scholarly journals Photodynamic Therapy Is Effective Against Candida auris Biofilms

2021 ◽  
Vol 11 ◽  
Author(s):  
Priyanka S. Bapat ◽  
Clarissa J. Nobile
Keyword(s):  
Photodynamic Therapy ◽  
Fungal Infections ◽  
Red Light ◽  
Green Light ◽  
Multidrug Resistant ◽  
Antifungal Drug ◽  
Candida Auris ◽  
Human Fungal Pathogen ◽  
Drug Classes ◽  
Medical Need

Fungal infections are increasing in prevalence worldwide. The paucity of available antifungal drug classes, combined with the increased occurrence of multidrug resistance in fungi, has led to new clinical challenges in the treatment of fungal infections. Candida auris is a recently emerged multidrug resistant human fungal pathogen that has become a worldwide public health threat. C. auris clinical isolates are often resistant to one or more antifungal drug classes, and thus, there is a high unmet medical need for the development of new therapeutic strategies effective against C. auris. Additionally, C. auris possesses several virulence traits, including the ability to form biofilms, further contributing to its drug resistance, and complicating the treatment of C. auris infections. Here we assessed red, green, and blue visible lights alone and in combination with photosensitizing compounds for their efficacies against C. auris biofilms. We found that (1) blue light inhibited and disrupted C. auris biofilms on its own and that the addition of photosensitizing compounds improved its antibiofilm potential; (2) red light inhibited and disrupted C. auris biofilms, but only in combination with photosensitizing compounds; and (3) green light inhibited C. auris biofilms in combination with photosensitizing compounds, but had no effects on disrupting C. auris biofilms. Taken together, our findings suggest that photodynamic therapy could be an effective non-drug therapeutic strategy against multidrug resistant C. auris biofilm infections.

scholarly journals Photodynamic Therapy for 101 Early Cancers of the Upper Aerodigestive Tract, the Esophagus, and the Bronchi: A Single-Institution Experience

1999 ◽  
Vol 5 (3) ◽  
pp. 145-154 ◽  
Author(s):  
A. Radu ◽  
P. Grosjean ◽  
Ch. Fontolliet ◽  
G. Wagnieres ◽  
A. Woodtli ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Early Stage ◽  
Red Light ◽  
Green Light ◽  
Tracheobronchial Tree ◽  
Aerodigestive Tract ◽  
Upper Aerodigestive Tract ◽  
Photofrin Ii ◽  
Significant Difference ◽  
Radical Therapy

Cancer, when detected at an early stage, has a very good probability of being eradicated by surgery or radiotherapy. However, less aggressive treatments also tend to provide high rates of cure without the side effects of radical therapy. We report on the results of our clinical experience with photodynamic therapy (PDT) for the treatment of early carcinomas in the upper aerodigestive tract, the esophagus, and the tracheobronchial tree. Sixty-four patients with 101 squamous cell carcinomas were treated with three different photosensitizers: hematoporphyrin derivative (HPD), Photofrin II, and tetra (m-hydroxyphenyl)chlorin (mTHPC). Seventy-seven (76%) tumors showed a complete rsponse with no recurrence after a mean follow-up period of 27 months. There was no significant difference in terms of cure rates among the three dyes. However, mTHPC has a stronger phototoxicity and induces a shorter skin photosensitization than either of the other photosensitizers. There were eight major complications: three esophagotracheal fistulae after illumination with red light in the esophagus, two esophageal stenoses following 360° circumferential irradiation, and three bronchial stenoses. Illumination with the less penetrating green light and the use of a 180° or 240° windowed cylindrical light distributor render the risk of complications in the esophagus essentially impossible, without reducing the efficacy of the treatment. Therefore, PDT may be considered as a safe and effective treatment for early carcinomas of the upper aerodigestive tract, the esophagus, and the tracheobronchial tree.

Green light is effective and less painful than red light in photodynamic therapy of facial solar keratoses

1997 ◽  
Vol 13 (5-6) ◽  
pp. 181-185 ◽  
Author(s):  
C. Fritsch ◽  
H. Stege ◽  
G. Saalmann ◽  
G. Goerz ◽  
T. Ruzicka ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Red Light ◽  
Green Light

scholarly journals Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258465
Author(s):  
Mohamed Hagras ◽  
Nader S. Abutaleb ◽  
Ahmed M. Sayed ◽  
Ehab A. Salama ◽  
Mohamed N. Seleem ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
Fungal Infections ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Conformationally Restricted ◽  
Normal Human

To minimize the intrinsic toxicity of the antibacterial agent hydrazinyloxadiazole 1, the hydrazine moiety was replaced with ethylenediamine (compound 7). This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a conformationally-restricted isostere for ethylenediamine, potentiated the antifungal activity in both the cis and trans forms of N-(5-(2-([1,1’-biphenyl]-4-yl)-4-methylthiazol-5-yl)-1,3,4-oxadiazol-2-yl)cyclohexane-1,2-diamine (compounds 16 and 17). Both compounds 16 and 17 were void of any antibacterial activity; nonetheless, they showed equipotent antifungal activity in vitro to that of the most potent approved antifungal agent, amphotericin B. The promising antifungal effects of compounds 16 and 17 were maintained when assessed against an additional panel of 26 yeast and mold clinical isolates, including the Candida auris and C. krusei. Furthermore, compound 17 showed superior activity to amphotericin B in vitro against Candida glabrata and Cryptococcus gattii. Additionally, neither compound inhibited the normal human microbiota, and both possessed excellent safety profiles and were 16 times more tolerable than amphotericin B.

scholarly journals Fricke Dosimetry as a Tool to Quality Control of Photodynamic Therapy

2019 ◽  
Vol 7 (3) ◽  
Author(s):  
SUZANA OLIVEIRA SANTOS ◽  
Vivianne L. B. Souza
Keyword(s):  
Quality Control ◽  
Photodynamic Therapy ◽  
Low Cost ◽  
Red Light ◽  
Green Light ◽  
Yellow Light ◽  
Light Emitting ◽  
Low Toxicity ◽  
Cellular Necrosis ◽  
Photosensitizing Agent

Photodynamic therapy (PDT) consists of the association of a photosensitizing agent with a light source in order to cause cellular necrosis. Methylene blue, toluidine blue and malachite green are photosensitizers derived from dyes that are widely accepted in medicine, as they have low toxicity and are low cost. PDT is an alternative treatment for cancer, with significant advantages over procedures such as surgery/chemotherapy. Our laboratory has studied the Fricke solution doped with photosensitizers in an approach to obtain a quality control for PDT. The Fricke solution was prepared with ammoniacal ferrous sulfate, sodium chloride and sulfuric acid in water. The solutions modified with photosensitizers were prepared by adding 0.1 g/100 mL of the dyes. A volume of 2.6 ml of the Fricke solution modified with photosensitizers were transferred to test tubes and irradiated. The irradiated solutions had their optical densities measured in a spectrophotometer. The samples were irradiated with LED (Light Emitting Diodes) in acrylic phantoms. The FATA samples irradiated with LED showed the sensitivity of the dosimeters to red, blue, green and yellow light. A calibration curve with correlation coefficient of 0.9884 for the red light was obtained; 0.9752 for blue light; 0.9644 for the green light and 0.9768 for the yellow light. The fact that a sensitivity of the dosimeters to the LED has been occurred indicates that the PDT could be realized with LED, with lower costs than with laser. This work suggested that FATA dosimeters can be used for quality control of PDT.

scholarly journals Prevalence and Therapeutic Challenges of Fungal Drug Resistance: Role for Plants in Drug Discovery

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 150 ◽  
Author(s):  
Lewis Marquez ◽  
Cassandra L. Quave
Keyword(s):  
United States ◽  
Drug Resistance ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
The United States ◽  
Multidrug Resistant ◽  
Modern Medicine ◽  
Candida Auris ◽  
Medical Ethnobotany ◽  
Global Issue

Antimicrobial resistance is a global issue that threatens the effective practice of modern medicine and global health. The emergence of multidrug-resistant (MDR) fungal strains of Candida auris and azole-resistant Aspergillus fumigatus were highlighted in the Centers for Disease Control and Prevention’s (CDC) 2019 report, Antibiotic Resistance Threats in the United States. Conventional antifungals used to treat fungal infections are no longer as effective, leading to increased mortality. Compounding this issue, there are very few new antifungals currently in development. Plants from traditional medicine represent one possible research path to addressing the issue of MDR fungal pathogens. In this commentary piece, we discuss how medical ethnobotany—the study of how people use plants in medicine—can be used as a guide to identify plant species for the discovery and development of novel antifungal therapies.

scholarly journals In Vitro Activity of Manogepix against Multidrug-Resistant and Panresistant Candida auris from the New York Outbreak

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
YanChun Zhu ◽  
Shannon Kilburn ◽  
Mili Kapoor ◽  
Sudha Chaturvedi ◽  
Karen Joy Shaw ◽  
...  
Keyword(s):  
New York ◽  
Fungal Infections ◽  
Geometric Mean ◽  
Multidrug Resistant ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Wild Type ◽  
Candida Auris ◽  
Content Type

ABSTRACT An ongoing Candida auris outbreak in the New York metropolitan area is the largest recorded to date in North America. Laboratory surveillance revealed NY C. auris isolates are resistant to fluconazole, with variable resistance to other currently used broad-spectrum antifungal drugs, and that several isolates are panresistant. Thus, there is an urgent need for new drugs with a novel mechanism of action to combat the resistance challenge. Manogepix (MGX) is a first-in-class agent that targets the fungal Gwt1 enzyme. The prodrug fosmanogepix is currently in phase 2 clinical development for the treatment of fungal infections. We evaluated the susceptibility of 200 New York C. auris isolates to MGX and 10 comparator drugs using CLSI methodology. MGX demonstrated lower MICs than comparators (MIC50 and MIC90, 0.03 mg/liter; range, 0.004 to 0.06 mg/liter). The local epidemiological cutoff value (ECV) for MGX indicated all C. auris isolates were within the population of wild-type (WT) strains; 0.06 mg/liter defines the upper limit of wild type (UL-WT). MGX was 8- to 32-fold more active than the echinocandins, 16- to 64-fold more active than the azoles, and 64-fold more active than amphotericin B. No differences were found in the MGX or comparators’ MIC50, MIC90, or geometric mean (GM) values when subsets of clinical, surveillance, and environmental isolates were evaluated. The range of MGX MIC values for six C. auris panresistant isolates was 0.008 to 0.015 mg/liter, and the median and mode MIC values were 0.015 mg/liter, demonstrating that MGX retains activity against these isolates. These data support further clinical evaluation of fosmanogepix for the treatment of C. auris infections, including highly resistant isolates.

scholarly journals 1275. Evaluation of in vitro activity of manogepix against multidrug-resistant and pan-resistant Candida auris from the New York Outbreak

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S654-S654
Author(s):  
Yan Chun Zhu ◽  
Shannon N Kilburn ◽  
Mili Kapoor ◽  
Sudha Chaturvedi ◽  
Karen J Shaw ◽  
...  
Keyword(s):  
New York ◽  
Fungal Infections ◽  
Fungal Growth ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Candida Auris ◽  
Microsoft Excel ◽  
York Metropolitan Area ◽  
Clinical Surveillance

Abstract Background An ongoing Candida auris outbreak in the New York metropolitan area is the largest recorded to date in North America. NY C. auris isolates demonstrate resistance to fluconazole and variable resistance to other antifungals. Thus, there is an urgent need for new drugs with a novel mechanism of action to combat the resistance challenge. Manogepix (MGX) is a first-in-class agent that targets the fungal Gwt1 enzyme. The prodrug, fosmanogepix, is in clinical development for the treatment of invasive fungal infections. Methods We evaluated the susceptibility of 200 NY C. auris isolates (2017-2020) to MGX and 10 comparators. Testing was performed using TREK frozen broth microdilution panels for FLC, VRC, ITC, ISA, POS, AFG, CAS, and MFG. MGX MICs were evaluated (CLSI M27-A3 guidelines) using a 50% reduction in fungal growth endpoint at 24 h. MICs were determined by ETEST® at 24 h for AMB and FLC. We defined pan-resistant C. auris as isolates with in vitro resistance to two or more azoles, all echinocandins, and AMB. The epidemiological cutoff values (ECVs, ECOFFs) for MGX were estimated using the Microsoft Excel spreadsheet calculator ECOFFinder. Results MGX demonstrated lower MICs than comparators (MIC50 and MIC90 0.03 mg/L; range 0.004-0.06 mg/L). MGX was 8-32-fold more active that the echinocandins, 16-64-fold more active than the azoles, and 64-fold more active than AMB. No differences were found in the MGX or comparators’ MIC50, MIC90, or GEOMEAN values when subsets of clinical, surveillance, and environmental isolates were evaluated. The range of MGX MIC values for six C. auris pan-resistant isolates was 0.008-0.015 mg/L, and the median and mode MIC values were 0.015 mg/L, demonstrating that MGX retains activity against these isolates. The MGX epidemiological cutoff value (ECV, 99% cutoff) was 0.06 mg/L. Conclusion MGX MICs were low against C. auris isolates including those with variable patterns of resistance to AMB, azoles, and echinocandins. In addition, MGX retained potent activity against six pan-resistant isolates. These data support the continued clinical evaluation of fosmanogepix for the treatment of C. auris infections, including highly resistant isolates. Disclosures Karen J. Shaw, PhD, Amplyx (Consultant)Forge Therapeutics (Consultant) Vishnu Chaturvedi, PhD, Amplyx (Grant/Research Support)

scholarly journals Evaluation of in vitro activity of manogepix against multidrug-resistant and pan-resistant Candida auris from the New York Outbreak

2020 ◽  
Author(s):  
YanChun Zhu ◽  
Shannon Kilburn ◽  
Mili Kapoor ◽  
Sudha Chaturvedi ◽  
Karen Joy Shaw ◽  
...  
Keyword(s):  
New York ◽  
Fungal Infections ◽  
Multidrug Resistant ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Candida Auris ◽  
York Metropolitan Area ◽  
Clinical Surveillance ◽  
Laboratory Surveillance

ABSTRACTAn ongoing Candida auris outbreak in the New York metropolitan area is the largest recorded to date in North America. Laboratory surveillance revealed NY C. auris isolates are resistant to fluconazole, with variable resistance to other currently used broad-spectrum antifungal drugs, and that several isolates are pan-resistant. Thus, there is an urgent need for new drugs with a novel mechanism of action to combat the resistance challenge. Manogepix (MGX) is a first-in-class agent that targets the fungal Gwt1 enzyme. The prodrug, fosmanogepix, is currently in Phase 2 clinical development for the treatment of fungal infections. We evaluated the susceptibility of 200 New York C. auris isolates to MGX and 10 comparator drugs using CLSI methodology. MGX demonstrated lower MICs than comparators (MIC50 and MIC90 0.03 mg/L; range 0.004-0.06 mg/L). The MGX epidemiological cutoff value (ECV, 99% cutoff) for the tested C. auris isolates was 0.06 mg/L. MGX was 8-32-fold more active than the echinocandins, 16-64-fold more active than the azoles, and 64-fold more active than amphotericin B. No differences were found in the MGX or comparators’ MIC50, MIC90, or GEOMEAN values when subsets of clinical, surveillance, and environmental isolates were evaluated. The range of MGX MIC values for six C. auris pan-resistant isolates was 0.008-0.015 mg/L, and the median and mode MIC values were 0.015 mg/L, demonstrating that MGX retains activity against these isolates. These data support further clinical evaluation of fosmanogepix for the treatment of C. auris infections, including highly resistant isolates.

scholarly journals Photodynamic Therapy for Acinetobacter baumannii Burn Infections in Mice

2009 ◽  
Vol 53 (9) ◽  
pp. 3929-3934 ◽  
Author(s):  
Tianhong Dai ◽  
George P. Tegos ◽  
Zongshun Lu ◽  
Liyi Huang ◽  
Timur Zhiyentayev ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Acinetobacter Baumannii ◽  
Light Exposure ◽  
Middle Eastern ◽  
Red Light ◽  
Dorsal Surface ◽  
Multidrug Resistant ◽  
Dependent Manner ◽  
Chronic Infections ◽  
Bacterial Luminescence

ABSTRACT Multidrug-resistant Acinetobacter baumannii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment with traditional antibiotics can be extremely difficult, and new antimicrobial approaches are being investigated. One of these alternatives to antimicrobials could be the combination of nontoxic photosensitizers (PSs) and visible light, known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full-thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by the covalent conjugation of chlorin(e6) to polyethylenimine, followed by illumination of the burn surface with red light. Application of 108 A. baumannii cells to the surface of 10-s burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted, on average, 22 days and that were characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after application of the bacteria gave over 3 log units of loss of bacterial luminescence in a light exposure-dependent manner, while PDT carried out on day 1 and day 2 gave an approximately 1.7-log reduction. The application of PS dissolved in 10% or 20% dimethyl sulfoxide without light gave only a modest reduction in the bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to the inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multidrug-resistant localized A. baumannii infections.

scholarly journals Effective Photodynamic Inactivation of 26 Escherichia coli Strains with Different Antibiotic Susceptibility Profiles: A Planktonic and Biofilm Study

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 98 ◽  
Author(s):  
Òscar Gulías ◽  
Giselle McKenzie ◽  
Miquel Bayó ◽  
Montserrat Agut ◽  
Santi Nonell
Keyword(s):  
Escherichia Coli ◽  
Methylene Blue ◽  
Photodynamic Therapy ◽  
Reference Strain ◽  
Red Light ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antimicrobial Photodynamic Therapy ◽  
Strain Atcc

The emergence of multidrug-resistant bacteria is a growing problem and alternative therapies are being sought to effectively address this issue. The aim of this study is to assess a range of Escherichia coli strains’ susceptibility to Methylene Blue-mediated antimicrobial photodynamic therapy and determine if this is affected by their antibiotic-resistance profile. Two reference and twenty-four uropathogenic clinical E. coli strains were used in this study. All were tested in vitro for antimicrobial susceptibility against sixteen antibiotics. Strains underwent photodynamic treatments using the photosensitizer Methylene Blue with red light and tested in both planktonic and biofilm state. It was found that reference strain ATCC 25922 was susceptible to all tested antibiotics whereas reference strain ATCC 35218 showed resistance only to Ampicillin. With the exception of strains number 16 and 22, all of the isolated strains were multidrug-resistant according to the criteria established by the European Centre for Disease Prevention and Control and the Centre for Disease Control and Prevention, where acquired non-susceptibility to at least one agent in three or more antimicrobial categories is outlined. Photodynamic therapy induced more than 3 log10 colony-forming units’ reduction to all strains in planktonic state. Whereas when tested in biofilm state, two and a half times the original dose of methylene blue was necessary to cause a 3 log10 antimicrobial effect. There were statistically significant differences in susceptibility among the strains tested in both the planktonic and biofilm experiments. Nevertheless, antimicrobial photodynamic therapy could inactivate all multidrug-resistant strains in the planktonic and biofilm state.

Sign in / Sign up

Export Citation Format

Share Document