A platform for reduction of incidence of ventilator-associated pneumonia through modified PVC biomaterials

大约20年来，我们一直在调查重症监护病房(ICU)患者因肺部感染和肺炎而导致的高死亡率。手术后，病人通常会被送进ICU，在那里他们可以受到仔细的监测。这种额外的护理是必要的，因为患者可能是年迈、非常虚弱的人，或者需要特殊的设备来帮助他们康复。ICU医务人员面临的一个主要挑战是使患者免受感染。细菌是医院的一个问题，许多ICU患者死于肺炎。ICU的患者经常服用药物来削弱他们的免疫系统，例如，允许移植被身体接受而不是被排斥。不幸的是，这使得他们的身体非常容易受到感染。进一步的并发症是，患者经常有几根管子将他们的身体连接到专门的设备上。其中一个塑料管是气管内(ET)管，它被插入患者的气管，将人工呼吸机中的空气输送到肺部。不幸的是，细菌会被ET管的塑料吸引。细菌群落被称为生物膜，在管子的塑料表面覆盖一层粘液状的层，类似于牙齿上形成的细菌菌斑。由于生物膜位于ET管的内壁，以及保护细菌细胞的粘液状物质，因此用抗生素极难杀死生物膜。当通风的空气被泵入患者的ET管时，生物膜中生长的一些细菌从表面脱落并进入肺部。这可能会导致严重的肺炎病例。我们从在ICU死亡或康复的患者身上获得了ET管，并调查了有多少细菌附着在这些管上，以及附着在这些管上的细菌类型。这些研究使我们能够制定我们的研究计划，通过修改ET管的表面来防止细菌感染，这最终将减少在ICU中死亡的患者数量。我们仍将使用被称为季铵化合物或QAC的特殊类型的抗生素，但我们将不再以注射或片剂的形式给它们，而是将它们永久地附着在ET管的表面。一些研究人员在塑料管中添加了抗生素，但这并不能提供足够的抗菌活性，还会削弱ET管的塑料，然后ET管会坍塌并堵塞患者的呼吸道。相反，我们将以不可逆的方式将抗生素结合到表面。不可逆转地结合它们意味着抗生素不会从管子的塑料中扩散出来，而是停留在管子的表面，这就是感染问题的开始。我们将要附加的抗生素，QAC，已经在像漱口水这样的产品中使用了很长时间。它们的工作原理就像小分子“矛头”一样对抗细菌，一端有一个化学基团(矛头)，可以穿透细菌的膜(外层或“皮肤”)，还有一个长碳链(杆部)，可以进入细菌细胞。一旦发生这种情况，细菌的内容物就会从形成的洞中流出，细菌就会死亡。这种方法对于正确附着在ET管表面的QAC应该非常有效，因为它们仍将充当分子“矛”，并有效地提供一个“盔甲”表面，以对抗附着的细菌。我们还将在ET管的表面生长一层塑料层，以便在需要时“捕获”并释放抗生素，以提供对感染细菌的额外防御。我们以前曾通过将抗生素附着在塑料上进行过这种类型的研究工作，因此我们希望能够开发出一种新型的ET管，供医院制造和使用。这将减少ICU患者患肺炎的机会，帮助他们顺利康复，还将通过增加一种非常有效的新产品的销售，帮助该国的医疗器械行业。

For approximately 20 years we have been investigating the high death rate of patients in Intensive Care Units (ICUs) from the lung infection, pneumonia. Following surgery, patients are often admitted to ICUs where they can be carefully monitored. This extra care is required because the patient may be elderly, very weak or need specialised equipment to help in their recovery. A major challenge facing the medical staff in ICUs is to keep patients free from infection. Bacteria are a problem in hospitals, and many ICU patients die from pneumonia. Patients in ICUs are often taking medicines to weaken their immune systems to allow, for example, a transplant to be accepted by the body instead of being rejected. Unfortunately, this makes their bodies very susceptible to infection. A further complication is that the patient often has several tubes connecting their body to specialised equipment. One of these plastic tubes is an endotracheal (ET) tube, which is inserted into the patient's trachea to deliver air from an artificial ventilator into the lungs. Unfortunately, bacteria are attracted to the plastic of the ET tube. Communities of bacteria, known as biofilms, coat the plastic surface of the tube with a slime-like layer, similar to the bacterial plaque which forms on teeth. The biofilm is extremely difficult to kill with antibiotics due to its location on the inside wall of the ET tube and the slime-like substances which protect the bacterial cells. When ventilated air is pumped into the patient's ET tube some of the bacteria growing in the biofilm are shed from the surface and carried down into the lungs. This can result in serious cases of pneumonia. We have obtained ET tubes from patients who have either died or recovered in ICU and investigated how much and what types of bacteria are attached to the tubes. These studies have allowed us to develop our research plan to prevent bacteria infecting the ET tube by modification of its surface, which will ultimately reduce the number of patients dying in ICU. We will still use special kinds of antibiotic, known as quaternary ammonium compounds, or QACs, but instead of giving them by injection or as tablets we will permanently attach them to the ET tube surface. Some researchers have added antibiotics into the plastic tube, but this does not provide sufficient antimicrobial activity and it also weakens the plastic of the ET tube, which can then collapse and block the patient's airway. Instead, we will bind the antibiotics in an irreversible way to the surface. Binding them irreversibly means that antibiotics will not diffuse out of the plastic of the tube and will stay at its surface, which is where the problem with infection begins. The antibiotics we will attach, QACs, have been used in products like mouthwashes for a long time. They work like small molecular "spears" against bacteria, with a chemical group at one end (the spearhead), which can penetrate the membrane (the outside layer or "skin") of a bacterium, and a long carbon chain (the shaft), which can enter the bacterial cell. Once this happens the contents of the bacterium flow out of the hole formed and the bacterium dies. This approach should work very well for QACs attached properly to the ET tube surface as they will still act as molecular "spears" and effectively provide an "armoured" surface against adhering bacteria. We will also grow a plastic layer at the ET tube surface which will be able to "capture" and then release antibiotics when required to provide additional defence against the infecting bacteria.We have carried out this type of research work before by attaching antibiotics to plastics so we expect to be able to develop a new type of ET tube for manufacture and use in hospitals. This will reduce the chance of patients in ICU developing pneumonia, helping them to recover well, and will also help the medical device industry in this country though increased sales of a new and very effective product.