Antimicrobial PDT for prosthetic joint infections

Customer case

Royal National Orthopaedic Hospital at UCL, Stanmore in London, UK is an internationally leading Centre of Excellence and tertiary referral centre for complex orthopedic conditions. Close collaboration between clinicians and engineers facilitates high-quality research into orthopedic implant fixation and bone regeneration. Focus is on translational themes that include biomaterials, stem cells, the design and follow-up of implants, bone graft substitute materials and implant infections. PDT has been studied as an alternative to antibiotics to more effectively tackle infections following hip & knee replacement surgeries.

Modulight products: ML7000 series laser with two wavelengths: 665 and 689 nm

Laser use: Methylene blue-meditated PDT for prosthetic joint infections

Professor Melanie Coathup

 

 

Professor Timothy Briggs

 

Link to the study:

Motivation for the study

Periprosthetic joint infections after hip and knee replacement surgeries are associated with high patient morbidity and a large financial cost. Challenging two-stage revision surgeries are required with long antibiotics regimes that can have limited efficacy and cannot eradicate drug-resistant strains like MRSA (methicillin-resistant Staphylococcus aureus). This study aims to investigate the potential of photodynamic therapy with methylene blue to eradicate problematic bacteria associated with joint infections.

 

Experiments

To determine the effectiveness of methylene blue PDT it is important to understand the effect of both drug and light dose on treatment response. The effectiveness of different methylene blue concentrations on MRSA bacterial growth inhibition was first studied on Petri dishes with or without laser light (ML7000 series laser system, 665 nm, 35 mW/cm2, 16 min irradiation). Different laser doses (15, 25, 30, 35, 40 and 45 J/cm2) were also studied with constant methylene blue concentration (0.3 mM) to understand how increasing light dose affects the treatment response. Plates were incubated at 37 ⁰C and visually inspected the next day.

 

 

Results

Optimal methylene blue concentration against MRSA

Methylene blue alone had little effect against MRSA: while increasing the concentration of methylene blue has some effect, a significant number of colonies are left even at the highest concentration studied. When combined with laser activation, MRSA colonies are effectively eradicated at all studied concentrations of methylene blue.

 

 

Optimal laser dose for antimicrobial PDT

Increasing the laser power improved the efficacy of antimicrobial PDT. Control plates where no laser was applied had no effect on bacterial growth, while laser doses of 15 J/cm2 and 30 J/cm2 were effective but a few resistant colonies were left. Laser light dose of 35 J/cm2 was the lowest laser dose that eradicated all bacteria.

 

 

 

Photos from the original publication. Reproduced under Creative Commons Attribution 4.0 International License.

 

Conclusions:
Methylene blue was demonstrated to be an effective antimicrobial agent when combined with 665 nm laser light, while without laser light it had very limited efficacy. Increasing the laser dose increased the bactericidal effect, with a dose of 35 J/cm2 being the lowest laser dose to eradicate all bacteria. This optimized treatment protocol should be next studied in vivo before being used in a human clinical trial. Antimicrobial PDT may become a beneficial and safe treatment for prosthetic joint infections in future thanks to its speed of action and lack of bacterial resistance.

 

 

Related Publications

Antimicrobial photodynamic therapy–a promising treatment for prosthetic joint infections
Timothy Briggs, Gordon Blunn, Simon Hislop, Rita Ramalhete, Caroline Bagley, David McKenna, Melanie Coathup
Lasers Med Sci, 2018, 33 (3)

 

 

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