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

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.

IMPACT SUMMARY

Who will benefit from this research, and how will they benefit from this research?

Four groups could be clear beneficiaries of this research programme if successful:

1. Who: The first group is that of mechanically ventilated patients in Intensive Care Units (ICU). The increasing incidence of hospital-acquired infection is a disturbing trend, resulting in significant patient mortality, especially in the case of ventilator-associated pneumonia (VAP). This arises in ICU patients receiving ventilation via an endotracheal (ET) tube. The incidence of VAP can be as high as 52% and the mortality of patients with VAP as high as 71% despite antibiotic therapy. Several of our previous studies in this area have shown that growth of microbial pathogens in the form of antibiotic-resistant biofilms on ET tube surfaces plays a key role in VAP. The ET tube bypasses host defences and provides inhaled microorganisms with facile access to the airways.

How: To-date, antibiotic therapy has not been successful in preventing biofilm formation or in eradicating established biofilms on ET tubes. Our novel approach will provide site-specific antimicrobial activity in a controlled and sustained manner on the ET tube surface for the prevention of VAP, and improved patient outcomes on a global scale.

2. Who: Healthcare organisations/governments. Medical device-related infection is estimated to cost the NHS in the order of £1 billion per annum due to the extra clinical care involved with patients who become infected in hospital.

How: Our technology, aimed at reducing the incidence of VAP, will reduce hospital stays. As a result, budgetary costs associated with the extended hospital stays and treatment of seriously ill patients with pneumonia will be reduced.

3. Who: The third group is the UK medical device and polymer industry.

How: They will benefit through potential commercialisation of the improved ET tube and the market share expected from such global uptake. Longer-term development of an extended range of next-generation infection-resistant technologies will help ensure future success of the UK's economy and attract international investment.

4. Who: The broader academic community, including polymer and chemical engineers and microbiological research scientists.

How: They will benefit from the novel insights generated and disseminated through this programme. In particular, the research outcomes are expected to make important contributions to the current knowledge base surrounding the process of bacterial attachment to surfaces, and provide potentially efficacious strategies to combat highly resilient biofilm-associated infections.