Matt Smithhart

Introduction. Ventilator associated pneumonia (VAP) is one of the most common hospital acquired infections and is characterized by the development of pneumonia 48 hours after mechanical ventilation.^1–3 A stepwise adherence of bacteria to an endotracheal tube (ETT), formation of biofilm on the ETT, and migration of biofilm into the lower respiratory tract has been shown to reduce the bacterial diversity of the lung microbiome which is thought to lead to the development of VAP.^1,4–6 Pseudomonas aeruginosa is one of the major causes of VAP and its pathogenicity and antibiotic resistance is associated with the formation of a biofilm.^1,3,5–7 In order to prevent the occurrence of P. aeruginosa mediated VAP, treatment of an ETT with sphingosine, a normal component of the bronchial and tracheal epithelium, serves as an attractive candidate regimen for VAP prevention.^4,8 Sphingosine displays bactericidal effects through binding to the bacterial cell membrane component, cardiolipin.⁸ Methods. Artificial liposomes containing cardiolipin were created and treated with sphingosine to determine effects of sphingosine on a plasma membrane.⁸ Moreover, bacterial cell membrane permeability and bactericidal effects of sphingosine were determined by quantifying bacterial cell ATP release after treatment of two strains of P. aeruginosa with sphingosine.⁸ Additionally, an endotracheal tube exposed to conditions similar to those that an ETT would be subject to in vivo was treated with sphingosine and immersed in a bacterial suspension to determine if sphingosine played a role in preventing bacterial adherence and growth.⁴ Mice were intubated with sphingosine-treated ETTs to determine the efficacy of sphingosine in the prevention of VAP.⁴ Results. Artificial liposomes containing cardiolipin showed a decrease in membrane fluidity.⁸ Treatment of bacteria with sphingosine reduced intracellular levels of ATP and increased extracellular levels of ATP, demonstrating that interaction of bacterial cell membranes with sphingosine results in an increase in bacterial cell membrane permeability, and ultimately, cell death.⁸ Treatment of an ETT with sphingosine reduced P. aeruginosa adherence to the ETT, and mice intubated with sphingosine-treated ETTs were protected from the development of severe pneumonia.⁴ Conclusions. VAP is one of the most common nosocomial infections and is primarily caused by P. aeruginosa.^1,7 Sphingosine displays bactericidal effects through binding to cardiolipin.  Sphingosine treatment of an ETT reduces bacterial adherence and growth, and protects intubated mice from the development of VAP.^4,8 Thus, treatment of ETTs with sphingosine may decrease the incidence of VAP.

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