Inactivation kinetics and lethal dose analysis of antimicrobial blue light and photodynamic therapy

Photodiagnosis Photodyn Ther. 2019 Dec:28:186-191. doi: 10.1016/j.pdpdt.2019.08.022. Epub 2019 Aug 17.

Abstract

Background: Antimicrobial Photodynamic therapy (A-PDT) has been used to treat infections. Currently, microbial inactivation data is reported presenting survival fraction averages and standard errors as discrete points instead of a continuous curve of inactivation kinetics. Standardization of this approach would allow clinical protocols to be introduced globally, instead of the piecemeal situation which currently applies.

Methods: To this end, we used a power-law function to fit inactivation kinetics and directly report values of lethal doses (LD) and a tolerance factor (T) that informs if inactivation rate varies along the irradiation procedure. A deduced formula was also tested to predict LD for any given survival fraction value. We analyzed the photoantimicrobial effect caused by red light activation of methylene blue (MB-APDT) and by blue light (BL) activation of endogenous microbial pigments against 5 clinically relevant pathogens.

Results: Following MB- APDT, Escherichia coli and Staphylococcus aureus cells become increasingly more tolerant to inactivation along the irradiation process (T < 1). Klebsiella pneumoniae presents opposite behavior, i.e., more inactivation is observed towards the end of the process (T > 1). P. aeruginosa and Candida albicans present constant inactivation rate (T˜1). In contrast, all bacterial species presented similar behavior during inactivation caused by BL, i.e., continuously becoming more sensitive to blue light exposure (T > 1).

Conclusion: The power-law function successfully fit all experimental data. Our proposed method precisely predicted LD and T values. We expect that these analytical models may contribute to more standardized methods for comparisons of photodynamic inactivation efficiencies.

Keywords: Antimicrobial Photodynamic Therapy; Bacteria; Fungi; Microbial control; Photoantimicrobial; Photodynamic antimicrobial chemotherapy; Photoinactivation.

MeSH terms

  • Anti-Infective Agents / pharmacokinetics
  • Anti-Infective Agents / pharmacology*
  • Bacteria / drug effects*
  • Candida albicans / drug effects*
  • Dose-Response Relationship, Drug
  • Escherichia coli / drug effects
  • Klebsiella pneumoniae / drug effects
  • Methylene Blue / pharmacokinetics
  • Methylene Blue / pharmacology*
  • Microbial Viability / drug effects*
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacokinetics
  • Photosensitizing Agents / pharmacology*
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcus aureus / drug effects

Substances

  • Anti-Infective Agents
  • Photosensitizing Agents
  • Methylene Blue