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室（ICU）中肺部感染、肺炎患者的高死亡率。手术后，患者通常被送入ICU，在那里他们可以得到仔细的监测。这种额外的护理是必要的，因为病人可能是老年人，非常虚弱或需要专门的设备来帮助他们恢复。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，允许身体接受移植而不是被排斥。不幸的是，这使得他们的身体很容易受到感染。另一个复杂的问题是，病人往往有几个管道连接他们的身体到专门的设备。这些塑料管之一是气管内（ET）管，其插入患者的气管以将空气从人工呼吸机输送到肺部。不幸的是，细菌被吸引到ET管的塑料上。被称为生物膜的细菌群落用类似于牙齿上形成的细菌菌斑的粘液层覆盖在管子的塑料表面。由于生物膜位于ET管的内壁上并且具有保护细菌细胞的粘液状物质，因此使用抗生素很难杀死生物膜。当通风空气被泵入患者的ET管时，生物膜中生长的一些细菌从表面脱落并被带入肺部。这可能导致严重的肺炎病例。我们从ICU中死亡或康复的患者身上获得了ET管，并调查了有多少和什么类型的细菌附着在管上。这些研究使我们能够制定我们的研究计划，通过修改其表面来防止细菌感染ET管，这将最终减少ICU中死亡的患者数量。我们仍将使用特殊种类的抗生素，称为季铵化合物，或QAC，但不是通过注射或片剂给药，我们将永久地将它们附着在ET管表面。一些研究人员已经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，而且还会削弱ET管的塑料，从而导致ET管塌陷并阻塞患者的气道。相反，我们将以不可逆的方式将抗生素结合到表面。不可逆地结合它们意味着抗生素不会从塑料管中扩散出来，并将停留在其表面，这是感染问题开始的地方。我们将附上的抗生素，QAC，已经在漱口水等产品中使用了很长时间。它们就像小分子的“矛”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”），还有一条长碳链（轴），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孔中流出，细菌就会死亡。这种方法对于适当地附着到ET管表面的QAC应该非常有效，因为它们仍然充当分子“矛”，并且有效地提供针对粘附细菌的“装甲”表面。我们亦会在气管插管的表面种植一层塑胶层，让它可以“捕捉”抗生素，然后在有需要时释放抗生素，以加强对感染细菌的防御。我们曾进行这类研究工作，把抗生素附着在塑胶上，所以我们期望能够研制出一种新型的气管插管，供医院制造和使用。这将减少重症监护室患者患肺炎的机会，帮助他们恢复良好，也将有助于该国的医疗器械行业，虽然增加了一种新的和非常有效的产品的销售。

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.