Methylene blue-enhanced photodynamic and sonodynamic therapy againstStaphylococcus aureus: From laboratory research...

Antibiotic resistance among multidrug-resistant pathogens necessitates alternative antimicrobial strategies. Photodynamic therapy (PDT) and sonodynamic therapy (SDT), particularly with methylene blue (MB), show promise but remain underexplored in clinical contexts.

We conducted an in vitro evaluation of MB-PDT and SDT against Staphylococcus aureus, a major cause of skin and soft tissue infections. Assays included growth curve analysis, scanning electron microscopy (SEM) to assess bacterial ultrastructure. A pilot clinical study in 20 healthy volunteers assessed in vivo antimicrobial efficacy and tolerability under standardized conditions.

In vitro, MB demonstrated antimicrobial activity under PDT, with further potentiation by SDT and repeated irradiation. SEM confirmed structural disruption and lysis of S. aureus following combination therapy. In vivo, both MB-PDT and PDT+SDT achieved significant bacterial log reductions compared with baseline (p < 0.0001), with the highest efficacy observed under repeated irradiation plus SDT. The most significant effect was observed with repeated irradiation (2 × 30 J.cm⁻²) in combination with ultrasound (1 MHz, 1 W/cm²), with an average reduction of 2.424 log₁₀ (SD = 0.652).

MB-mediated PDT and PDT+SDT are safe, well tolerated, and effective against S. aureus on skin. These approaches provide localized antimicrobial activity independent of antibiotic resistance and warrant further optimization for clinical application.