In vitro antibacterial activity of rhodanine derivatives against pathogenic clinical isolates

Bacterial infections present a serious challenge to healthcare practitioners due to the emergence of resistance to numerous conventional antibacterial drugs. Therefore, new bacterial targets and new antimicrobials are unmet medical needs. Rhodanine derivatives have been shown to possess potent antimicrobial activity via a novel mechanism. However, their potential use as antibacterials has not been fully examined. In this study, we determined the spectrum of activity of seven rhodanine derivatives (compounds Rh 1-7) against clinical isolates of Gram-positive and Gram-negative bacterial strains and Candida albicans. We also synthesized and tested three additional compounds, ethyl ester and amide of rhodanine 2 (Rh 8 and Rh 10, respectively) and ethyl ester of rhodanine 3 (Rh 9) to determine the significance of the carboxyl group modification towards antibacterial activity and human serum albumin binding. A broth microdilution assay confirmed Rh 1-7 exhibit bactericidal activity against Gram-positive pathogens. Rh 2 had significant activity against various vancomycin- resistant (MIC90 = 4 μM) and methicillin-resistant (MIC90 = 4 μM) Staphylococcus aureus (VRSA and MRSA), Staphylococcus epidermidis (MIC = 4 μM) and vancomycinresistant Enterococcus (VRE) strains (MIC90 = 8 μM). The rhodanine compounds exhibited potent activity against Bacillus spp., including Bacillus anthracis, with MIC range of 2-8 μM. In addition, they had potent activity against Clostridium difficile. The most potent compound, Rh 2, at 4 and 8 times its MIC, significantly decreased S. epidermidis biofilm mass by more than 35% and 45%, respectively. None of the rhodanine compounds showed antimicrobial activity (MIC \u3e 128 μM) against various 1) Gram-negative pathogens (Acinetobacter baumannii, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Salmonella Typhimurium) or 2) strains of Candida albicans (MIC \u3e 64 μM). The MTS assay confirmed that rhodanines were not toxic to mouse murine macrophage (J774.1A) up to 64 μM, human keratinocytes (HaCat) up to 32 μM, and human ileocecal colorectal cell (HRT-18) up to 128 μM. Overall, these data suggest that certain rhodanine compounds may have potential use for the treatment of several multidrug-resistant Gram-positive bacterial infections. © 2016 AbdelKhalek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

CXCL8 Chemokines in Teleost Fish: Two Lineages with Distinct Expression Profiles during Early Phases of Inflammation

Contains fulltext : 126584.pdf (publisher's version ) (Open Access

Search for flavor-changing neutral current interactions of the top quark and the Higgs boson decaying to a bottom quark-antiquark pair at root s=13 TeV

A search for flavor-changing neutral current interactions of the top quark (t) and the Higgs boson (H) is presented. The search is based on a data sample corresponding to an integrated luminosity of 137 fb(-1) recorded by the CMS experiment at the LHC in proton-proton collisions at root s = 13TeV. Events containing exactly one lepton (muon or electron) and at least three jets, among which at least two are identified as originating from the hadronization of a bottom quark, are analyzed. A set of deep neural networks is used for kinematic event reconstruction, while boosted decision trees distinguish the signal from the background events. No significant excess over the background predictions is observed, and upper limits on the signal production cross sections are extracted. These limits are interpreted in terms of top quark decay branching fractions (B) to the Higgs boson and an up (u) or a charm quark (c). Assuming one nonvanishing extra coupling at a time, the observed (expected) upper limits at 95% confidence level are B(t -> Hu) Hc) < 0.094 (0.086)%