Photodynamic antimicrobial chemotherapy for <em>Staphylococcus aureus</em> and multidrug-resistant bacterial burn infection in vitro and in vivo

Abstract

Background and objectives Antibiotic resistance has emerged as one of the most important determinants of outcome in patients with serious infections, along with the virulence of the underlying pathogen. Photodynamic antimicrobial chemotherapy (PACT) has been proposed as an alternative approach for the inactivation of bacteria. This study aims to evaluate the antibacterial effect of sinoporphyrin sodium (DVDMS)-mediated PACT on Staphylococcus aureus and multidrug resistant S. aureus in vitro and in vivo. Materials and methods Bacteria were incubated with DVDMS and exposed to treatment with light. After PACT treatment, colony-forming units were counted to estimate the bactericidal effect. Intracellular reactive oxygen-species production was detected by flow cytometry. Flow cytometry and fluorescence-microscopy detection of bacterial cell-membrane permeability. Enzyme-linked immunosorbent assays were used to determine expression of VEGF, TGFβ 1 , TNFα, IL6, and bFGF factors in burn infection. Results DVDMS-PACT effectively killed bacterial proliferation. Intracellular ROS levels were enhanced obviously in the PACT-treatment group. SYTO 9 and propidium iodide staining showed a decrease in the ratio of green:red fluorescence intensity in the PACT-treatment group in comparison to the control group. Enzyme-linked immunosorbent-assay results revealed that in the healing process, the expression of bFGF, TGFβ 1 , and VEGF in the treatment group were higher than in the control group, which inhibited inflammation-factor secretion. In addition, skin-tissue bacteria were reduced after treatment. Conclusion These results indicate that DVDMS-PACT presents significant bactericidal activity and promotes wound healing after burn infections.

Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies

“…The animal species used in the 19 studies were mice (n = 16) and rats (n = 3) . Of the 16 mouse studies, nine used BALB/c mice, 4 utilised Swiss albino mice, two used C57BL/ksj db/db mice, and one used CD1 mice . One study did not report the mouse strain that was used.…”

“…To investigate the antimicrobial effect of PDT, the wounds in all studies were inoculated with one or two species of bacteria. The majority were P. aeruginosa and methicillin‐resistant S. aureus . Others were unresistant S. aureus strains, Escherichia coli , and Acinetobacter baumannii …”

“…It was used in two studies . Other used photosensitisers were 5‐phenyl‐10; 15, 20‐tris (N‐methyl‐4‐pyridyl) porphyrin chloride (PTMPP); sinoporphyrin sodium (also known as DVDMS); indocyanine green (ICG); pentalysine β‐carbonylphthalocyanine zinc (ZnPc‐[Lys] 5 ); zinc phthalocyanine tetrasulfonate (ZnPc‐S 4 ); poly‐L‐lysine conjugate of chlorine p6 (pl‐cp6), β‐lactamase‐activated EtNBS (LAEtNBS); RLP068/Cl, toluidine blue O (TBO); polyethylenimine‐chlorin(e6) (PEI‐ce6); and poly‐ l ‐lysine‐chlorin e6 (pL‐ce6) …”

“…The photosensitisers were administered topically in 13 studies, by subcutaneous injection in one study, and by intraperitoneal injection in another study . In one study, burn wounds were simultaneously treated by both topical application and injection under the wound .…”

“…Two studies used 410‐nm light‐emitting diodes (LEDs), one study used an 808‐nm diode laser, and one study did not mention the wavelength of the light source . When visible light was used, the fluence ranged from 6 to 450 J/cm 2 , and the energy density ranged from 84 to 300 mW/cm 2 . For the 808‐nm diode laser, the fluence was 450 J/cm 2 …”