Photodynamic therapy for perforated appendicitis

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The primary goal of this proposal is to evaluate the antimicrobial efficacy of photodynamic therapy in the context of perforated appendicitis. This will be accomplished using in vivo rabbit models and in vitro evaluation of human specimens. Appendicitis is the most common general surgical condition affecting children and contributes to more morbidity and health care resource utilization than any other pediatric general surgical condition. Approximately ⅓ of pediatric cases in the United States present with perforated appendicitis (PA), with these perforated cases associated with higher costs, longer hospitalizations, higher hospital readmission rates, and worse postoperative outcomes. Prolonged antibiotic therapy after appendectomy remains the mainstay for treatment for intra-abdominal infection. This results in long hospital stays and may not be effective against antibiotic resistant strains, highlighting the need for alternative therapies. Photodynamic therapy (PDT), which exerts antimicrobial activity through photochemical generation of reactive oxygen species, is broad spectrum and fast acting, efficacious against antibiotic-resistant strains, and does not result in acquired resistance. Given that the intra-abdominal infection associated with PA is polymicrobial and often complicated by bacterial resistance to common antibiotics, PDT is an appealing adjunct to the treatment of intra-abdominal infection in perforated appendicitis and could further be used to treat abscess formation post-appendectomy. The objective of this study is to demonstrate proof-of-concept of antimicrobial PDT as a treatment of intra-abdominal infection in perforated appendicitis in a rabbit model, as well as efficacy against bacteria isolated from human samples. This high risk, high reward study could revolutionize management of PA, and drastically reduce hospital stay and complications. Aim 1 – Demonstrate feasibility and efficacy of photodynamic therapy in a rabbit model of perforated appendicitis. Using an established rabbit model of PA, a prospective study will be performed to assess reduction of bacterial burden in the peritoneal cavity following methylene blue photodynamic therapy (MB- PDT). Bacterial load will be quantified pre- and post-PDT, and compared to control animals that receive illumination without MB. It is hypothesized that MB-PDT will result in a reduction of ≥99.9% in total bacterial population, with potential variation in killing of specific bacterial species found in the intestinal flora. Aim 2 – Demonstrate efficacy of photodynamic therapy in vitro for bacteria isolated from patients with perforated appendicitis. Bacteria isolated from aspirated peritoneal fluid captured from pediatric patients undergoing appendectomy for PA will be characterized. MB-PDT will then be performed on both planktonic cultures and biofilms. It is hypothesized that PDT will significantly reduce bacterial burden, with biofilms potentially requiring larger drug/light doses for comparable efficacy.