Antimicrobial photodynamic therapy—a promising treatment for prosthetic joint infections

Abstract

Periprosthetic joint infection (PJI) is associated with high patient morbidity and a large financial cost. This study investigated Photodynamic Therapy (PDT) as a means of eradicating bacteria that cause PJI, using a laser with a 665-nm wavelength and methylene blue (MB) as the photosensitizer. The effectiveness of MB concentration on the growth inhibition of methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Pseudomonas aeruginosa and Acinetobacter baumannii was investigated. The effect of laser dose was also investigated and the optimized PDT method was used to investigate its bactericidal effect on species within planktonic culture and following the formation of a biofilm on polished titanium and hydroxyapatite coated titanium discs. Results showed that Staphylococci were eradicated at the lowest concentration of 0.1 mM methylene blue (MB). With P. aeruginosa and A. baumannii, increasing the MB concentration improved the bactericidal effect. When the laser dose was increased, results showed that the higher the power of the laser the more bacteria were eradicated with a laser power ≥ 35 J/cm2 and an irradiance of 35 mW/cm2, eradicating all S. epidermidis. The optimized PDT method had a significant bactericidal effect against planktonic MRSA and S. epidermidis compared to MB alone, laser alone, or control (no treatment). When biofilms were formed, PDT treatment had a significantly higher bactericidal effect than MB alone and laser alone for all species of bacteria investigated on the polished disc surfaces. P. aeruginosa grown in a biofilm was shown to be less sensitive to PDT when compared to Staphylococci, and a HA-coated surface reduced the effectiveness of PDT. This study demonstrated that PDT is effective for killing bacteria that cause PJI.

Composites of fatty acids and ceramic powders are versatile biomaterials for personalized implants and controlled release of pharmaceuticals

“…The influence of the fatty acid tail length on the degradation rate prompted us to investigate its effect on the release of methylene blue. Methylene blue is a common stain and drug that is used to treat methaemoglobinia and encephalopathy and it is under investigation as a treatment for Alzheimer's disease, fungal infections, malaria and implant infections [21][22][23][24]. Implants with TCP, methylene blue and fatty acids (C12-C18) were cast and placed in PBS at 37°C where after the methylene blue release was recorded at different time points ( Figure 5).…”

Dual-wavelength photo-killing of methicillin-resistant Staphylococcus aureus

“…In addition to antimicrobial killing with the use of light within the blue light spectrum (i.e., 400 nm-470 nm), there have been other light-based modalities that have effectively eliminated organisms. For example, MB-PDT, a commonly used light-based antimicrobial approach (which uses a photosensitizer [MB] that is activated by red light to generate ROS), has been used against an array of bacterial pathogens, inclusive of MRSA in vitro and in vivo (21,22). A study by Vecchio et al found that MB-PDT was able reduce the relative luminescence of a bioluminescent variant of MRSA USA300 inoculated onto a burn (30-minute incubation) by approximately 2 log 10 CFUs (22).…”

Antimicrobial Photodynamic Therapy to Control Clinically Relevant Biofilm Infections

“…Highly virulent microorganisms such as S. aureus and G − bacilli (such as E. coli ) can participate in early infection, while coagulase-negative staphylococci and Propionibacterium acnes are responsible for some delayed infections, and S. aureus , streptococci, and G − bacilli can contribute to late infections (Gbejuade et al, 2015 ). Recently, aPDT was reported as an efficient means of treating bacteria causing PJI (Briggs et al, 2018 ).…”