Editorial: Antimicrobial Photodynamic Therapy: A New Paradigm in the Fight Against Infections

According to a 2019 report from the Center for Disease Control and Prevention (CDC), more than 2.8 million antibiotic-resistant infections occur in the U.S. each year, and more than 35, 000 people die as a result. This special issue is focused on Antimicrobial Photodynamic Therapy (PDT), which is a new strategy to fight against infections. PDT is mostly used in the treatment of cancer, and non-melanoma skin cancer is the most widely recognized indication. A photosensitizer that is activated by visible light in the presence of oxygen can generate reactive oxygen species resulting in the death of the microorganisms, without damaging the surrounding tissue. This innovative way of destroying microbial pathogens has many advantages compared with the conventional antimicrobials and antibiotics used so far. It has a broad spectrum of action, being able to kill or inactivate bacteria, fungi, viruses and protozoa..

In vitro effect of photodynamic therapy with different lights and combined or uncombined with chlorhexidine on Candida spp.

Candidiasis is very common and complicated to treat in some cases due to increased resistance to antifungals. Antimicrobial photodynamic therapy (aPDT) is a promising alternative treatment. It is based on the principle that light of a specific wavelength activates a photosensitizer molecule resulting in the generation of reactive oxygen species that are able to kill pathogens. The aim here is the in vitro photoinactivation of three strains of Candida spp., Candida albicans ATCC 10231, Candida parapsilosis ATCC 22019 and Candida krusei ATCC 6258, using aPDT with different sources of irradiation and the photosensitizer methylene blue (MB), alone or in combination with chlorhexidine (CHX). Irradiation was carried out at a fluence of 18 J/cm2 with a light-emitting diode (LED) lamp emitting in red (625 nm) or a white metal halide lamp (WMH) that emits at broad-spectrum white light (420–700 nm). After the photodynamic treatment, the antimicrobial effect is evaluated by counting colony forming units (CFU). MB-aPDT produces a 6 log10 reduction in the number of CFU/100 μL of Candida spp., and the combination with CHX enhances the effect of photoinactivation (effect achieved with lower concentration of MB). Both lamps have similar efficiencies, but the WMH lamp is slightly more efficient. This work opens the doors to a possible clinical application of the combination for resistant or persistent forms of Candida infections

Answer to photo quiz: Tunga penetrans

For both patients, considering the characteristics of the lesions, the epidemiological history of travel, and the microscopic study, a diagnosis of tungiasis was made. Tunga penetrans (sand flea) is a hematophagous flea 1 mm in length, whose habitat is warm, dry, sandy soils. This flea is widely distributed in parts of East and West Africa, South America, and the Caribbean and in countries bordering the Indian Ocean. This flea presents a wide range of wild and domestic hosts, humans being an accidental host. Occasionally, tourists from developed countries are diagnosed with tungiais after becoming infected in areas where the disease is endemic...

Photodynamic Therapy Combined with Antibiotics or Antifungals against Microorganisms That Cause Skin and Soft Tissue Infections: A Planktonic and Biofilm Approach to Overcome Resistances

The present review covers combination approaches of antimicrobial photodynamic therapy (aPDT) plus antibiotics or antifungals to attack bacteria and fungi in vitro (both planktonic and biofilm forms) focused on those microorganisms that cause infections in skin and soft tissues. The combination can prevent failure in the fight against these microorganisms: antimicrobial drugs can increase the susceptibility of microorganisms to aPDT and prevent the possibility of regrowth of those that were not inactivated during the irradiation; meanwhile, aPDT is effective regardless of the resistance pattern of the strain and their use does not contribute to the selection of antimicrobial resistance. Additive or synergistic antimicrobial effects in vitro are evaluated and the best combinations are presented. The use of combined treatment of aPDT with antimicrobials could help overcome the difficulty of fighting high level of resistance microorganisms and, as it is a multi-target approach, it could make the selection of resistant microorganisms more difficult

Association between preoperative levels of 25-hydroxyvitamin D and hospital-acquired infections after hepatobiliary surgery: A prospective study in a third-level hospital

Introduction Evidence implicates vitamin D deficiency in poorer outcomes and increased susceptibility to hospital-acquired infections (HAIs). This study examined the association between serum vitamin D levels and HAIs in a population of hepatobiliary surgery patients. Methods Participants in this prospective analytical observational study were patients who underwent hepatobiliary surgery in a tertiary hospital in Aragon, Spain, between February 2018 and March 2019. Vitamin D concentrations were measured at admission and all nosocomial infections during hospitalization and after discharge were recorded. Results The mean 25-hydroxyvitamin D concentration of the study population (n = 301) was 38.56 nmol/L, which corresponds to vitamin D deficiency. Higher vitamin D concentrations were associated with a decreased likelihood of developing a HAI in general (p = 0.014), and in particularly surgical site infection (p = 0.026). The risk of HAI decreased by 34% with each 26.2-nmol/L increase in serum vitamin D levels. Conclusions Vitamin D levels may constitute a modifiable risk factor for postoperative nosocomial infections in hepatobiliary surgery patients

Validation and Search of the Ideal Cut-Off of the Sysmex UF-1000i (R) Flow Cytometer for the Diagnosis of Urinary Tract Infection in a Tertiary Hospital in Spain

Urinary tract infections (UTI) are one of the most prevalent infections. A rapid and reliable screening method is useful to screen out negative samples. The objective of this study was to validate the Sysmex flow cytometer UF-1000i by evaluating its accuracy, linearity and carry-over; and define an optimal cut-off value to be used in routine practice in our hospital. For the validation of the UF-1000i cytometer, precision, linearity and carry-over were studied in samples with different counts of bacteria, leukocytes and erythrocytes. Between March and June 2016, urine samples were tested in the Clinical Microbiology Laboratory at University Miguel Servet Hospital, in Spain. Samples were analyzed with the Sysmex UF-1000i cytometer, and cultured. Growth of >= 10(5) CFUs/mL was considered positive. The validation study reveals that the precision in all the variables is acceptable; that there is a good linearity in the dilutions performed, obtaining values almost identical to those theoretically expected; and for the carry-over has practically null values. A total of 1, 220 urine specimens were included, of which 213 (17.4%) were culture positive. The optimal cut-off point of the bacteria-leukocyte combination was 138.8 bacteria or 119.8 leukocytes with an S and E of 95.3 and 70.4%, respectively. The UF-1000i cytometer is a valuable method to screen urine samples to effectively rule out UTI and, may contribute to the reduction of unnecessary urine cultures

Chalcogenide nanoparticles and organic photosensitizers for synergetic antimicrobial photodynamic therapy

Synergistic antimicrobial effects were observed for copper sulfide (CuS) nanoparticles together with indocyanine green (ICG) in the elimination of wild type pathogenic bacteria (Staphylococcus aureusATCC 29213 andPseudomonas aeruginosaATCC 27853) and also opportunistic fungal infective yeast (Candida albicansATCC 10231). Furthermore, large antibacterial effects were observed for clinical isolates of Methicillin-resistantS. aureus(MRSA) PFGE strain-type USA300. This efficient antimicrobial action was attributed to the combined extra- and intracellular generation of reactive oxygen species upon light irradiation. Instead of the use of visible-light for the activation of common photosensitizers, both ICG and CuS nanoparticles can be activated in the near infrared (NIR)-region of the electromagnetic spectrum and therefore, superior tissue penetration would be expected in a potential elimination of pathogenic microorganisms not only on the skin but also in the soft tissue. In the different bacteria studied a 3-log reduction in the bacterial counts was achieved after only 6 min of NIR irradiation and treatment with ICG or CuS alone at concentrations of 40 and 160 µg mL-1, respectively. A maximum bactericidal effect againstS. aureusand USA300 strains was obtained for the combination of both photosensitizers at the same concentration. RegardingP. aeruginosa, a 4-log reduction in the CFU was observed for the combination of CuS and ICG at various concentrations. InCandida albicansthe combination of both ICG and CuS and light irradiation showed an antimicrobial dose-dependent effect with the reduction of at least 3-log in the cell counts for the combination of ICG + CuS at reduced concentrations. The observed antimicrobial effect was solely attributed to a photodynamic effect and any photothermal effect was avoided to discard any potential thermal injury in a potential clinical application. The generation of reactive oxygen species upon near infrared-light irradiation for those photosensitizers used was measured either alone or in combination. The cytocompatibility of the proposed materials at the doses used in photodynamic therapy was also demonstrated in human dermal fibroblasts and keratinocytes by cell culturing and flow cytometry studies. © The Royal Society of Chemistry 2021

Daylight photodynamic therapy using methylene blue to treat sheep with dermatophytosis caused by Arthroderma vanbreuseghemii

Arthroderma vanbreuseghemii has been identified molecularly as the causative agent of dermatophytosis in a flock of sheep. It is necessary to explore new treatment alternatives because antifungals are not approved for use on small ruminant animals in the European Union. Antimicrobial photodynamic therapy (aPDT) has been shown to be effective for the treatment of dermatophytosis in humans. It is based on the application of a photosensitizer such as methylene blue (MB) that is activated by visible light to generate reactive oxygen species that are cytotoxic to cells. The use of daylight to perform aPDT (aDL-PDT) avoids the requirement of specific equipment because it uses sunlight to activate the photosensitizer. The aim of our study is to determine the efficacy of aDL-PDT using a 1% MB solution to treat dermatophytosis caused by A. vanbreuseghemii in ewes. Two different topical protocols (1% MB solution spray applications once or twice a week) were assayed in two groups of five infected animals. Twenty-five infected sheep were untreated. All the sheep were exposed to sunlight every day for an approximate duration of 10 h for a total of four weeks. At the end of the study, all the animals treated with aDL-PDT showed the same clinical response to both protocols. In contrast, the animals exposed only to sunlight required an additional two to four weeks before their infections resolved. Conclusion: aDL-PDT with 1% MB solution demonstrates efficacy, safety and efficiency in the treatment of dermatophytosis in sheep

Comparing Two Automated Techniques for the Primary Screening-Out of Urine Culture

Urinary tract infection is the most common human infection with a high morbidity. In primary care and hospital services, conventional urine culture is a key part of infection diagnosis but results take at least 24 h. Therefore, a rapid and reliable screening method is still needed to discard negative samples as quickly as possible and to reduce the laboratory workload. In this aspect, this study aims to compare the diagnostic performance between Sysmex OF-1000i and FUS200 systems in comparison to urine culture as the gold standard. From March to June 2016, 1, 220 urine samples collected at the clinical microbiology laboratory of the "Miguel Servet" hospital were studied in parallel with both analysers, and some technical features were evaluated to select the ideal equipment. The most balanced cut-off values taking into account bacteria or leukocyte counts were 138 bacteria/mu L or 119.8 leukocyte/pl for the OF-1000i (95.3% SE and 70.4% SP), and 5.7 bacteria/mu L or 4.3 leukocyte/mu L for the FUS200 (95.8% SE and 44.4% SP). The reduction of cultured plates was 37.4% with the FUS200 and 58.3% with the UF-1000i. This study shows that both techniques improve the workflow in the laboratory, but the OF-1000i has the highest specificity at any sensitivity and the FUS200 needs a shorter processing time

Comparison of Antibacterial Activity and Wound Healing in a Superficial Abrasion Mouse Model of Staphylococcus aureus Skin Infection Using Photodynamic Therapy Based on Methylene Blue or Mupirocin or Both

Background: Antibiotic resistance and impaired wound healing are major concerns in S. aureus superficial skin infections, and new therapies are needed. Antimicrobial photodynamic therapy (aPDT) is a new therapeutic approach for infections, but it also improves healing in many wound models. Objective: To compare the antimicrobial activity and the effects on wound healing of aPDT based on Methylene Blue (MB-aPDT) with mupirocin treatment, either alone or in combination, in superficial skin wounds of S. aureus-infected mice. Additionally, to evaluate the clinical, microbiological, and cosmetic effects on wound healing. Materials and Methods: A superficial skin infection model of S. aureus was established in SKH-1 mice. Infected wounds were treated with MB-aPDT, MB-aPDT with a daily topical mupirocin or only with mupirocin. No treatment was carried out in control animals. Daily clinical and microbiological examinations were performed until complete clinical wound healing. Histopathological studies and statistical analysis were performed at the end of the study. Results: MB-aPDT treatment induced the best wound healing compared to mupirocin alone or to mupirocin plus MB-aPDT. Superficial contraction at 24 h and a greater reduction in size at 48 h, quicker detachment of the crust, less scaling, and absence of scars were observed. Histopathological studies correlated with clinical and gross findings. By contrast, mupirocin showed the highest logaritmic reduction of S. aureus. Conclusions: MB-aPDT and mupirocin treatments are effective in a murine superficial skin infection model of S. aureus. One session of MB-aPDT was the best option for clinical wound healing and cosmetic results. The addition of mupirocin to MB-aPDT treatment improved antimicrobial activity; however, it did not enhance wound healing. No synergistic antibacterial effects were detected. © Copyright © 2021 Pérez, Robres, Moreno, Bolea, Verde, Pérez-Laguna, Aspiroz, Gilaberte and Rezusta