Photodynamic Therapy Combined with Antibiotics or Antifungals against Microorganisms That Cause Skin and Soft Tissue Infections: A Planktonic and Biofilm Approach to Overcome Resistances

Abstract

The present review covers combination approaches of antimicrobial photodynamic therapy (aPDT) plus antibiotics or antifungals to attack bacteria and fungi in vitro (both planktonic and biofilm forms) focused on those microorganisms that cause infections in skin and soft tissues. The combination can prevent failure in the fight against these microorganisms: antimicrobial drugs can increase the susceptibility of microorganisms to aPDT and prevent the possibility of regrowth of those that were not inactivated during the irradiation; meanwhile, aPDT is effective regardless of the resistance pattern of the strain and their use does not contribute to the selection of antimicrobial resistance. Additive or synergistic antimicrobial effects in vitro are evaluated and the best combinations are presented. The use of combined treatment of aPDT with antimicrobials could help overcome the difficulty of fighting high level of resistance microorganisms and, as it is a multi-target approach, it could make the selection of resistant microorganisms more difficult.

Keywords: MDR; SSTI; antimicrobial agents; photoinactivation; resistance.

Figure 1

Mechanism of action of antimicrobial photodynamic therapy: photosensitizer molecules (PS) in ground state (¹PS) are activated by light (hv) of a wavelength that matches the absorption wavelength of the molecule. PS reaches an excited state, first singlet (¹PS*), very unstable, and rapidly triplet (³PS*). This reacts with the oxygen by transferring electrons (Type I) or energy (Type II) in its reversion to the ground state (¹PS*). Type I reaction is characterized by the formation of reactive oxygen species (ROS) and Type II by the formation of singlet oxygen (¹O₂⁻). These molecules are highly reactive and are capable of damaging cells resulting in a toxic effect for microorganisms (Adapted with permission from ref. [18], 2018, Pérez-Laguna et al.).