Antimicrobial resistance in Enterobacteriaceae : characterization and detection

De moleculaire karakterisering van antimicrobi_le resistentie mechanismen onderzocht in dit proefschrift toont de heterogeniteit aan van antimicrobi_le resistentiemechanismen in multiresistente Enterobacteriaceae. Naast de belangrijke overdraagbare ESBL-enzymen, CTX-M, SHV, TEM, plasmidaal gecodeerde AmpC _-lactamasen en carbapenemases zouden multiresistente isolaten in elk geval ook onderzocht moeten worden op de aanwezigheid van andere resistentie genen, zoals de plasmidaal-gemedieerde resistentie genen qnr en aac-6__-Ib-cr. Zoals beschreven in hoofdstuk 2, 3, en 4 is gebleken dat chromosomaal gecodeerde resistentie ook een belangrijke rol speelt. Hoewel verschillende technieken als multiplex PCR en sequentieanalyse, qRT-PCR en microarrays zijn gebruikt, is het gebruik hiervan niet toereikend om alle betrokken genen te kunnen onderzoeken. In het huidige tijdperk van multiresistente bacteri_n zijn moleculaire technieken nodig, die het hele genoom kunnen onderzoeken in __n test. De toepassing van next-generation sequencing (NGS) in een klinisch microbiologisch laboratorium zal alle informatie verstrekken: de identificatie van de species, de gevoeligheid voor antibiotica, de virulentie kenmerken en typering en tenslotte ook de hoeveelheid van de aanwezige species. Mogelijk kan NGS uiteindelijk de meeste, zo niet alle huidige fenotypische microbiologische methoden vervangen.Naast het gebruik van snelle en gevoelige detectie van resistentiemechanismen door niet-fenotypische testen, zal actieve realtime monitoring en surveillance belangrijker gaan worden.UBL - phd migration 201

Характеристика экономических отношений на финансовом рынке Украины

Розглянуто проблеми, особливості функціонування та взаємодії учасників фінансового ринку України. Обґрунтовано наявність внутрішніх фінансових джерел формування ресурсного потенціалу вітчизняних банків, доведено їх пріоритетність для країни порівняно із зовнішніми джерелами. Окреслено причини, що зумовлюють дефіцит ресурсного потенціалу в банківській системі України. Ключові слова: заощадження, нагромадження, банки, економічне зростання, посередники, фінансовий ринок, ресурси, трансформація, інвестиційний потенціал.Рассмотрены проблемы, особенности функционирования и взаимодействия участников финансового рынка Украины. Обосновано наличие внутренних финансовых источников формирования ресурсного потенциала отечественных банков, доказана их приоритетность для страны по сравнению с внешними источниками. Очерчены причины, которые предопределяют дефицит ресурсного потенциала в банковской системе Украины. Ключевые слова: сбережения, накопления, банки, экономический рост, посредники, финансовый рынок, ресурсы, трансформация, инвестиционный потенциал.The present paper examines topical problems related to the specific aspects of economic relations in the financial market of Ukraine. The relevance and selection of the theme stem from the fact that financial market as a specific organization form of cash flows takes a leading place in the economic mechanism of market economy. Agents of this market are engaged in a whole range of complex economic relations which in their turn play a key role in securing a dynamic and sustainable economic growth of a country. Development of the financial market and creation of adequate flexible and adaptive economic relations between its players are critical for Ukraine. This is explained by specific aspects of the economic system formation and reforming, which are related to undergoing an intersystem transformation stage. The indicated circumstances predetermined the goal and objectives of the study pursued, which come to examination of economic relations in the financial market of Ukraine, identification of the interaction specificity of various financial intermediaries in the accumulation process of idle cash and its transformation into the investment capital of national economy. Based on the results of the analysis conducted, it is established that unlike countries with developed financial systems, where the majority of institutional participants of the capital market are proportionally developed, it is the banking sector that dominates in Ukraine and has a determinant role in financing the economic development of the state. The availability of domestic financial resources for forming the resource potential of banks is substantiated, and their priority versus external resources for Ukraine is proved. The comparison of gross savings and gross capital formation allowed identifying certain problems as to transformation of the former into investment resources in Ukraine. The paper outlines some causes of a poor resource potential of national banking institutions. Keywords: savings, accumulation, banks, economic growth, intermediaries, financial market, resources, transformation, investment potential

Investigating the burden of antibiotic resistance in ethnic minority groups in high-income countries: protocol for a systematic review and meta-analysis.

BACKGROUND: Antibiotic resistance (ABR) is an urgent problem globally, with overuse and misuse of antibiotics being one of the main drivers of antibiotic-resistant infections. There is increasing evidence that the burden of community-acquired infections such as urinary tract infections and bloodstream infections (both susceptible and resistant) may differ by ethnicity, although the reasons behind this relationship are not well defined. It has been demonstrated that socioeconomic status and ethnicity are often highly correlated with each other; however, it is not yet known whether accounting for deprivation completely explains any discrepancy seen in infection risk. There have currently been no systematic reviews summarising the evidence for the relationship between ethnicity and antibiotic resistance or prescribing. METHODS: This protocol will outline how we will conduct this systematic literature review and meta-analysis investigating whether there is an association between patient ethnicity and (1) risk of antibiotic-resistant infections or (2) levels of antibiotic prescribing in high-income countries. We will search PubMed/MEDLINE, EMBASE, Global Health, Scopus and CINAHL using MESH terms where applicable. Two reviewers will conduct title/abstract screening, data extraction and quality assessment independently. The Critical Appraisal Skills Programme (CASP) checklist will be used for cohort and case-control studies, and the Cochrane collaboration's risk of bias tool will be used for randomised control trials, if they are included. Meta-analyses will be performed by calculating the minority ethnic group to majority ethnic group odds ratios or risk ratios for each study and presenting an overall pooled odds ratio for the two outcomes. The Grading of Recommendations, Assessments, Development and Evaluation (GRADE) approach will be used to assess the overall quality of the body of evidence. DISCUSSION: In this systematic review and meta-analysis, we will aim to collate the available evidence of whether there is a difference in rates of AMR and/or antibiotic prescribing in minority vs. majority ethnic groups in high-income countries. Additionally, this review will highlight areas where more research needs to be conducted and may provide insight into what may cause differences in this relationship, should they be seen. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ( CRD42016051533 )

Acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) carriage after exposure to systemic antimicrobials during travel: systematic review and meta-analysis

BACKGROUND: International travel is an important risk factor for colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Antimicrobial use during travel likely amplifies this risk, yet to what extent, and whether it varies by antimicrobial class, has not been established. METHODS: We conducted a systematic review that included prospective cohorts reporting both receipt of systemic antimicrobials and acquired ESBL-PE isolated from stool or rectum during international travel. We performed a random effects meta-analysis to estimate odds of acquiring ESBL-PE due to antimicrobials during travel, overall and by antimicrobial class. RESULTS: Fifteen studies were included. The study population was mainly female travellers from high income countries recruited primarily from travel clinics. Participants travelled most frequently to Asia and Africa with 10% reporting antimicrobial use during travel. The combined odds ratio (OR) for ESBL-PE acquisition during travel was 2.37 for antimicrobial use overall (95% confidence interval [CI], 1.69 to 3.33), but there was substantial heterogeneity between studies. Fluoroquinolones were the antibiotic class associated with the highest combined OR of ESBL-PE acquisition, compared to no antimicrobial use (OR 4.68, 95% CI, 2.34 to 9.37). CONCLUSIONS: The risk of ESBL-PE colonization during travel is increased substantially with exposure to antimicrobials, especially fluoroquinolones. While a small proportion of colonized individuals will develop a resistant infection, there remains the potential for onward spread among returning travellers. Public health efforts to decrease inappropriate antimicrobial usage during travel are warranted

Risk factors for fluoroquinolone-resistant Escherichia coli in adults with community-onset febrile urinary tract infection

Objectives To assess risk factors for fluoroquinolone resistance in community-onset febrile Escherichia coli urinary tract infection (UTI). Methods A nested case-control study within a cohort of consecutive adults with febrile UTI presenting at primary healthcare centres or emergency departments during January 2004 through December 2009. Resistance was defined using EUCAST criteria (ciprofloxacin MIC >1.0 mg/L). Cases were subjects with fluoroquinolone-resistant E. coli, and controls those with fluoroquinolone-susceptible isolates. Multivariable logistic regression analysis was used to identify potential risk factors for fluoroquinolone resistance. Results Of 787 consecutive patients, 420 had E. coli-positive urine cultures. Of these, 51 (12%) were fluoroquinolone resistant. Independent risk factors for fluoroquinolone resistance were urinary catheter [odds ratio (OR) 3.1; 95% confidence interval (CI) 0.9-11.6], recent hospitalization (OR 2.0; 95% CI 1.0-4.3) and fluoroquinolone use in the past 6 months (OR 17.5; 95% CI 6.0-50.7). Environmental factors (e.g. contact with animals or hospitalized household members) were not associated with fluoroquinolone resistance. Of fluoroquinolone-resistant strains, 33% were resistant to amoxicillin/clavulanate and 65% to trimethoprim/sulfamethoxazole; 14% were extended-spectrum β-lactamase (ESBL) positive compared with <1% of fluoroquinolone-susceptible isolates. Conclusions Recent hospitalization, urinary catheter and fluoroquinolone use in the past 6 months were independent risk factors for fluoroquinolone resistance in community-onset febrile E. coli UTI. Contact with animals or hospitalized household members was not associated with fluoroquinolone resistance. Fluoroquinolone resistance may be a marker of broader resistance, including ESBL positivity.Immunogenetics and cellular immunology of bacterial infectious disease

Clostridium difficile infection in an endemic setting in the Netherlands

The purpose of this investigation was to study risk factors for Clostridium difficile infection (CDI) in an endemic setting. In a 34-month prospective case–control study, we compared the risk factors and clinical characteristics of all consecutively diagnosed hospitalised CDI patients (n = 93) with those of patients without diarrhoea (n = 76) and patients with non-CDI diarrhoea (n = 64). The incidence of CDI was 17.5 per 10,000 hospital admissions. C. difficile polymerase chain reaction (PCR) ribotype 014 was the most frequently found type (15.9%), followed by types 078 (12.7%) and 015 (7.9%). Independent risk factors for endemic CDI were the use of second-generation cephalosporins, previous hospital admission and previous stay at the intensive care unit (ICU). The use of third-generation cephalosporins was a risk factor for diarrhoea in general. We found no association of CDI with the use of fluoroquinolones or proton pump inhibitors (PPIs). The overall 30-day mortality among CDI patients, patients without diarrhoea and patients with non-CDI diarrhoea was 7.5%, 0% and 1.6%, respectively. In this endemic setting, risk factors for CDI differed from those in outbreak situations. Some risk factors that have been ascribed to CDI earlier were, in this study, not specific for CDI, but for diarrhoea in general. The 30-day mortality among CDI patients was relatively high

Screening for multi-drug-resistant Gram-negative bacteria: what is effective and justifiable?

Effectiveness is a key criterion in assessing the justification of antibiotic resistance interventions. Depending on an intervention's effectiveness, burdens and costs will be more or less justified, which is especially important for large scale population-level interventions with high running costs and pronounced risks to individuals in terms of wellbeing, integrity and autonomy. In this paper, we assess the case of routine hospital screening for multi-drug-resistant Gram-negative bacteria (MDRGN) from this perspective. Utilizing a comparison to screening programs for Methicillin-Resistant Staphylococcus aureus (MRSA) we argue that current screening programmes for MDRGN in low endemic settings should be reconsidered, as its effectiveness is in doubt, while general downsides to screening programs remain. To accomplish justifiable antibiotic stewardship, MDRGN screening should not be viewed as a separate measure, but rather as part of a comprehensive approach. The program should be redesigned to focus on those at risk of developing symptomatic infections with MDRGN rather than merely detecting those colonised