Coating of endotracheal tubes with sphingosine to prevent bacterial growth and ventilator-associated pneumonia

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Ventilator-associated pneumonia (VAP) is a serious clinical problem and an important cause of morbidity and mortality in critically ill patients. Bacterial infections of the upper airway combined with the development of bacterial biofilm on those tubes has proven to be an important factor. Our group was the first to show that sphingosine, a sphingolipid present in most eukaryotic membranes, is present in high concentrations in the respiratory epithelium and plays an important role in the innate immunity of the upper respiratory tract by preventing bacterial invasion into the lower airways. We have developed several novel methods of coating the surface of endotracheal tubes with sphingosine and phytosphingosine, a sphingosine analog that mimics the role of sphingosine in the mammalian trachea and bronchi. Two such methods are dip-coating the tubes with sphingosine or phytosphingosine or coating them with polydopamine, to which sphingosine and phytosphingosine are bound. The two methods achieved comparable results; the sphingosine or phytosphingosine coating prevents as much as 99% of adherence and growth of Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. However, although the stability of sphingosine and phytosphingosine on the plastic tube after dip coating was insufficient, the coating was very stable with the polydopamine technique, but this coating markedly reduced the flexibility of the tube. Thus, improved coating techniques with modified sphingosine derivatives that allow covalent and, thus, stable binding without changing the material properties of the plastic tube are required.We now aim (i) to synthesize sphingosine analogs that can covalently bind to polyvinyl chloride (PVC) tubes without changing their material properties, (ii) to test the bactericidal properties and the stability of these novel coatings in various biological fluids in vitro, (iii) to determine the stability of the coating and the potential toxicity or adverse effects of these coated catheters in the trachea in vivo, and (iv) to determine whether endotracheal tubes coated with sphingosine analogs prevent local and systemic bacterial infections in vivo in a mouse model.