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 ¿ 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.