Biofilms have been found to be involved in a wide variety of microbial infections in the body, by one estimate 80% of all infections. Infectious processes in which biofilms have been implicated ...include common problems such as urinary tract infections, catheter infections, middle-ear infections, sinusitis, formation of dental plaque, gingivitis, coating contact lenses, endocarditis, infections in cystic fibrosis, and infections of permanent indwelling devices such as joint prostheses and heart valves. Bacteria living in a biofilm usually have significantly different properties from free-floating bacteria of the same species, as the dense and protected environment of the film allows them to cooperate and interact in various ways. One benefit of this environment is increased resistance to detergents and antibiotics, as the dense extracellular matrix and the outer layer of cells protect the interior of the community. In some cases antibiotic resistance can be increased 1000-fold. Also, the biofilm bacteria excrete toxins that reversibly block important processes such as translation and protecting the cell from bactericidal antibiotics that are ineffective against inactive targets. In the head and neck area, biofilms are a major etiologic factor in periodontitis, wound infections, oral candidiasis, and sinus and ear infections. For the past several decades, photodynamic treatment has been reported in the literature to be effective in eradicating various microorganisms using different photosensitizers, different wavelengths of light, and different light sources. PDT has been further studied to demonstrate its effectiveness for the eradication of both Gram-negative and Gram-positive antibiotic-resistant bacteria. This chapter will focus on the use of PDT in the treatment of antibiotic-resistant biofilms, antibiotic-resistant wound infections, and azole-resistant oral candidiasis using methylene blue-based photodynamic therapy.
Photodynamic therapy (PDT) is a nonsurgical, minimally invasive treatment that uses a light source to activate light‐sensitive drugs or photosensitizers in the treatment of cancer and other diseases. ...PDT has been successfully employed to treat early carcinomas of the oral cavity and larynx preserving normal tissue and vital functions of speech and swallowing. Two hundred seventy‐six patients with early carcinomas of the oral cavity and larynx were treated from 1990 to 2006. Cure rates with a single treatment for early laryngeal and oral cancers were 91% and 94%, respectively. PDT is an effective primary and alternative treatment modality for early oral cavity and laryngeal cancers.
Background
To determine the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of a single cycle of RM-1929 photoimmunotherapy, an anti-EGFR antibody cetuximab conjugated with a ...light-activatable dye (IRDye
®
700DX), in Japanese patients with recurrent head and neck squamous cell carcinoma (rHNSCC).
Methods
Patients received a single fixed dose (640 mg/m
2
) of RM-1929 and a fixed light treatment dose (50 J/cm
2
for superficial illumination; 100 J/cm fiber diffuser length for interstitial illumination). Safety, tumor response (modified RECIST v1.1 by central radiology review), pharmacokinetics, and immunogenicity were evaluated.
Results
Three Japanese patients were enrolled who had failed ≥ 3 prior lines of therapy including radiation, chemotherapy, cetuximab, and immunotherapy. Target lesions were: submental lesion; right superficial cervical node lesion and oropharynx lesion; and external auditory canal lesion. All patients experienced ≥ 1 treatment-emergent adverse event (TEAE), but none were considered dose-limiting. TEAEs were mild to moderate in severity except for one grade 3 application-site pain, which was transient, resolved without sequelae within 24 h, and did not affect study treatment administration. Thirteen of 17 TEAEs reported were possibly or probably related to study treatment. Three patient reports of application-site pain and localized edema were deemed probably related to study treatment. Objective response was observed in two patients (both partial responses). The third patient had disease progression. RM-1929 concentrations and pharmacokinetic parameters were similar in all patients. No patients tested positive for anti-drug antibodies.
Conclusions
RM-1929 photoimmunotherapy showed a manageable safety profile in rHNSCC. Tumor response in these heavily pre-treated patients was clinically meaningful and warrants further investigation.
Clinical trial registration
The trial was registered with the Japanese registry of clinical trials as jRCT2031200133.
Navigation with fluorescence guidance has emerged in the last decade as a promising strategy to improve the efficacy of oncologic surgery. To achieve routine clinical use, the onus is on the surgical ...community to objectively assess the value of this technique. This assessment may facilitate both Food and Drug Administration approval of new optical imaging agents and reimbursement for the imaging procedures. It is critical to characterize fluorescence-guided procedural benefits over existing practices and to elucidate both the costs and the safety risks. This report is the result of a meeting of the International Society of Image Guided Surgery (www.isigs.org) on February 6, 2015, in Miami, Florida, and reflects a consensus of the participants' opinions. Our objective was to critically evaluate the imaging platform technology and optical imaging agents and to make recommendations for successful clinical trial development of this highly promising approach in oncologic surgery.
Objective
Methylene blue (MB) is a readily available and affordable substrate that can be used as a photosensitizer for photodynamic therapy (PDT). The objective of this study was to determine if PDT ...with MB can downregulate matrix metalloproteinases (MMPs) related to oral carcinoma.
Methods
Cell cultures of oral squamous cell carcinoma (CA‐9‐22), oral leukoplakia (MSK‐Leuk1), and immortalized keratinocytes (Rhek‐1A) were photosensitized with MB and treated with PDT. MMP‐9 gene expression was interrogated via qRT‐PCR. The 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay was used to confirm the efficacy of MB PDT.
Results
MMP‐9 gene expression was found to be significantly decreased in oral carcinoma, leukoplakia, and immortalized keratinocytes with use of MB PDT.
Conclusion
This work demonstrates that MB‐mediated PDT can downregulate MMPs which are critical to the invasion and metastasis of oral cancer. These results suggest that MB PDT could be a clinically significant and cost‐effective treatment for oral leukoplakia and carcinoma.
Level of Evidence
NA
This work demonstrates that methylene blue mediated photodynamic therapy (PDT) can downregulate matrix metalloproteinases which are critical to the invasion and metastasis of oral cancer by examining levels of gene expression and cell viability. These results suggest that methylene blue PDT could be a clinically significant and cost‐effective treatment for oral leukoplakia and carcinoma.
Chronic recurrent sinusitis (CRS) is an inflammatory disease of the facial sinuses and nasal passages that is defined as lasting longer than 12 weeks or occurring more than 4 times per year with ...symptoms usually lasting more than 20 days. The National Institute for Health Statistics estimates that CRS is one of the most common chronic conditions in the United States, affecting an estimated 37 million Americans. The potential etiologies of CRS include bacteria, viruses, allergies, fungi, superantigens, and microbial biofilms. In clinical practice there is a significant subpopulation of patients with CRS who remain resistant to cure despite rigorous treatment regimens including surgery, allergy therapy, and prolonged antibiotic therapy. The reason for treatment failure is thought to be related to the destruction of the sinus mucociliary defense by the chronic sinus infection resulting in the development of secondary antibiotic-resistant microbial colonization of the sinuses and biofilm formation. Antimicrobial photodynamic therapy (aPDT) is a nonantibiotic broad-spectrum antimicrobial treatment that has been demonstrated to eradicate antibiotic-resistant bacteria and biofilms. The objective of this study was to demonstrate the effectiveness of a noninvasive aPDT treatment method of eradicating antibiotic resistant biofilms/microorganisms known to cause CRS in an in vitro model.
Antibiotic-resistant planktonic bacteria and fungi and polymicrobial biofilms of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) were grown on silastic sheets and treated with a methylene blue photosensitizer and 670 nm non-thermal-activating light. Cultures of the planktonic microorganisms and biofilms were obtained before and after light treatment to determine efficacy of planktonic bacteria and biofilm reduction.
The in vitro CRS planktonic microorganism and biofilm study demonstrated that aPDT reduced the CRS polymicrobial biofilm by >99.9% after a single treatment.
aPDT can effectively treat CRS polymicrobial antibiotic-resistant bacteria, fungi, and biofilms in vivo. Human clinical studies are currently planned to assess the safety and efficacy of this treatment for CRS.
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