Antimicrobial blue light-activatable optical endotracheal tube to combat biofilms on the endotracheal tube

PROJECT SUMMARY/ABSTRACT Endotracheal intubation is a common hospital procedure implemented in patients requiring mechanical ventilation. However, biofilms formed on endotracheal tubes (ETTs) represent a leading cause of ventilator- associated pneumonia (VAP). VAP affects up to 28% of intubated patients and carries a 13% overall mortality.

Efforts to prevent VAP have included systemic antibiotics and silver-coated ETTs. However, systemic antibiotics are reported to have little effect on biofilm formation on ETTs. Although silver‐coated ETTs have been shown to reduce the VAP rate effectively, these tubes have a major limitation in being economically

feasible. Therefore, there is a critical need to develop new strategies that can effectively eradicate biofilms on ETTs and are also cost-effective. The objective of this R21 application is to explore the utility of a novel optical endotracheal tube (Optical-ETT), which can be activated by antimicrobial blue light (aBL; 405 nm)

and subsequently emit aBL uniformly from the ETT surface, to combat biofilms on ETTs. Our team is a pioneer in the field of aBL. Our central hypothesis is that Optical-ETT can effectively prevent biofilm formation and eradicate preexisting biofilm on the ETT. To address this hypothesis, we propose two Specific Aims.

In Aim 1, we will conduct in vitro studies to determine the anti-biofilm efficacy of Optical-ETT. Biofilms will be formed on ETT segments in the growth medium. To prevent biofilm formation on ETTs, Optical-ETTs will be "activated" by aBL within 3 h after bacterial inoculation. To eradicate preexisting biofilms on ETTs, Optical-

ETTs will be "activated" by aBL 24, 48, and 96 h after bacterial inoculation when biofilms of different stages have formed. The efficacy found with Optical-ETTs will be compared with that of silver-coated ETTs. In Aim 2, we will determine the anti-biofilm efficacy and safety of Optical-ETT in vivo using a swine model of

endotracheal intubation. Animals will be challenged by instilling bacterial suspensions (5 mL at 108 CFU/mL) into the buccal pouch 30 min after intubation. To prevent biofilm formation on ETTs, Optical-ETTs will be activated by aBL within 3 h after bacterial challenge. To eradicate preexisting biofilms on ETTs, the activation

of Optical-ETTs by aBL will be delayed until 24 h after bacterial challenge when mature biofilms have formed. The bacterial loads of ETTs, the tracheas, and the lungs will be quantified. To evaluate the safety of Optical- ETT, the tracheal tissue damages will be assessed using histology. The potential inflammatory response

triggered by Optical-ETT will be analyzed by measuring the proinflammatory cytokine profile in the bronchoalveolar lavage fluid. Additionally, the effect of Optical-ETT on the ciliary motion will be evaluated using micro-optical coherence tomography, a unique imaging technology invented in our department.

The most important impact of this application resides in the opening of a branch of study on the novel aBL- activatable Optical-ETT to combat biofilms on ETTs. Successful completion of the Specific Aims in this application will provide initial preclinical evidence to determine the effectiveness and safety of the Optical-ETT.