Reduction of Endotracheal Tube Biofilms using Antimicrobial Photodynamic Therapy

Background: The leading cause of patient death from hospital-acquired infections is pneumonia. Ventilator-associated pneumonia (VAP) is reported to occur in 12 to 25% of patients who require mechanical ventilation. Patients who develop VAP have a significantly longer need for mechanical ventilation (14 days vs. 5 days), a significantly longer stay in the ICU (11 days vs. 6 days),a significantly longer stay in the hospital (25 days vs. 14 days)  and a mortality rate of 24 to 71%. The cost of treating VAP is conservatively estimated to be $1.8 billion dollars annually. The endotracheal (ET) tube has long been recognized as a major factor in the development of VAP since the microorganisms and biofilm harbored within the ET tube become dislodged during mechanical ventilation and have direct access to the lungs. These life-threatening infections are perpetuated by continuous microbiological seeding from the ET tube biofilms and become difficult to treat due to the propensity of the biofilm microorganisms to develop antibiotic resistance.   Antimicrobial photodynamic therapy (aPDT) is a non-antibiotic broad spectrum antimicrobial treatment that has been demonstrated to eradicate antibiotic resistant bacteria and biofilms.

Objective: The objective of this study was to demonstrate the effectiveness of a non-invasive aPDT treatment method of eradicating antibiotic resistant biofilms/microorganisms from ET tubes without removing the tube from the patient or interrupting the ventilator circuit or cycle in an in vitro and ex vivo model.

Methods: Antibiotic resistant polymicrobial biofilms of Pseudomonas aerugenosa and MRSA were grown in ET tubes and treated, under standard ventilator conditions, with a methylene blue photosensitizer and 664nm non-thermal activating light.  Cultures of the lumen of the ET tube were obtained before and after light treatment to determine efficacy of biofilm reduction.  An ex vivo study of aPDT treated ET tubes from acutely extubated patients was also performed to demonstrate the effectiveness of the treatment on human native grown endotracheal tube biofilms.

Results: The in vitro ET tube biofilm study demonstrated that aPDT reduced the ET tube polymicrobial biofilm by >99.9% after a single treatment.  The ex vivo study demonstrated that 65% of the ET tubes treated obtained complete eradication of the pathogenic organisms after one PDT treatment (p<0.05) and another 15% obtained a significant reduction in the pathogenic organisms.

Conclusions: aPDT can effectively treat polymicrobial antibiotic resistant biofilms in an ET tube both in vivo and in extubated human endotracheal tube studies.  Human clinical studies are currently underway to assess the safety and efficacy of this treatment on the prevention of VAP.