon，他是这项新研究的成员之一。Sunghoon多年来一直致力于为临床医生开发快速诊断细菌性血液感染病因的方法。传统的诊断方式耗时很长，因为虽然患者的血液样本中可能含有数百万个红细胞和白细胞，但在感染早期可能仅有不到100个细菌，数量不足以进行测试，所以第一步是增加这些细菌的数量。

Sunghoon Kwon

We put this blood into media, where bacteria can help to grow, and then, you know, we raise the temperature for like at least more than 10 to 24 hour.

我们将血液放入培养基中，让细菌在其中生长，然后我们将温度提高，通常至少需要10到24小时。

Benjamin Thompson

This growing step, known as blood culturing, is important because if nothing grows, the patient’s condition is not bacterially based. If it does though, there are more steps to come. A second pure culture step is required to remove all the blood cells, before the bacteria can be identified, and an antibiotic susceptibility test, or AST, can be done to see which drugs work. And together all this takes time.

这一生长步骤，称为血培养，它是非常重要的一步。如果没有细菌生长，意味着患者的感染不是由细菌引起的。但如果确实有生长，还需要进行下一步操作。第二步是进行纯培养，以去除所有的血细胞，随后才可以鉴定细菌并进行抗生素敏感性测试（AST），看看细菌对哪些药物有效，而这一整个过程都需要时间。

Sunghoon Kwon

So it takes, like, a three, four days from the blood draw to get the optimal antibiotic result.

从抽取血样到获得最优抗生素结果，通常需要三到四天。

Benjamin Thompson

So to help get survival rates up, researchers have been working to get this analysis time down. Some rapid antibiotic susceptibility tests — known as rapid ASTs — do exist, and Sunghoon has been involved in commercialising some of them. Rapid ASTs work in different ways, but can save about a day by doing away with the pure culture step. However, they still require the initial blood culture stage. In this work, Sunghoon and his colleagues have developed what they call an Ultra-rapid AST that can do away with this blood culture step as well, and they estimate it could produce results in less than a day. So how does it work? Well remember how those initial blood samples taken from patients could have an incredibly low number of bacteria, well, this method scoops them all up.

为了提高存活率，研究人员一直在努力缩短这一分析时间。现有的一些快速抗生素敏感性测试（即快速AST）可以省略纯培养步骤，从而节省约一天的时间。然而，它们仍然需要初步的血培养过程。在这项研究中，Sunghoon及其同事开发了一种超快速AST，能够省去血培养步骤，他们估计这一方法可以在一天之内得到结果。那么它是如何运作的呢？我们知道患者最初的血液样本中可能含有非常少量的细菌，而这种方法可以将它们全部捕获起来。

Sunghoon Kwon

The principle is simple. We have a little magnetic nanoparticle in the surface of the magnetic nanoparticle, we coat in a peptide that can capture the bacteria.

原理很简单。我们有一种涂有肽的磁性纳米颗粒，这些肽可以捕捉细菌。

Benjamin Thompson

These peptides stick to a wide range of pathogenic bacteria. Once attached, a magnet can be used to separate them out from all the blood cells, a process that takes around an hour, doing away with the need for a lengthy blood culture. The purified bacteria are then used for a genome-based species identification technique, or grown in culture for a few hours. This increases their numbers and allows them to be placed in essentially tiny petri dishes on a custom-made growth plate designed to rapidly test their sensitivity to different drugs.

这些肽能够粘附在多种致病细菌上。一旦粘附后，可以用磁铁将细菌从血细胞中分离出来，这一过程大约需要一个小时，省去了漫长的血培养步骤。纯化后的细菌可以用于基于基因组的物种鉴定技术，或者在培养基中生长几个小时。这会增加它们的数量，并使其可以放入专门设计的培养板中，快速测试其对不同药物的敏感性。

Sunghoon Kwon

This bacteria goes into many different chamber with many different antibiotics in different concentrations, and then we image them. So we look at the bacterial growth pattern for a few hours to know this AST result faster.

这些细菌被放入含有不同浓度抗生素的多个小室中，随后我们进行成像。通过观察几个小时内的细菌生长模式，我们可以更快地得到AST结果。

Benjamin Thompson

In the lab, the team’s method showed good results at assessing antibiotic sensitivity compared to conventional testing. The next step was to measure the accuracy of their approach in a clinical setting, so they enrolled 190 patients in Seoul National University Hospital who were suspected of having a blood infection.

在实验室中，该团队的方法在评估抗生素敏感性方面表现出色，结果与传统测试方法相当。下一步是测量该方法在临床环境中的准确性，因此他们在首尔国立大学医院招募了190名疑似血液感染的患者进行研究。

Sunghoon Kwon

So basically, we take out the patient blood, the one bottle goes to the conventional workflow, and the other bottle, you know, goes to our workflow, and we compared it.

我们抽取患者的血液样本，一瓶按照传统流程操作，另一瓶按照我们的流程操作，然后我们进行比较。

Benjamin Thompson

About 10% of those involved tested positive for an infection, so the team looked to see how their method stacked up in terms of species identification. They also tested their antibiotic sensitivity assay on six patient-derived bacterial strains.

大约10%的患者检测结果呈阳性，因此团队查看了他们的方法在物种鉴定中的表现。他们还对六株患者来源的细菌进行抗生素敏感性测试。

Sunghoon Kwon

So, you know, we got 100% accuracy on ID result. For the, you know, antibiotic result. We got, you know, more than 90% accuracy.

我们的物种鉴定结果达到了100%的准确率，而抗生素测试结果的准确率超过了90%。

Benjamin Thompson

Sunghoon estimates that if their method is perfected, antibiotic sensitivity tests could be turned around in less than a day from initial blood taking. Ron Daniels, the intensive care doctor you heard at the start, was impressed.

Sunghoon估计，如果他们的方法得以完善，从抽取血样到得到抗生素敏感性测试结果的时间可以缩短到不到一天。开篇提到的重症监护医生Ron Daniels对此印象深刻。

Ron Daniels

I think the most important thing about this particular technology is it's much more rapid. It can eliminate steps that many other technologies necessitate. So it improves processing time, it might, in time, pave the way to bring the technology closer to the patient. It's much more sensitive in terms of genetic identification of the bug it can be 1000 times more sensitive than other methods that don't rely on a pre culture of blood. So yes, it's one of a number of technologies in this space that are emerging into the marketplace, but it is one of the more exciting ones.

我认为这项技术的最大亮点在于它速度更快，消除了许多其他技术所需的步骤。它不仅缩短了处理时间，还可能为将该技术应用于患者铺平道路。它在基因鉴定细菌方面的敏感度要高得多，可能比不依赖血液预培养的其他方法敏感1000倍。因此，虽然这是市场上正在涌现的众多技术之一，但它无疑是其中更令人兴奋的一个。

Benjamin Thompson

Ron says that this rapid speed could mean that his patients might at most need two doses of broad-spectrum antibiotics before being placed on a targeted narrow-spectrum one, which has numerous benefits to patient outcomes. He also says that preventing the overuse of broad-spectrum antibiotics should help protect these drugs from the threat of resistance. However, Ron highlights something that all emerging antibiotic sensitivity tests face: fitting them to workflows.

Ron提到，这种快速意味着他的患者可能最多只需要两剂广谱抗生素，随后就可以转为针对性的窄谱抗生素，这对患者的治疗效果有诸多好处。他还指出，避免过度使用广谱抗生素有助于防止抗药性的产生。然而，Ron强调了所有新兴的抗生素敏感性测试都面临的一个挑战：如何将它们融入现有的临床工作流程。

Ron Daniels

The technology around diagnostics is evolving at an infinitely greater rate than our ability to integrate it into clinical systems, and therein lies the knowledge transfer gap. We've got to get a lot better at building this technology into clinical systems.

诊断技术的发展速度远远超过了我们将其整合到临床系统中的能力，这就是我们面临的知识转化鸿沟。我们必须大大提升将这些技术融入临床系统的能力。

Benjamin Thompson

For Ron, having a rapid, or ultra-rapid, test is one thing, but if it takes a day for a sample to get to the testing facilities, and the results take a further day to get into his hands, any benefits of speed are lost, so he says that figuring out the best way to get systems working together as efficiently as possible is critical for patient care. Sunghoon is acutely aware of this too and knows that working with clinicians and hospitals to streamline processes is key for technologies like this to be a success. And these are hurdles that will need to be overcome. But there are others too. At the moment this method has many manual steps — Sunghoon wants to work to combine and automate it all into a single device and if it passes the regulatory tests, it could be used in the not too distant future.

对于Ron来说，拥有一个快速或超快速的测试是一回事，但如果样本需要一天时间才能送到检测机构，结果再花一天时间到达他的手中，那么任何速度优势都会丧失。因此，他认为，找到最佳方法来使系统高效协作对于患者护理至关重要。Sunghoon对此也非常清楚，他知道与临床医生和医院合作，简化流程是使这类技术成功的关键。这是需要克服的障碍之一，但还有其他挑战。目前，这种方法还涉及许多手动步骤——Sunghoon希望将这些步骤整合并自动化为一个设备。如果能够通过监管测试，这项技术可能将会在不远的未来投入使用。

Sunghoon Kwon

I think that this technology can be in one box within three years, and then one more year will be needed for regulatory so if you have enough funding, then you know, within four years, it can be in the clinic.

我认为这项技术可以在三年内实现设备化，接下来的一年将用于监管审批。如果资金充足的话，四年内这项技术就可以应用于临床。

Benjamin Thompson

And if it gets there it could help improve the lives of patients with sepsis, their loved ones, and their doctors.

如果这一技术得到推广，将有助于改善败血症患者、他们家属以及医生的生活质量。

Ron Daniels

So for the individual patient, having this rapid diagnosis means that they and their families they might be unconscious, so their families perhaps can have confidence that we now have the information. We know what the bug is, we know what it's sensitive to. We're now delivering exactly the right therapy that's going to treat them whilst minimizing the unintended consequence of treating them. But I think there's another aspect. There's always health professional anxiety and scepticism around any missive that says we've got to treat something rapidly using a potentially dangerous agent. If the health profession has confidence that we have technologies like this that guide us to deliver the right therapy properly, it will make improvement programs for sepsis much more embraced and much more effective.

对于每个患者而言，快速诊断意味着他们及其家属（患者可能处于昏迷状态，因此更多是家属）可以确信我们已经掌握了所有信息。我们知道是什么细菌感染，知道它对什么药物敏感，现在正在提供正确的治疗，既能有效治病，又能最大限度减少治疗过程中的不良影响。但我认为还有另一个重要方面。医疗专业人员往往对要求快速使用潜在危险药物的指示感到焦虑和怀疑。然而，如果医疗团队确信我们拥有这样的技术，能够准确指导他们提供合适的治疗，那么败血症的改进项目将更容易被接受，且效果会更加显著。

Nick Petrić Howe

That was Ron Daniels from the UK Sepsis Trust. You also heard from Sunghoon Kwon from Seoul National University in Korea. To read Sunghoon’s paper look for a link in the show notes.

以上是来自英国败血症信托基金会的Ron Daniels的讲话。您还听到了来自韩国首尔国立大学的Sunghoon Kwon的分享。要阅读Sunghoon的论文，请查看节目笔记中的链接。