Bactericidal Effect of Photodynamic Therapy, Alone or in Combination with Mupirocin or Linezolid, on Staphylococcus aureus

Antibiotic treatments frequently fail due to the development of antibiotic resistance, underscoring the need for new treatment strategies. Antimicrobial photodynamic therapy (aPDT) could constitute an alternative therapy. In bacterial suspensions of Staphylococcus aureus, which is commonly implicated in cutaneous and mucosal infections, we evaluated the in vitro efficacy of aPDT, using the photosensitizing agents rose bengal (RB) or methylene blue (MB), alone or combined with the antibiotics mupirocin (MU) or linezolid (LN). RB or MB, at concentrations ranging from 0.03 to 10 μg/ml, were added to S. aureus ATCC 29213 suspensions containing >108 cells/ml, in the absence or presence of MU or LN (1 or 10 μg/ml). Suspensions were irradiated with a white metal halide (λ 420–700 nm) or light-emitting diode lamp (λ 515 and λ 625 nm), and the number of viable bacteria quantified by counting colony-forming units (CFU) on blood agar. Addition of either antibiotic had no significant effect on the number of CFU/ml. By contrast, RB-aPDT and MB-aPDT effectively inactivated S. aureus, as evidenced by a 6 log10 reduction in bacterial growth. In the presence of MU or LN, the same 6 log10 reduction was observed in response to aPDT, but was achieved using significantly lower concentrations of the photosensitizers RB or MB. In conclusion, the combination of MU or LN and RB/MB-aPDT appears to exert a synergistic bactericidal effect against S. aureus in vitro

A combination of photodynamic therapy and antimicrobial compounds to treat skin and mucosal infections: A systematic review

Background: Antimicrobial photodynamic therapy (aPDT) is a growing approach to treat skin and mucosal infections. Despite its effectiveness, investigators have explored whether aPDT can be further combined with antibiotics and antifungal drugs. Objective: To systematically assess the in vivo studies on the effectiveness of combinations of aPTD plus antimicrobials in the treatment of cutaneous and mucosal infections. Materials and methods: Searches were performed in four databases (PubMed, EMBASE, Cochrane library databases, ClinicaTrials.gov) until July 2018. The pooled information was evaluated according to the PRISMA guidelines. Results: 11 full-text articles were finally evaluated and included. The best aPDT combinations involved 5-aminolevulinic acid or phenothiazinium dye-based aPDT. In general, the combination shows benefits such as reducing treatment times, lowering drug dosages, decreasing drug toxicity, improving patient compliance and diminishing the risk of developing resistance. The mechanism of action may be that first aPDT damages the microbial cell wall or membrane, which allows better penetration of the antimicrobial drug. Limitations: The number of studies was low, the protocols used were heterogeneous, and there was a lack of clinical trials. Conclusions: The additive or synergistic effect of aPDT combined with antimicrobials could be promising to manage skin and mucosal infections, helping to overcome the microbial drug resistance

Terapia fotodinámica antimicrobiana frente a agentes causantes de infecciones en piel y/o mucosas

Los microorganismos causantes de infecciones son cada vez más resistentes a los antibióticos. En este contexto, es necesaria la búsqueda de alternativas para combatirlos. La terapia fotodinámica antimicrobiana (TFDA) se presenta como una opción de tratamiento frente a los agentes causantes de infecciones en piel y/o mucosas. Es una modalidad terapéutica basada en la utilización de moléculas fotosensibilizantes que, al ser irradiadas con luz de una longitud de onda adecuada y a dosis suficiente, acaban generando especies reactivas de oxigeno que inducen la destrucción de las células diana. En la presente Tesis Doctoral, elaborada por compendio de publicaciones, se presentan seis Estudios que muestran cómo la TFDA es capaz de inactivar ciertas bacterias, levaduras y hongos filamentosos. Se han realizado experimentos con diferentes fotosensibilizantes clásicos, azul de metileno, rosa de bengala y curcumina y uno nuevo, probado por primera vez por nuestro grupo, con una estructura química cuyo núcleo está formado por seis átomos de molibdeno, logrando en todos los casos resultados prometedores. Además, se demuestra que se pueden usar distintos tipos de fuentes de luz para la aplicación de la TFDA habiéndose empleado satisfactoriamente lámparas LED, lámparas de halogenuro e incluso la luz solar. Asimismo, la TFDA en combinación con cada uno de los diferentes antibióticos ensayados, mupirocina, linezolid y gentamicina, ha mostrando efecto sinérgico en la inactivación de los microorganismos estudiados.<br /

Broad-spectrum photo-antimicrobial polymers based on cationic polystyrene and Rose Bengal

New strategies to fight bacteria and fungi are necessary in view of the problem of iatrogenic and nosocomial infections combined with the growing threat of increased antimicrobial resistance. Recently, our group has prepared and described two new readily available materials based on the combination of Rose Bengal (singlet oxygen photosensitizer) and commercially available cationic polystyrene (macroporous resin Amberlite® IRA 900 or gel-type resin IRA 400). These materials showed high efficacy in the antimicrobial photodynamic inactivation (aPDI) of Pseudomonas aeruginosa. Here, we present the photobactericidal effect of these polymers against an extended group of pathogens like Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, and the opportunistic yeast Candida albicans using green light. The most interesting finding is that the studied materials are able to reduce the population of both Gram-positive and Gram-negative bacteria with good activity, although, for C. albicans, in a moderate manner. In view of the results achieved and especially considering the inexpensiveness of these two types of photoactive polymers, we believe that they could be used as the starting point for the development of coatings for self-disinfecting surfaces

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Bactericidal Effect of Photodynamic Therapy, Alone or in Combination with Mupirocin or Linezolid, on Staphylococcus aureus

Antibiotic treatments frequently fail due to the development of antibiotic resistance, underscoring the need for new treatment strategies. Antimicrobial photodynamic therapy (aPDT) could constitute an alternative therapy. In bacterial suspensions of Staphylococcus aureus, which is commonly implicated in cutaneous and mucosal infections, we evaluated the in vitro efficacy of aPDT, using the photosensitizing agents rose bengal (RB) or methylene blue (MB), alone or combined with the antibiotics mupirocin (MU) or linezolid (LN). RB or MB, at concentrations ranging from 0.03 to 10 µg/ml, were added to S. aureus ATCC 29213 suspensions containing &gt; 108 cells/ml, in the absence or presence of MU or LN (1 or 10 µg/ml). Suspensions were irradiated with a white metal halide (¿ 420-700 nm) or light-emitting diode lamp (¿ 515 and ¿ 625 nm), and the number of viable bacteria quantified by counting colony-forming units (CFU) on blood agar. Addition of either antibiotic had no significant effect on the number of CFU/ml. By contrast, RB-aPDT and MB-aPDT effectively inactivated S. aureus, as evidenced by a 6 log10 reduction in bacterial growth. In the presence of MU or LN, the same 6 log10 reduction was observed in response to aPDT, but was achieved using significantly lower concentrations of the photosensitizers RB or MB. In conclusion, the combination of MU or LN and RB/MB-aPDT appears to exert a synergistic bactericidal effect against S. aureus in vitro

Bactericidal effect of photodynamic therapy, alone or in combination with mupirocin or linezolid, on Staphylococcus aureus

Antibiotic treatments frequently fail due to the development of antibiotic resistance, underscoring the need for new treatment strategies. Antimicrobial photodynamic therapy (aPDT) could constitute an alternative therapy. In bacterial suspensions of Staphylococcus aureus, which is commonly implicated in cutaneous and mucosal infections, we evaluated the in vitro efficacy of aPDT, using the photosensitizing agents rose bengal (RB) or methylene blue (MB), alone or combined with the antibiotics mupirocin (MU) or linezolid (LN). RB or MB, at concentrations ranging from 0.03 to 10 μg/ml, were added to S. aureus ATCC 29213 suspensions containing >108 cells/ml, in the absence or presence of MU or LN (1 or 10 μg/ml). Suspensions were irradiated with a white metal halide (λ 420–700 nm) or light-emitting diode lamp (λ 515 and λ 625 nm), and the number of viable bacteria quantified by counting colony-forming units (CFU) on blood agar. Addition of either antibiotic had no significant effect on the number of CFU/ml. By contrast, RB-aPDT and MB-aPDT effectively inactivated S. aureus, as evidenced by a 6 log10 reduction in bacterial growth. In the presence of MU or LN, the same 6 log10 reduction was observed in response to aPDT, but was achieved using significantly lower concentrations of the photosensitizers RB or MB. In conclusion, the combination of MU or LN and RB/MB-aPDT appears to exert a synergistic bactericidal effect against S. aureus in vitro

A photobleaching resistant polymer supported hexanuclear molybdenum iodide cluster for photocatalytic oxygenations and photodynamic inactivation of staphylococcus aureus

The ability of a hexanuclear molybdenum cluster, [Mo6I8(CH3COO)6]2-, to carry out, upon irradiation, singlet oxygen mediated photocatalytic oxygenation reactions has been tested. This complex has been also supported on a solid polymeric matrix, yielding an immobilized photosensitizer with remarkable photostability and recyclability. Preliminary studies of antibacterial photoinactivation of Staphylococcus aureus have been conducted, with positive results.The work at Universitat Jaume I was financially supported by Fundació Caixa Castelló/UJI (P1-1B2015-76). Technical assistance from the SCIC-UJI is acknowledged. M. M. thanks the Russian Foundation for Basic Research for research grant No. 16-33-60016. This study was also supported by grant CTQ2013-48767-C3-2-R from the Spanish Ministry of Science and Innovation, Spain and the European Regional Development Fund

Superior performance of macroporous over gel type polystyrene as a support for the development of photo-bactericidal materials

A hexanuclear molybdenum cluster [Mo6I8Ac6]2− (1) has been ionically bound onto macroporous (Pmp) and gel-type (Pgel) resins and their performance as materials for the photodynamic inactivation of microorganisms has been studied. It has been found that 1@Pmp in combination with light is able to reduce 99.999999% of the population of Gram-positive Staphylococcus aureus whereas the activity of 1@Pgel is limited to a 99.99% reduction at the same light dose. The same trend is observed with Gram-negative Pseudomonas aeruginosa. A comprehensive study of both materials has been performed using confocal laser scanning microscopy, thermogravimetric analysis, nitrogen porosimetry, steady state and time resolved fluorometries and diffuse reflectance spectroscopy. The photochemical generation of singlet oxygen (1O2) has been assessed using 9,10-dimethylanthracene as a trap for this reactive oxygen species. It can be concluded that the nature of the polymeric support is of paramount importance for the development of surfaces with bactericidal properties