Microbiota have emerged as key modulators of both the carcinogenic process and the immune response against cancer cells, and, thus, it seems to influence the efficacy of immunotherapy. While most ...studies have focused on analyzing the influence of gut microbiota, its composition substantially differs from that in the lung. Here, we describe how microbial life in the lungs is associated with host immune status in the lungs and, thus, how the identification of the microbial populations in the lower respiratory tract rather than in the gut might be key to understanding the lung carcinogenic process and to predict the efficacy of different treatments. Understanding the influence of lung microbiota on host immunity may identify new therapeutic targets and help to design new immunotherapy approaches to treat lung cancer.
Lungs are no longer considered sterile and their microbiota are associated with lung wellness.The lung microbiome has been linked to lung carcinogenesis and establishment of lung metastasis from other primary cancers.Lung microbiota dysbiosis may modulate the risk of malignancy at multiple levels including chronic inflammation and oncogenes.Patients treated with antibiotics before/during immunotherapy present with significantly lower progression-free survival and overall survival rates compared with patients who have not received antibiotics.Profiling of the gut microbiota revealed dysbiotic signatures associated with delayed tumor outgrowth and favorable responses to immunotherapy.
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.
To systematically assess the in vivo studies on the effectiveness of combinations of aPTD plus antimicrobials in the treatment of cutaneous and mucosal infections.
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.
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.
The number of studies was low, the protocols used were heterogeneous, and there was a lack of clinical trials.
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.
Abstract Introduction Antimicrobial resistance is currently one of the major public health threats. In order to prevent its spread, the WHO, OIE and FAO have formed an alliance to promote the study ...of antibiotic resistance evolution in human, animal and environmental bacteria posing a public health threat; however, the studies performed in wild animals are scarce so far. The main objective of this study was to assess the antibiotic resistance of Enterococcus spp. isolated from wild mammals in Aragón, Spain. Material and Methods Rectal samples were collected from 103 wild mammals – 70 hunt prey and 33 rescued animals. Isolates were identified by matrix-assisted laser desorption/ionisation–time of flight mass spectrometry and susceptibility tests to 10 antibiotics were also carried out. Statistical analysis was performed (P ≤ 0.05). Results A total of 126 isolates of seven different Enterococcus species were recovered. Among them, E faecalis (37.60%), E. casseliflavus (20.63%) and E. faecium (17.46%) were the most prevalent. The antibiotics quinupristin-dalfopristin and ciprofloxacin most frequently lost efficacy against the isolates. Multi-drug resistance was more prevalent in enterococci isolated from the rescued mammals. Conclusion This study found resistance widely distributed among enterococci isolated from the studied mammals. This points to the need for additional study of its genetic determinants and investigation of the sources and measures to avoid contributory environmental contamination.
Antimicrobial resistance is a global health threat. It has been studied in humans and domestic animals, but there is a lack of data on wild animals. The objective of this study is the elucidation of ...its patterns in
spp. isolated from wild mammals of the Autonomous Community of Aragón (Spain).
A total of 103 mammals (Artiodactyla, Carnivora, Chiroptera, Erinaceomorpha, and Lagomorpha) were studied. A recovery centre provided 32 and hunting 71. Nasal and faecal samples yielded 111 staphylococci, which were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. A susceptibility test to 11 antibiotics was carried out, and statistical analysis was performed.
Some differences were detected in bacterial prevalence depending on how the mammal fed. Artiodactyla, mainly hunted, were predisposed to carry coagulase-positive staphylococci. The staphylococci species recovered were resistant to at least two classes of antibiotics, and were disseminated in all of the geographical areas studied.
Resistant staphylococci are widely distributed in the wild mammals in the areas of the study, but the resistance quantified in them is lower than that to be expected if the use of antibiotics in farms had a direct influence on the wildlife and its environment. On the other hand, resistance to antibiotics restricted to human use was widely disseminated in various wild animal species.
Treatment of infections caused by multi-drug resistant (MDR) enterobacteria remains challenging due to the limited therapeutic options available. Drug repurposing could accelerate the development of ...new urgently needed successful interventions. This work aimed to identify and characterise novel drug combinations against Klebsiella pneumoniae based on the concepts of synergy and drug repurposing. We first performed a semi-qualitative high-throughput synergy screen (sHTSS) with tigecycline, colistin and fosfomycin (last-line antibiotics against MDR Enterobacteriaceae) against a FDA-library containing 1430 clinically approved drugs; a total of 109 compounds potentiated any of the last-line antibiotics. Selected hits were further validated by secondary checkerboard (CBA) and time-kill (TKA) assays, obtaining 15.09% and 65.85% confirmation rates, respectively. Accordingly, TKA were used for synergy classification based on determination of bactericidal activities at 8, 24 and 48 h, selecting 27 combinations against K. pneumoniae. Among them, zidovudine or azithromycin combinations with last-line antibiotics were further evaluated by TKA against a panel of 12 MDR/XDR K. pneumoniae strains, and their activities confronted with those clinical combinations currently used for MDR enterobacteria treatment; these combinations showed better bactericidal activities than usual treatments without added cytotoxicity. Our studies show that sHTSS paired to TKA are powerful tools for the identification and characterisation of novel synergistic drug combinations against K. pneumoniae. Further pre-clinical studies might support the translational potential of zidovudine- and azithromycin-based combinations for the treatment of these infections.
Synergistic antimicrobial effects were observed for copper sulfide (CuS) nanoparticles together with indocyanine green (ICG) in the elimination of wild type pathogenic bacteria (Staphylococcus aureus ...ATCC 29213 and Pseudomonas aeruginosa ATCC 27853) and also opportunistic fungal infective yeast (Candida albicans ATCC 10231). Furthermore, large antibacterial effects were observed for clinical isolates of Methicillin-resistant S. 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
, respectively. A maximum bactericidal effect against S. aureus and USA300 strains was obtained for the combination of both photosensitizers at the same concentration. Regarding P. aeruginosa, a 4-log reduction in the CFU was observed for the combination of CuS and ICG at various concentrations. In Candida albicans the 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.
To evaluate the effectiveness of the photodynamic therapy using hypericin (HYP) against both planktonic and biofilm-forming Staphylococcus aureus.
HYP photoactivity was evaluated against ...methicillin-susceptible and resistant S. aureus. Bacterial suspension or biofilm were preincubated with HYP and subjected to LED illumination. Viable bacteria were determined by colony counting.
Preincubation with HYP (5 min) plus light exposure (10 min) showed bactericidal effect against planktonic methicillin-susceptible S. aureus and methicillin-resistant S. aureus. Longer preincubation times (24 h) and time light exposure (30 min) were required to reach HYP-photoactivity against S. aureus biofilms. HYP-photoactivity was correlated to the biofilm production.
HYP could be a potential photosensitizer for the inactivation of staphylococcal biofilms forming on the surfaces accessible to visible light.
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.
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.
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.
Vitamin D levels may constitute a modifiable risk factor for postoperative nosocomial infections in hepatobiliary surgery patients.
Antimicrobial resistance is a worldwide problem that urges novel alternatives to treat infections. In attempts to find novel molecules, we assess the antimicrobial potential of seven essential oils ...(EO) of different plants (Pinus sylvestris, Citrus limon, Origanum vulgare, Cymbopogon martini, Cinnamomum cassia, Melaleuca alternifolia and Eucalyptus globulus) against two multidrug-resistant bacteria species, i.e. Neisseria gonorrhoeae and Streptococcus suis. EOs of P. sylvestris and C. limon revealed higher bactericidal activity (MIC ≤ 0.5 mg/mL) and capacity to rapidly disperse biofilms of several N. gonorrhoeae clinical isolates than other EOs. Examination of biofilms exposed to both EO by electron microscopy revealed a reduction of bacterial aggregates, high production of extracellular vesicles, and alteration of cell integrity. This activity was dose-dependent and was enhanced in DNase I-treated biofilms. Antibiotic susceptibility studies confirmed that both EOs affected the outer membrane permeability, and analysis of EO- susceptibility of an LPS-deficient mutant suggested that both EO target the LPS bilayer. Further analysis revealed that α- and β-pinene and d-limonene, components of both EO, contribute to such activity. EO of C. martini, C. cassia, and O. vulgare exhibited promising antimicrobial activity (MIC ≤ 0.5 mg/mL) against S. suis, but only EO of O. vulgare exhibited a high biofilm dispersal activity, which was also confirmed by electron microscopy studies. To conclude, the EO of P. sylvestris, C. limon and O. vulgare studied in this work exhibit bactericidal and anti-biofilm activities against gonococcus and streptococcus, respectively.
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•Essential oils of Pinus sylvestris and Citrus limon have bactericidal activity against drug-resistant Neisseria gonorrhoeae strains.•Essential oils of Pinus sylvestris and Citrus limon have high capacity to disperse gonococci biofilms.•α- and β-pinene and d-limonene are bioactive components of Essential oils of Pinus sylvestris and Citrus limon.•Essential oils of Origanum vulgare have bactericidal and biofilm dispersal activity against Streptococcus suis.
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