title: Pre-clinical in vitro and in vivo studies to examine the potential use of photodynamic therapy in the treatment of osteomyelitis.
abstract: Osteomyelitis can lead to severe morbidity and even death resulting from an acute or chronic inflammation of the bone and contiguous structures due to fungal or bacterial infection. Incidence approximates 1 in 1000 neonates and 1 in 5000 children in the United States annually and increases up to 0.36% and 16% in adults with diabetes or sickle cell anaemia, respectively. Current regimens of treatment include antibiotics and/or surgery. However, the increasing number of antibiotic resistant pathogens suggests that alternate strategies are required. We are investigating photodynamic therapy (PDT) as one such alternate treatment for osteomyelitis using a bioluminescent strain of biofilm-producing staphylococcus aureus (S. aureus) grown onto kirschner wires (K-wire). S. aureus-coated K-wires were exposed to methylene blue (MB) or 5-aminolevulinic acid (ALA)-mediated PDT either in vitro or following implant into the tibial medullary cavity of Sprague-Dawley rats. The progression of S. aureus biofilm was monitored non-invasively using bioluminescence and expressed as a percentage of the signal for each sample immediately prior to treatment. S. aureus infections were subject to PDT 10 days post inoculation. Treatment comprised administration of ALA (300 mg kg(-1)) intraperitoneally followed 4 h later by light (635 +/- 10 nm; 75 J cm(-2)) delivered transcutaneously via an optical fiber placed onto the tibia and resulted in significant delay in bacterial growth. In vitro, MB and ALA displayed similar cell kill with > or =4 log(10) cell kill. In vivo, ALA-mediated PDT inhibited biofilm implants in bone. These results confirm that MB or ALA-mediated PDT have potential to treat S. aureus cultures grown in vitro or in vivo using an animal model of osteomyelitis.
authors.affiliation: Ontario Cancer Institute, University Health Network, University of Toronto, 610 University Ave., Toronto, Canada. sbisland@uhnres.utoronto.ca
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Bisland
authors.forename: Claudia
authors.initials: C
authors.lastname: Chien
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.forename: Shane
authors.initials: S
authors.lastname: Burch
mesh_terms: D000622:Aminolevulinic Acid / Q000528:radiation effects / Q000627:therapeutic use*; D000818:Animals; D018441:Biofilms / Q000254:growth & development; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D020007:Implants, Experimental / Q000382:microbiology; D066298:In Vitro Techniques; D008027:Light; D008163:Luminescent Measurements; D008751:Methylene Blue / Q000737:chemistry; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000528:radiation effects / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; D008751:Methylene Blue