Novel antimicrobials are urgently needed to combat the global increase in antimicrobial resistance. Exeporfinium chloride (XF-73) is a synthetic dicationic porphyrin antimicrobial, acting through membrane disruption; with a secondary mechanism of action, activated via blue light exposure. The aim of this study was to assess the antimicrobial efficacy of XF-73 and photo-activated XF-73 against a panel of clinically relevant Gram-positive and Gram-negative microorganisms in planktonic and biofilm modes of growth. The antimicrobial efficacy of XF-73 was assessed through minimum inhibitory and bactericidal concentration (MIC/MBC) assays. The biofilm Calgary device generated twenty-four hour biofilms to assess the anti-biofilm effect of XF-73 on biofilm viability through viable cell counts and through minimum biofilm inhibitory and eradication concentrations (MBIC/MBEC) assays. The antimicrobial activity of photo-activated XF-73 was also assessed following fifteen minutes blue light exposure at 420 nm (light dose = 13.8 J/cm2). XF-73 expressed a greater bactericidal activity against Gram-positive planktonic bacteria in comparison to Gram-negative microorganisms as MBCs ranged from ≤ 0.125 – 4 μg/ mL and 128 – >256 μg/ mL respectively. Photo-activation of XF-73 enhanced the bactericidal properties against both Gram-positive and Gram-negative bacteria as MBCs decreased to ≤ 0.03 – 1 μg/ mL and 32 – 128 μg/ mL. Gram-positive biofilms were highly susceptible to XF-73 with MBEC’s ranging from 1 – 2 μg/ mL. Photo-activation increased the bactericidal effect of XF-73 against Gram-positive biofilms with MBEC’s ranging between ≤ 0.125 – 0.5 μg/ mL. XF-73 was unable to eradicate Gram-negative biofilms, but concentrations 128 – 512 μg/ mL significantly reduced biofilm viability (p= <0.0001). XF-73 is a potent antimicrobial against Gram-positive microorganisms in both planktonic and biofilm modes of growth. Photo-activation further enhances the bactericidal effect of XF-73 and potentially offers an adjunct form of treatment in comparison to current antimicrobial treatment strategies. Further research is warranted in this area
