Antimicrobial Photodynamic Therapy With New Methylene Blue and Its Combined Effect With Antibiotics Against MDR Acinetobacter baumannii

ABSTRACT

The present study aimed to evaluate the antibacterial efficacy of new methylene blue‐mediated antimicrobial photodynamic therapy (NMB‐mediated aPDT) in combination with tigecycline and colistin against multidrug‐resistant (MDR) A. baumannii and to explore ROS production as a possible mechanism contributing to the enhanced antibacterial activity of the combined treatments. MIC determination, sublethal irradiation and aPDT assays, checkerboard analysis, and ROS detection were performed. MIC of NMB for this MDR strain was greater than 100 μg/mL. Under various radiation times, aPDT at 12.5 μg/mL NMB was considered a sublethal dose that represented with a reduction of 1.7–2.6 log ₁₀ compared with control, and aPDT at 25 and 50 μg/mL were considered lethal doses that resulting in more reduction of bacterial counts to 3.23–4.3 log ₁₀ CFU/mL and 2.92–4.0 log ₁₀ CFU/mL, respectively. The irradiated NMB at 25 μg/mL and tigecycline at 1/4 × MIC showed a synergistic interaction. In addition, multiple additive interactions were observed at other concentrations of NMB and tigecycline, as well as with colistin at sub‐MIC concentrations, and these findings were further confirmed by CFU counting. The increased production of ROS was effectively detected following aPDT alone and in combination of antibiotic with aPDT. These findings suggest that NMB‐mediated aPDT alone and in combination with colistin or tigecyclines can be a promising approach to eradicate infections associated with MDR A. baumannii and reduces the development of further antibiotic resistance.