title: Effect of sub-lethal challenge with Photodynamic Antimicrobial Chemotherapy (PACT) on the antibiotic susceptibility of clinical bacterial isolates.
abstract: This study aimed to determine the effect of sub-lethal challenge with Photodynamic Antimicrobial Chemotherapy (PACT) on the susceptibility of clinical Staphylococcus aureus and Pseudomonas aeruginosa isolates to both PACT and a range of antibiotics used in the treatment of infection caused by these bacteria. Clinical S. aureus and P. aeruginosa isolates were exposed to sub-lethal PACT with meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP) and methylene blue (MB) over a 72 h period. After exposure, susceptibility of surviving organisms to a range of antibiotics was determined and compared with the susceptibility of an untreated control. Surviving bacteria were also exposed to previously lethal photosensitizer-light combinations, to determine if susceptibility to PACT was affected by sub-lethal exposure. Exposure to sub-lethal PACT did not decrease susceptibility to antibiotics with the minimum inhibitory concentrations for 95% and 100% of P. aeruginosa and S. aureus isolates, respectively, within two doubling dilutions of the MIC of the untreated control. Similarly, habituation with sub-lethal PACT did not reduce susceptibility of P. aeruginosa isolates to PACT levels previously determined as lethal. A reduction in susceptibility to PACT following habituation was apparent for two S. aureus isolates with MB and for 1 S. aureus isolate with TMP. However, for two of these three isolates, the log reduction for habituated cells was still greater than 4 log(10). PACT remains an attractive potential treatment for infection caused by these bacteria.
authors.affiliation: School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors.forename: Corona M
authors.initials: CM
authors.lastname: Cassidy
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
authors.forename: Michael M
authors.initials: MM
authors.lastname: Tunney
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D006801:Humans; D008751:Methylene Blue / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000528:radiation effects; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000528:radiation effects
chemical_list: D000900:Anti-Bacterial Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; C021096:tetra(4-N-methylpyridyl)porphine; D008751:Methylene Blue