Antimicrobial Photodynamic Therapy Involving a Novel Photosensitizer Combined With an Antibiotic in the Treatment of Rabbit Tibial Osteomyelitis Caused by Drug-Resistant Bacteria.

Osteomyelitis is deep tissue inflammation caused by bacterial infection. If such an infection persists, it can lead to dissolution and necrosis of the bone tissue. As a result of the extensive use of antibiotics, drug-resistant bacteria are an increasingly common cause of osteomyelitis, limiting the treatment options available to surgeons. Photodynamic antibacterial chemotherapy has attracted increasing attention as a potential alternative treatment. Its advantages are a broad antibacterial spectrum, lack of drug resistance, and lack of toxic side effects. In this study, we explored the impact of the new photosensitizer LD4 in photodynamic antimicrobial chemotherapy (PACT), both alone and in combination with an antibiotic, on osteomyelitis. A rabbit tibial osteomyelitis model was employed and microbiological, histological, and radiological studies were performed. New Zealand white rabbits (n = 36) were randomly divided into a control group, antibiotic group, PACT group and PACT + antibiotic group for treatment. In microbiological analysis, a reduction in bacterial numbers of more than 99.9% was recorded in the PACT group and the PACT + antibiotic group 5 weeks after treatment (p < 0.01). In histological analysis, repair of the damaged bone tissue was observed in the PACT group, and bone repair in the PACT + antibiotic group was even more significant. In radiological analysis, the X-ray Norden score showed that the severity of bone tissue defects or destruction followed the pattern: PACT + antibiotic group < PACT group < antibiotic group < control group.

In Vitro and In Vivo Demonstration of Ultraefficient and Broad-Spectrum Antibacterial Agents for Photodynamic Antibacterial Chemotherapy.

Increasing threats from both pathogenic infections and antibiotic resistance highlight the pressing demand for nonantibiotic agents and alternative therapies. Herein, we report several new phenothiazinium-based derivatives, which could be readily synthesized via fragment-based assembly, which exhibited remarkable bactericidal activities both in vitro and in vivo. Importantly, in contrast to numerous clinically and preclinically used antibacterial photosensitizers, these compounds were able to eliminate various types of microorganisms, including Gram-(+) Staphylococcus aureus (S. aureus), Gram-(-) Escherichia coli, multidrug-resistant S. aureus, and their associated biofilms, at low drug and light dosages (e.g., 0.21 ng/mL in vitro and 1.63 ng/cm2 in vivo to eradicate S. aureus at 30 J/cm2). This study thus unveils the potential of these novel phenothiaziniums as potent antimicrobial agents for highly efficient photodynamic antibacterial chemotherapy.