Antimicrobial Efficacy of Continuous Low-Irradiance Phototherapy Against Multidrug-Resistant Organisms

The objective of this study is to report on the bactericidal effects of blue light administered at low irradiance for extended periods of time. Multidrug-resistant organisms (MDROs) utilize biofilms that can limit the efficacy of antibiotics, causing infection and impaired wound healing. Unlike high-energy systems, continuous low-irradiance phototherapy (CLIP) avoids thermal injury of healthy tissue and can be delivered for extended periods. Four MDRO species, two of which contained different antibiotic resistance genes, were exposed to 405 nm irradiation in vitro. The microbes were incrementally exposed to increasing dose-rates (irradiance; mW/cm²) over a 24-h time period. Cell viability and biomass reduction assays were conducted to quantify the antibacterial/antibiofilm effects. Primary human dermal fibroblasts were also exposed to CLIP to assess whether these dose-rates would impair cell viability or proliferation. CLIP exposure utilizing irradiances as low as 2.78 mW/cm² delivered over 24 h resulted in a >3.0-log (>99.9%) and >2.0-log (>99.0%) microbial load reduction when organisms were grown in planktonic and biofilm-encapsulated conditions, respectively. Crystal violet biofilm assays revealed destruction of extracellular biofilm architecture following CLIP exposure. Human fibroblast viability and proliferation were unaffected by CLIP. This is the first report demonstrating the antimicrobial efficacy of CLIP for MDROs found in infected wounds. CLIP did not compromise cultured human fibroblast growth and survival. This study demonstrated that very low fluence rates (irradiances) delivered over extended periods are potently antimicrobial. There is translational potential for CLIP to be fabricated as a wearable device that would enable continuous ambulatory care of wounds.