(591e) Antimicrobial Peptide Amphiphile (AMPA) Medical Product Coatings for the Prevention of Nosocomial Infections

Nosocomial (hospital-acquired) infections are a significant issue in the clinical medicine today. One common origin of infection is through bacterial growth on equipment and materials in contact with patients. The most common nosocomial infection is ventilator-associated pneumonia (VAP), for which an endotracheal tube (ETT) provides a surface that facilitates bacteria colonization of deep lung tissue. Approximately 21% of patients in Intensive Care Units (ICUs) acquire VAP and around 10% of those will die from the infection. While treatment with antibiotics can sometimes help, many bacteria are becoming drug resistant and limit drug exposure by creating a protective biofilm.

Antimicrobial peptides show considerable promise as a novel, effective alternative to traditional antibiotics in combating VAP. Recent advances in peptide and peptide amphiphile therapeutics have resulted in products that have been successfully translated to the clinic. With inspiration from a collaborator and the literature, we have designed, synthesized, and evaluated a suite of novel antimicrobial peptide amphiphiles (AMPAs), including a cyclic AMPA, a linear biologically-homologous AMPA, and a polypeptide AMPA produced via N-carboxyanhydride ring-opening polymerization. We have designed an inexpensive and simple additive manufacturing method for coating medical-grade plastics with AMPAs to prevent bacterial growth, overcoming key challenges associated with the prolonged, localized delivery and stability of peptide amphiphiles. Using atomic force microscopy, we have shown successful coating of a thin AMPA films on ETTs. Submersion coating experiments have established our ability to apply this method of coating to several different AMPAs as well as with multiple kinds of medical-grade plastics. We have established that our suite of AMPA coatings are capable of reducing bacterial adhesion and biofilm growth through preliminary in vitro analysis against clinically-relevant bacteria but show minimal toxicity to mammalian cells. These preliminary in vitro results indicate that AMPAs outperform their peptide counterparts and, due to the stable nature of the AMPA film, prevent bacterial adhesion for significantly longer than peptide alone. These results provide strong evidence that AMPA-coated ETTs will be an effective method of preventing VAP clinically.