Selective antimicrobial photodynamic therapy of clinical isolates from patients with infected diabetic foot ulcers using a small cationic chlorin.

Diabetic foot ulcers (DFUs) are a major complication of diabetes mellitus and the principal factor contributing to lower limb amputations. Antimicrobial photodynamic therapy (aPDT) is a promising therapeutic strategy because it is not limited by drug resistance. A new photosensitizer, a low molecular weight dicationic imidazolyl chlorin (IC-H-Me2+), was developed for aPDT to improve permeation in biofilms and light absorption in the phototherapeutic window. The efficacy of aPDT with IC-H-Me2+ was tested against biofilms produced by methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S. aureus (MSSA), Staphylococcus epidermidis, and Pseudomonas aeruginosa isolates from patients with DFUs, both alone and combined with potassium iodide (KI). aPDT with 1 µM IC-H-Me2+ and a 1-h incubation period, followed by exposure to a light dose of 5 J/cm2 using a 660 nm LED, reduced the viability of all biofilms by >3 log of colony-forming units (CFU) in one single aPDT session. Furthermore, when this photosensitizer and light doses were combined with 50 mM KI, most biofilms were completely eradicated. This combination generates triiodide ions in the biofilms, which increase the response to aPDT. Up to 15 log CFU/mL reduction of biofilms was obtained with one single treatment. This same combination does not significantly reduce the viability of human epidermal keratinocytes. The eradication of MRSA biofilms from clinical isolates is selective. These results demonstrate that IC-H-Me2+, properly formulated with KI, has the potential to selectively eradicate biofilms established in infected wounds and decrease amputation rates in patients with DFU.