A Phase 1 Study to Assess Safety and Feasibility of Methylene Blue Photodynamic Therapy to Sterilize Deep Tissue Abscess Cavities

Deep tissue abscesses remain a significant cause of morbidity, mortality, and hospital stay despite improved surgical techniques and increasing use of perioperative antibiotics. Mortality ranges from 80-100% in undrained collections and, in patients with intraperitoneal abscesses, reported hospital stays have been 21-47 days. The development of image-guided percutaneous drainage accompanied by antimicrobial treatment has been shown to improve patient outcomes and can significantly reduce mortality in uncomplicated fluid collections to 5% and morbidity to 10-15%. Even under favorable conditions, the use of long-term antibiotics increases the risk of acquired resistance and incidence of polymicrobial infection, which may limit future options for antibiotic treatment. Further, in 23% of patients, percutaneous drainage and intravenous antibiotics fail, requiring open surgical drainage, particularly in patients with abscesses infected with yeast or abscesses due to a pancreatic process.

Photodynamic therapy (PDT), which exerts antimicrobial activity through the generation of reactive oxygen species, may serve as a useful adjunct to current standard care of treating deep tissue abscesses by reducing the microbial burden following drainage. Recent work from our group demonstrated the effectiveness of methylene blue photodynamic therapy (MB-PDT) against organisms within primary aspirate fluid obtained from 32 patients who underwent image-guided percutaneous drainage of an abscess cavity. We found that MB-PDT was effective against multiple classes of organisms, including yeast and those displaying drug resistance. In these complex samples, we found no evidence of resistance to MB-PDT. These preclinical results obtained with samples harvested from the kinds of abscesses that we propose to treat provide a compelling rationale for evaluating the technical feasibility and safety of advancing optical fibers through catheters into an abscess cavity and performing PDT at the time of drainage. This clinical strategy would offer a wide range of potential health benefits to patients with deep tissue abscess. Among these advantages are reduced surgical intervention, decreased spread of infection, shortened course of post-treatment antibiotic therapy, and decreased selective pressure for antibiotic resistance. Ultimately, this would promote early recovery, shorten hospital stay, and lead to lower overall health care costs for patients undergoing image-guided percutaneous abscess drainage.

Image guided percutaneous drainage is performed at the University of Rochester using CT, ultrasound, or fluoroscopy. Focused imaging is performed, which confirms that the collection is amenable to drainage. The site is prepared and draped in the usual sterile fashion. The overlying skin is anesthetized with 1% lidocaine. A Hawkins/micropuncture needle is inserted, and the location confirmed under image guidance. The needle is advanced and placement within the collection is confirmed with imaging. Syringe aspiration of the abscess material is collected and sent for gram stain and culture. The needle is exchanged for a dilator and the 018 wire is replaced with a Coon's wire. If abscess collection contains multiple loculations, the end of the Coon's wire will be used to break up the loculations. The tract is further dilated with a transitional dilator followed by placement of an appropriate sized All Purpose Draining Locking pigtail catheter (8-14 French) into the fluid collection. The abscess will be drained by aspiration with a syringe. The catheter will be secured to the skin using 2-0 silk or stat-lock, dressed appropriately and connected to a drainage bag.

After drainage, the cavity will be flushed with sterile saline as per routine procedure. A fiber-optic probe that has undergone high-level disinfection will be advanced through the same catheter/needle in order to make gentle contact with the wall of the cavity. Low-intensity white light will be delivered by a tungsten halogen lamp by a single fiber within the probe, and detected by eight other fibers within the probe. Following this, low-power laser light will be delivered by a fiber-coupled laser diode in order to excite methylene blue fluorescence. Emitted fluorescence will similarly be collected by the eight detection fibers contained within the probe. Upon completion of these measurements, the fiber-optic probe will be withdrawn, gently wiped with sterile gauze, and returned to the procedure cart. The total time required for both reflectance and fluorescence measurements generally ranges from 10-60 seconds.

Following this, and using the same catheter, the cavity will then be filled with sterile, clinical grade methylene blue solution diluted 10-fold from its stock concentration of 10 mg/mL. The volume introduced will be matched to the cavity volume, which we estimate will not exceed 270 mL. In the unlikely case of the entire methylene blue dose escaping into systemic circulation, this results in a full body dose of 3.85 mg/kg for a typical patient weight of 70 kg. This is below the range for which adverse events have been reported for methylene blue.