Evidence for wastewaters as environments where mobile antibiotic resistance genes emerge.

The emergence and spread of mobile antibiotic resistance genes (ARGs) in pathogens have become a serious threat to global health. Still little is known about where ARGs gain mobility in the first place. Here, we aimed to collect evidence indicating where such initial mobilization events of clinically relevant ARGs may have occurred.

Prognosis is worse with elevated cardiac troponin in nonacute coronary syndrome compared with acute coronary syndrome.

Background: Cardiac troponin (cTn) can be elevated in many patients presenting to the emergency department (ED) with chest pain but without a diagnosis of acute coronary syndrome (ACS). We compared the prognostic significance of cTn in these different populations.

Methods: We retrospectively analyzed the CHOPIN study, which enrolled patients who presented to the ED with chest pain.

Evidence for Pseudoxanthomonas mexicana as the recent origin of the bla carbapenemase gene.

Objectives: Elucidating the recent evolutionary history of clinically important antibiotic resistance genes may inform measures to delay the future emergence of additional resistance genes in clinics. This study investigated the recent origin of bla, a metallo-β-lactamase gene found in Pseudomonas aeruginosa, and the possible role of ISCR15 in its mobilisation and transfer into clinical species.

Methods: Comparative genomics were used to identify the recent origin of bla.

Large-scale characterization of the macrolide resistome reveals high diversity and several new pathogen-associated genes.

Macrolides are broad-spectrum antibiotics used to treat a range of infections. Resistance to macrolides is often conferred by mobile resistance genes encoding Erm methyltransferases or Mph phosphotransferases. New and genes keep being discovered in clinical settings but their origins remain unknown, as is the type of macrolide resistance genes that will appear in the future.

GEnView: a gene-centric, phylogeny-based comparative genomics pipeline for bacterial genomes and plasmids.

Summary: Comparing genomic loci of a given bacterial gene across strains and species can provide insights into their evolution, including information on e.g. acquired mobility, the degree of conservation between different taxa or indications of horizontal gene transfer events.

A framework for identifying the recent origins of mobile antibiotic resistance genes.

Since the introduction of antibiotics as therapeutic agents, many bacterial pathogens have developed resistance to antibiotics. Mobile resistance genes, acquired through horizontal gene transfer, play an important role in this process. Understanding from which bacterial taxa these genes were mobilized, and whether their origin taxa share common traits, is critical for predicting which environments and conditions contribute to the emergence of novel resistance genes.

Comprehensive screening of genomic and metagenomic data reveals a large diversity of tetracycline resistance genes.

Tetracyclines are broad-spectrum antibiotics used to prevent or treat a variety of bacterial infections. Resistance is often mediated through mobile resistance genes, which encode one of the three main mechanisms: active efflux, ribosomal target protection or enzymatic degradation. In the last few decades, a large number of new tetracycline-resistance genes have been discovered in clinical settings.

The Class A Carbapenemases BKC-1 and GPC-1 Both Originate from the Bacterial Genus .

Comparative genomics identified the environmental bacterial genus as the most likely origin of the class A carbapenemases BKC-1 and GPC-1. Available sequences and PCR analyses of additional species revealed homologous β-lactamases showing up to 85.4% and 93.

Selective concentrations for trimethoprim resistance in aquatic environments.

Antibiotic resistance presents a serious and still growing threat to human health. Environmental exposure levels required to select for resistance are unknown for most antibiotics. Here, we evaluated different experimental approaches and ways to interpret effect measures, in order to identify what concentration of trimethoprim that are likely to select for resistance in aquatic environments.

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction.

Background: The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers.

Long-term application of Swedish sewage sludge on farmland does not cause clear changes in the soil bacterial resistome.

The widespread practice of applying sewage sludge to arable land makes use of nutrients indispensable for crops and reduces the need for inorganic fertilizer, however this application also provides a potential route for human exposure to chemical contaminants and microbial pathogens in the sludge. A recent concern is that such practice could promote environmental selection and dissemination of antibiotic resistant bacteria or resistance genes. Understanding the risks of sludge amendment in relation to antibiotic resistance development is important for sustainable agriculture, waste treatment and infectious disease management.

Improve Management of acute heart failure with ProcAlCiTonin in EUrope: results of the randomized clinical trial IMPACT EU Biomarkers in Cardiology (BIC) 18.

Aim: To determine whether initiation of antibiotic therapy (ABX) by procalcitonin (PCT) within 8 h of admission in patients presenting to the emergency department with symptoms and signs of acute heart failure (AHF) and elevated natriuretic peptides would improve clinical outcomes.

Methods And Results: The study was a randomized multicentre clinical trial conducted at 16 sites in Europe. Patients were randomized to either a PCT-guided strategy or standard care.

The mobile FOX AmpC beta-lactamases originated in Aeromonas allosaccharophila.

Objective: It is important to understand the origins of antibiotic resistance genes so that risks associated with the emergence of novel resistance genes can be assessed and managed. The chromosomal ampC gene (CAV-1) of Aeromonas caviae (A. caviae) has been reported as the origin of mobile FOX cephalosporinases.

CMY-1/MOX-family AmpC β-lactamases MOX-1, MOX-2 and MOX-9 were mobilized independently from three Aeromonas species.

Objectives: To investigate the origin of CMY-1/MOX-family β-lactamases.

Methods: Publicly available genome assemblies were screened for CMY-1/MOX genes. The loci of CMY-1/MOX genes were compared with respect to synteny and nucleotide identity, and subjected to phylogenetic analysis.

PER extended-spectrum β-lactamases originate from Pararheinheimera spp.

To investigate the origin of PER extended-spectrum β-lactamases, publicly available sequence databases were searched for bla genes. Three genomes from Pararheinheimera, a genus associated with water and soil environments, were found to carry bla genes but lacked the ISCR1/ISPa12/ISPa13 insertion sequences commonly associated with bla in clinical isolates. Sequence analysis revealed 78-96% nucleotide identity and conserved synteny between the clinical mobile genetic elements (MGEs) encoding bla and the bla locus in the Pararheinheimera genomes.

Selective concentration for ciprofloxacin resistance in Escherichia coli grown in complex aquatic bacterial biofilms.

There is concern that antibiotics in the environment can select for and enrich bacteria carrying acquired antibiotic resistance genes, thus increasing the potential of those genes to emerge in a clinical context. A critical question for understanding and managing such risks is what levels of antibiotics are needed to select for resistance in complex bacterial communities. Here, we address this question by examining the phenotypic and genotypic profiles of aquatic communities exposed to ciprofloxacin, also evaluating the within-species selection of resistant E.

Rationale and design of the IMPACT EU-trial: improve management of heart failure with procalcitonin biomarkers in cardiology (BIC)-18.

Objectives: To evaluate the effectiveness of procalcitonin (PCT)-guided antibiotic treatment compared to current treatment practice to reduce 90-day all-cause mortality in emergency patients with shortness of breath (SOB) and suspected acute heart failure (AHF).

Background: Concomitant AHF and lower respiratory tract (or other bacterial) infection in emergency patients with dyspnea are common and can be difficult to diagnose. Early and adequate initiation of antibiotic therapy (ABX) significantly improves patient outcome, but superfluous prescription of ABX maybe harmful.

The Randomized Controlled STRAWINSKI Trial: Procalcitonin-Guided Antibiotic Therapy after Stroke.

Background: Pneumonia is among the most common acute complications after stroke and is associated with poor long-term outcome. Biomarkers may help identifying stroke patients at high risk for developing stroke-associated pneumonia (SAP) and to guide early treatment.

Aims: This trial investigated whether procalcitonin (PCT) ultrasensitive (PCTus)-guided antibiotic treatment of SAP can improve functional outcome after stroke.

Serial Procalcitonin Predicts Mortality in Severe Sepsis Patients: Results From the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study.

Objectives: To prospectively validate that the inability to decrease procalcitonin levels by more than 80% between baseline and day 4 is associated with increased 28-day all-cause mortality in a large sepsis patient population recruited across the United States.

Design: Blinded, prospective multicenter observational clinical trial following an Food and Drug Administration-approved protocol.

Setting: Thirteen U.

Postoperative pro-adrenomedullin levels predict mortality in thoracic surgery patients: comparison with Acute Physiology and Chronic Health Evaluation IV Score*.

Objectives: Risk assessment in ICU patients using commonly used prognostic models may be influenced using different data definitions and by errors in data collection. We investigated whether a set of biomarkers (procalcitonin, MR-pro-adrenomedullin, CT-pro-endothelin-1, CT-pro-arginine vasopressin, and MR-pro-atrial natriuretic peptide), alone or as a panel, could be useful in postoperative risk assessment for hospital mortality in comparison with the Acute Physiology and Chronic Health Evaluation IV score.

Design: In a prospective observational cohort study, we analyzed 800 consecutive patients undergoing elective cardiac surgery.

Predicting mortality and morbidity after elective cardiac surgery using vasoactive and inflammatory biomarkers with and without the EuroSCORE model.

Background: In cardiac surgery, preoperative mortality risk assessment tools like the EuroSCORE help to guide physicians in optimizing perioperative care of patients. We investigated the value of preoperative levels of inflammatory (procalcitonin [PCT]) and vasoactive (C-terminal pro-arginine vasopressin [CT-proAVP], midregional pro-atrial natriuretic peptide [MR-proANP], midregional proadrenomedullin [MR-proADM], and C-terminal pro-endothelin-1 [CT-proET-1]) biomarkers for risk assessment of mortality and morbidity and compared it with the EuroSCORE.

Methods: We performed a prospective observational cohort study in a single-center academic medical hospital and analyzed 746 consecutive patients undergoing elective cardiac surgery.

Plasma concentrations of the vasoactive peptide fragments mid-regional pro-adrenomedullin, C-terminal pro-endothelin 1 and copeptin in hemodialysis patients: associated factors and prediction of mortality.

Vasopressin, endothelin and adrenomedullin are vasoactive peptides that regulate vascular tone and might play a role in hypertensive diseases. Recently, laboratory assays have been developed to measure stable fragments of vasopressin, endothelin and adrenomedullin. Little is known about their diagnostic and prognostic value in hemodialysis patients.

Comparison of the performances of cardiac troponins, including sensitive assays, and copeptin in the diagnostic of acute myocardial infarction and long-term prognosis between women and men.

Background: Concerns have been raised about possible gender disparities in cardiac investigations and/or outcome. This study sought to examine and compare the diagnostic and prognostic performance of selected cardiac biomarkers in women versus men.

Methods: In a prospective, multicenter cohort of patients with acute chest pain cardiac troponin T (cTnT) (fourth-generation Roche assay), high-sensitivity cTnT (hs-cTnT), and copeptin were measured at presentation.

Copeptin helps in the early detection of patients with acute myocardial infarction: primary results of the CHOPIN trial (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction).

Objectives: The goal of this study was to demonstrate that copeptin levels <14 pmol/L allow ruling out acute myocardial infarction (AMI) when used in combination with cardiac troponin I (cTnI) <99 th percentile and a nondiagnostic electrocardiogram at the time of presentation to the emergency department (ED).

Background: Copeptin is secreted from the pituitary early in the course of AMI.

Methods: This was a 16-site study in 1,967 patients with chest pain presenting to an ED within 6 hours of pain onset.