1,720,963 research outputs found
Antimicrobial and antibiofilm activity of drug combinations and violet-blue light against clinically relevant bacterial pathogens causing airway infections
Full text linkPseudomonas aeruginosa, Stenotrophomonas maltophilia and Staphylococcus aureus lung colonization is critical in cystic fibrosis (CF) and other chronic lung diseases, contributing to disease progression. Biofilm growth and a propensity to evolve multidrug resistance phenotypes drastically limit the available therapeutic options. In this perspective, there has been growing interest in evaluating both combination therapies, especially for drugs administrable by nebulization allowing to achieve high lung concentrations while reducing systemic toxicity, and non-antibiotic therapies based on the using of visible light capable of generating reactive oxygen species leading to bacterial killing.
In this doctoral thesis, the potential synergism of N-acetylcysteine (NAC) (a mucolytic agent with antioxidant and anti-inflammatory properties) in combination with colistin (among the last-resort agents for the treatment of infections caused by multidrug resistant Gram-negative bacteria) against S. maltophilia grown in planktonic and biofilm phase, and P. aeruginosa biofilms was investigated. The transcriptomic response of a P. aeruginosa CF strain to NAC exposure was also studied. A wide collection of S. maltophilia and P. aeruginosa clinical isolates (comprising strains isolated from CF patients and colistin-resistant strains) was included in the study. On the other hand, the potential in vitro activity of violet-blue light (415 nm wavelength) against planktonic and biofilm cultures of P. aeruginosa and S. aureus strains (including strains isolated from CF patients) was investigated. The potentiation of the antimicrobial activity of light at 415 nm in the presence of potassium iodide (KI) against planktonic cultures was also evaluated. The latter investigations were part of the follow-up activities of the European project Light4Lungs aimed at develops a novel antimicrobial therapy for the treatment of chronic lung infections using inhalable light sources.
Checkerboard assays carried out with S. maltophilia strains showed a synergism of NAC-colistin combinations against the strains exhibiting colistin Minimum Inhibitory Concentration (MIC) >2 mg/L (n=13), suggesting that NAC could antagonize the mechanisms involved in colistin resistance. Nonetheless, time-kill assays revealed that NAC might potentiate colistin activity also in case of lower colistin MICs. A dose-dependent potentiation of colistin activity by NAC was clearly observed against S. maltophilia biofilms, also at sub-MIC concentrations. Biofilm susceptibility testing performed against P. aeruginosa showed a limited and strain-dependent antibiofilm activity of NAC alone (8,000 mg/L). However, a relevant antibiofilm synergism of NAC-colistin combinations was observed with the majority of the P. aeruginosa strains tested. Synergism was also confirmed with the artificial sputum medium model. RNA sequencing of NAC-exposed planktonic cultures revealed that NAC (8,000 mg/L) mainly induced (i) a Zn2+ starvation response (known to induce attenuation of P. aeruginosa virulence), (ii) downregulation of genes of the denitrification apparatus, and (iii) downregulation of flagellar biosynthesis pathway. NAC-mediated inhibition of P. aeruginosa denitrification pathway and flagellum-mediated motility were confirmed experimentally. A potential antimicrobial activity of the light at 415 nm against all the tested strains (n=4) was observed. A dose-dependent effect was detected against P. aeruginosa strains grown in planktonic phase, while only a scant or no effect was observed against S. aureus cultures. Nevertheless, the addition of KI to the planktonic cultures potentiated the photokilling activity of 415 nm LED light leading to eradication of starting inocula in three out of four cases, confirming the involvement of KI in the bacterial cell death. An antibiofilm activity of the light at 415 nm was observed against both P. aeruginosa strains and S. aureus strains, with the major effects evident against clinical isolates compared to the reference strains, underlining the differences of response to oxidative stress between diverse physiological states of growth.
NAC-colistin combinations, at concentrations likely achievable by topical administration, might represent a valid option for the treatment of infections caused by biofilm-associated pathogens, such as S. maltophilia and P. aeruginosa, while potentially reducing the risk of in vivo selection of colistin resistance. NAC might also have a role in reducing P. aeruginosa virulence, which could be relevant in the very early stages of lung colonization. The antibiofilm activity of violet-blue light would deserve further investigation to consolidate the obtained data for the potential clinical application of this approach, especially in biofilm-associated chronic infections. The potentiation of photokilling activity of antimicrobial light mediated by KI should be further examined
Multidrug-Resistant Bacteria Contaminating Plumbing Components and Sanitary Installations of Hospital Restrooms
No full textAntimicrobial resistance (AMR) poses several issues concerning the management of hospital-acquired infections, leading to increasing morbidity and mortality rates and higher costs of care. Multidrug-resistant (MDR) bacteria can spread in the healthcare setting by different ways. The most important are direct contact transmission occurring when an individual comes into physical contact with an infected or colonized patient (which can involve healthcare workers, patients, or visitors) and indirect contact transmission occurring when a person touches contaminated objects or surfaces in the hospital environment. Furthermore, in recent years, toilets in hospital settings
have been increasingly recognised as a hidden source of MDR bacteria. Different sites in restrooms, from toilets and hoppers to drains and siphons, can become contaminated with MDR bacteria that
can persist there for long time periods. Therefore, shared toilets may play an important role in the transmission of nosocomial infections since they could represent a reservoir for MDR bacteria. Such
pathogens can be further disseminated by bioaerosol and/or droplets potentially produced during toilet use or flushing and be transmitted by inhalation and contact with contaminated fomites. In this review, we summarize available evidence regarding the molecular features of MDR bacteria contaminating toilets of healthcare environments, with a particular focus on plumbing components and sanitary installation. The presence of bacteria with specific molecular traits in different toilet sites should be considered when adopting effective managing and containing interventions against nosocomial infections potentially due to environmental contamination. Finally, here we provide an
overview of traditional and new approaches to reduce the spreading of such infections
Activity of a foam in preventing rebound of vancomycin-resistant Enterococcus faecium-containing droplets generated from the toilet bowl
No full textIn hospital environments, droplets generated by urination within shared toilets may represent a route of dissemination for bacteria such as vancomycin-resistant Enterococcus faecium (VREfm), which contributes significantly to the burden of hospital-acquired infections. We investigated the potential activity of a foam in preventing the generation of droplets containing Enterococcus spp. during urination. A uniform layer of foam was deposited in the inner walls and at the bottom of an experimental toilet contaminated with suspensions of Enterococcus strains (including a VREfm strain). Human urination was simulated, and colonies of Enterococcus were recovered through a toilet lid where agar plates had been placed. Results showed that the foam was able to suppress production of droplets containing Enterococcus spp. generated by a liquid hitting inner toilet walls. Conversely, Enterococcus colonies were recovered in absence of foam. Moreover, the foam did not show antibacterial activity. We propose a new non-antimicrobial approach aimed at limiting transmission of multidrug-resistant bacteria, particularly in healthcare settings
The Y58D mutation in rpsJ gene is correlated with tigecycline and eravacycline combined resistance in ST80 vancomycin-resistant Enterococcus faecium isolates
No full textObjectives: To describe the phenotypic and genetic features of vancomycin-resistant Enterococcus faecium (VREfm) isolates exhibiting resistance to tetracycline (TET), tigecycline (TGC) and eravacycline (ERV). Methods: Between December 2023 and September 2024, 32 vancomycin-resistant Enterococci (VRE) were collected from clinical samples at the Policlinico Foggia, Italy. Bacterial identification was carried out by mass spectrometry analysis (MALDI-TOF). Antimicrobial susceptibility testing for vancomycin (VA), TET, TGC and ERV was performed by reference broth microdilution method. Whole-genome sequencing (WGS) was carried out to explore the content of tetracyclines resistance determinants, and the phylogenetic relationship between isolates (in silico MLST and SNPs analysis). Results: Among studied isolates, thirty and two were E. faecium and Enterococcus faecalis (Efs), respectively. Overall, eight isolates, six VREfm and two VREfs, were resistant to TET (8/32, 25%), with four (all VREfm) being resistant to TGC and ERV (4/32, 12.5%), also. The two TET-resistant VREfs strains belonged to ST6 and carried the tet(M) gene only. All the TET-resistant VREfm were ST80 and carried tet(L) and tet(M) genes. Among these, the four TGC-resistant and ERV-resistant strains showed an uncommon Y58D substitution in the ribosomal S10 protein (rpsJ gene). SNPs analysis revealed that Y58D-carrying strains formed a separate cluster, within ST80 VREfm. Conclusions: In this study we correlated the presence of the Y58D mutation in the rpsJ gene with resistance to TGC and ERV in a cluster of VREfm ST80 clinical strains. The Y58D mutation was invariably found in co-presence with tet(L) and tet(M) genes
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Prevalence of Blastocystis sp. and other gastrointestinal pathogens among diarrheic COVID-19 patients in Italy
No full textBackgroundGastrointestinal pathogens (GPs) contribute significantly to the burden of illness worldwide with diarrhoea being the most common among gastrointestinal symptoms (GSs). In the COVID-19 disease, diarrhoea, could be one of the initial presenting symptoms. However, no data on the potential correlation between diarrhoea-causing pathogens and SARS-CoV-2 infection are available. Therefore, we carried out a 2-years retrospective study aimed to evaluate the prevalence of “classic” GPs among SARS-CoV-2 infected and non-infected patients with diarrhoea in Italy. MethodsResults of SARS-CoV-2 research from nasopharyngeal and detection of GPs from stool swab samples by Allplex™ SARS-CoV-2 and GI Virus, Bacteria and Parasite Assay were analysed for all patients with diarrhoea referring to Policlinico Ospedaliero Universitario, Foggia, (Italy) from February 2022 to October 2023. ResultsOut of the 833 involved patients, 81 (3.9%) were COVID-19 positive, while 752 (90.3%) were COVID-19 negative. Among COVID-19-positive patients, 37% (n = 30/81) were found positive for one or more GPs with a higher prevalence of protozoan parasites (18.5%) (Blastocystis ST1-ST4 subtypes, Dientamoeba fragilis genotype I), followed by bacteria (7.4%) (Campylobacter sp., Salmonella sp.). Viral pathogens were more frequent among COVID-19 negative patients (Adenovirus, Norovirus). Among GPs, Blastocystis ST3 subtype was the most prevalent registered in the 16% of patients (p = 0.0001). ConclusionsBased on obtained results, a likely interaction between the classic GPs and SARS-CoV-2 infection can be speculated, driven by protozoan parasites. Moreover, these results also provide baseline data to understand more deeply Blastocystis sp. role in this scenario of dysbiosis, particularly in those cases of SARS-CoV-2 co-infection
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Activity of N-Acetylcysteine Alone and in Combination with Colistin against Pseudomonas aeruginosa Biofilms and Transcriptomic Response to N-Acetylcysteine Exposure
No full textChronic colonization by Pseudomonas aeruginosa is critical in cystic fibrosis (CF) and other chronic lung diseases, contributing to disease progression. Biofilm growth and a propensity to evolve multidrug resistance phenotypes drastically limit the available therapeutic options. In this perspective, there has been growing interest in evaluating combination therapies, especially for drugs that can be administered by nebulization, which allows high drug concentrations to be reached at the site of infections while limiting systemic toxicity. Here, we investigated the potential antibiofilm activity of N-acetylcysteine (NAC) alone and in combination with colistin against a panel of P. aeruginosa strains (most of which are from CF patients) and the transcriptomic response of a P. aeruginosa CF strain to NAC exposure. NAC alone (8,000 mg/L) showed a limited and strain-dependent antibiofilm activity. Nonetheless, a relevant antibiofilm synergism of NAC-colistin combinations (NAC at 8,000 mg/L plus colistin at 2 to 32 mg/L) was observed with all strains. Synergism was also confirmed with the artificial sputum medium model. RNA sequencing of NAC-exposed planktonic cultures revealed that NAC (8,000 mg/L) mainly induced (i) a Zn(2+) starvation response (known to induce attenuation of P. aeruginosa virulence), (ii) downregulation of genes of the denitrification apparatus, and (iii) downregulation of flagellar biosynthesis pathway. NAC-mediated inhibition of P. aeruginosa denitrification pathway and flagellum-mediated motility were confirmed experimentally. These findings suggested that NAC-colistin combinations might contribute to the management of biofilm-associated P. aeruginosa lung infections. NAC might also have a role in reducing P. aeruginosa virulence, which could be relevant in the very early stages of lung colonization. IMPORTANCE Pseudomonas aeruginosa biofilm-related chronic lung colonization contributes to cystic fibrosis (CF) disease progression. Colistin is often a last-resort antibiotic for the treatment of such P. aeruginosa infections, and it has been increasingly used in CF, especially by nebulization. N-acetylcysteine (NAC) is a mucolytic agent with antioxidant activity, commonly administered with antibiotics for the treatment of lower respiratory tract infections. Here, we show that NAC potentiated colistin activity against in vitro biofilms models of P. aeruginosa strains, with both drugs tested at the high concentrations achievable after nebulization. In addition, we report the first transcriptomic data on the P. aeruginosa response to NAC exposure
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