1,166 research outputs found
The spread of CTX-M-type extended-spectrum B-lactamases
No full textCTX-M-type enzymes are a group of class A extended-spectrum beta-lactamases (ESBLs) that are rapidly spreading among Enterobacteriaceae worldwide. More that 50 allotypes are known, clustered into six sub-lineages. The CTX-M-encoding genes have been captured from the chromosome of Kluyvera spp. on conjugative plasmids that mediate their dissemination among pathogenic enterobacteria. CTX-M-type ESBLs exhibit powerful activity against cefotaxime and ceftriaxone but generally not against ceftazidime, which has important implications for laboratory detection. However, several CTX-M variants with enhanced ceftazidimase activity have been detected. The rapid and massive spread of CTX-M-type ESBLs is rapidly changing the ESBL epidemiology and, in some geographical areas, these enzymes are now the most prevalent ESBLs in Enterobacteriaceae
CTX-M-type β-lactamases: a successful story of antibiotic resistance
No full textProduction of extended-spectrum β-lactamases (ESBLs) is the principal mechanism of resistance to oxyimino-cephalosporins evolved by members of the family Enterobacteriaceae. Among the several ESBLs emerged among clinical pathogens, the CTX-M-type enzymes have proved the most successful in terms of promiscuity and diffusion in different epidemiological settings, where they have largely replaced and outnumbered other types of ESBLs. Originated by the capture and mobilization of chromosomal β-lactamase genes of strains of Kluyvera species, the blaCTX-M genes have become associated with a variety of mobile genetic elements that have mediated rapid and efficient inter-replicon and cell-to-cell dissemination involving highly successful enterobacterial lineages (e.g. Escherichia coli ST131 and ST405, or Klebsiella pneumoniae CC11 and ST147) to yield high-risk multiresistant clones that have spread on a global scale. The CTX-Mβ-lactamase lineage exhibits a striking plasticity, with a large number of allelic variants belonging in several sublineages, which can be associated with functional heterogeneity of clinical relevance. This review article provides an update on CTX-M-type ESBLs, with focus on structural and functional diversity, epidemiology and clinical significance. © 2013 Elsevier GmbH
Gli assetti proprietari degli operatori di private equity e la relazione con la performance delle aziende partecipate
No full textLa relazione peculiare che s’instaura tra azienda e private equity ha attirato l’attenzione di ricercatori e studiosi che, attraverso numerosi contributi, hanno analizzato l’impatto del private equity sulle aziende, confrontando la performance delle aziende venture backed rispetto a quella delle non venture backed. Il presente lavoro assume come già dimostrato, dalla letteratura nazionale e internazionale, il positivo contributo dell’investitore istituzionale all’azienda e si focalizza unicamente sul campione delle venture backed. Lo studio nasce dalla riflessione che calcolare la performance post IPO del gruppo delle venture backed company, senza effettuare distinzioni a seconda delle caratteristiche del private equity che partecipa l’azienda, possa essere un approccio eccessivamente generico. Per questo, si analizza la performance post IPO considerando la differente proprietà del private equity: bancaria o non bancaria. Nel dettaglio, il lavoro di tesi sviluppa l’analisi in riferimento al mercato italiano ed in particolare alle IPO di aziende venture backed realizzate nel periodo 1999-2006, proponendosi di verificare se la performance successiva alla quotazione delle aziende partecipate da private equity di proprietà bancaria sia significativamente differente da quella di aziende partecipate da operatori di proprietà non bancaria. L’analisi, sviluppata attraverso l’uso di differenti metodologie, evidenzia una differenza di performance a 6 mesi dalla quotazione, le venture backed partecipate da private equity non bancari realizzano una performance migliore di quelle participate da private equity bancari. Si ritiene, quindi interessante investigare quali potrebbero essere i motivi di tale diversità. In particolare si cerca di comprendere se questa sia imputabile principalmente alla scelta del private equity di investire in aziende con particolari caratteristiche di bilancio, a determinate scelte di gestione della partecipazione oppure a caratteristiche dell’investitore istituzionale. I private equity bancari rispetto ai non bancari tendono ad investire in aziende con un rapporto d’indebitamento maggiore, una capitalizzazione di mercato al momento della quotazione inferiore, detengono una minore quota di partecipazione dopo l’IPO, si caratterizzano per un maggior conflitto d’interesse e partecipano meno frequentemente come unico fondo. L’analisi successiva dimostra come, tra queste variabili, l’unica in grado di influenzare la performance a 6 mesi sia il rapporto d’indebitamento. Il lavoro di tesi identifica nell’indebitamento delle imprese la principale causa di diversità tra fondi bancari e non bancari: i fondi bancari si orientano verso imprese con un indebitamento maggiore e questo è uno dei motivi che possono contribuire a spiegare la peggiore performance dell’azienda nei 6 mesi successivi alla quotazione.The peculiar relationship established between a company and a private equity fund has attracted the attention of researchers and scholars who, through numerous contributions, have analyzed the impact of private equity on companies, comparing the performance of venture backed and non venture-backed companies.
This thesis accepts, as already demonstrated in national and international literature, the positive contribution of the institutional investor to the company, and it focuses solely on the sample of venture-backed companies. This research project comes to light from the reflection that calculating the post IPO performance of the venture backed company group, without making distinctions relative to the characteristics of the fund investing in the company, might prove to be too general an approach. For this reason, the post IPO performance is been analyzed, considering the different ownerships of the fund. The thesis proposes, in detail, an analysis of the Italian market; in particular, an analysis of the IPOs of venture backed companies made during the period ranging from 1999 to 2006. The aim is that of establishing whether the performance of companies with bank-owned private equity backing was significantly different from that of companies backed with non bank-owned funds, subsequent to listing on the Stock Exchange. The analysis is been carried out by using different methodologies: short- medium- and long-term performance after IPOs. Starting from the prior studies, the paper shows that there are significant differences in performance calculated for the entire time span under examination and in six-month performance after the IPO, where, companies with non-bank funds backing prove to have a better performance than those backed with bank-owned private equity. These findings drive to further the analysis in order to determine if the reasons of this difference correlate to particular features of the company’s balance sheet, or to particular private equity management rules of participation, or to specific private equity features.
The bank-owned private equity, compared to non-bank owned private equity, invests in companies with a higher leverage and a lower market capitalization at IPO time; it holds a lower percentage of capital after IPO, has a higher conflict of interest, and participates less frequently as the sole fund.
The last analysis demonstrates that the only variable that simultaneously distinguishes the two groups of companies, and influences the performance at 6-month time after IPO is the leverage. Bank-owned private equity invests in companies that have more debt than non bank-owned private equity; this is one of the reasons, which affects the lower company six-month performance after the IPO
Forthcoming therapeutic perspectives for infections due to multidrug-resistant Gram-positive pathogens
No full textMultidrug resistance in Gram-positive pathogens emerged as a major therapeutic challenge over two decades ago. The worldwide spread of methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci and other resistant Gram-positive pathogens had a major impact on antibiotic policies, and prompted the discovery and development of new antibiotics to combat difficult-to-treat infections caused by such pathogens. Several new antibiotics active against multidrug-resistant Gram-positive pathogens have recently been introduced into clinical practice, and the antibiotic pipeline contains additional anti-Gram-positive drugs at an advanced stage of development, including new glycopeptides (dalbavancin, oritavancin, and telavancin), new anti-MRSA beta-lactams (ceftobiprole), and new diaminopyrimidines (iclaprim). This article provides a brief overview of these upcoming agents, partially based on the material presented at the ESCMID Conference entitled 'Fighting infections due to multidrug-resistant Gram-positives' (Venice, Italy, 29-31 May 2008) and on the most recent literature
Coping with antibiotic resistance: contributions from genomics
No full textAntibiotic resistance is a public health issue of global dimensions with a significant impact on morbidity, mortality and healthcare-associated costs. The problem has recently been worsened by the steady increase in multiresistant strains and by the restriction of antibiotic discovery and development programs. Recent advances in the field of bacterial genomics will further current knowledge on antibiotic resistance and help to tackle the problem. Bacterial genomics and transcriptomics can inform our understanding of resistance mechanisms, and comparative genomic analysis can provide relevant information on the evolution of resistant strains and on resistance genes and cognate genetic elements. Moreover, bacterial genomics, including functional and structural genomics, is also proving to be instrumental in the identification of new targets, which is a crucial step in new antibiotic discovery programs
Intercontinental dissemination of IMP-13-producing Pseudomonas aeruginosa belonging in Sequence Type 621
No full textIMP-type metallo-β-lactamases (MBLs) were the first acquired MBLs detected in Gram-negative pathogens, in the early 1990s, and are among the most relevant due to their worldwide distribution.Fil: Santella, Gisela Natalia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Pollini, Simona. Universita Degli Studi Di Siena; ItaliaFil: Docquier, Jean-Denis. Universita Degli Studi Di Siena; ItaliaFil: Mereuta, Ana Irina. Universitatea de Medicina si Farmacie “Grigore T. Popa”; RumaniaFil: Gutkind, Gabriel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Rossolini, Gian Maria. Universita Degli Studi Di Siena; ItaliaFil: Radice, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin
From Pneumococcus to Pseudomonas: the antibacterial behaviour through the time [Dallo pneumococco alla Pseudomonas: Il comportamento antibatterico negli anni]
No full textThe worldwide use of fluoroquinolones in community and hospital settings, due to their high efficacy and tolerability, to the wide antibacterial spectrum and to the availability of an oral formulation, has created a relevant selective pressure for the emergence of resistant bacterial strains towards this antimicrobial class. Nevertheless, twenty years after development of the first fluoroquinolones (e.g. norfloxacin and ciprofloxacin) and ten years after levofloxacin introduction, the antibacterial activity of these drugs remains overall high
An Evidence-Based Multidisciplinary Approach Focused at Creating Algorithms for Targeted Therapy of BSIs, cUTIs, and cIAIs Caused by Enterobacterales in Critically Ill Adult Patients
No full textMilo Gatti,1,2 Bruno Viaggi,3 Gian Maria Rossolini,4– 6 Federico Pea,1,2 Pierluigi Viale1,7 1Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy; 2SSD Clinical Pharmacology, IRCCS Azienda Ospedaliero Universitaria Sant’Orsola, Bologna, Italy; 3Neurointensive Care Unit, Department of Anesthesiology, Careggi, University Hospital, Florence, Italy; 4Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; 5Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy; 6IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy; 7Infectious Diseases Unit, IRCCS Azienda Ospedaliero Universitaria Sant’Orsola, Bologna, ItalyCorrespondence: Federico PeaDepartment of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Massarenti, 9, Bologna, 40138, ItalyTel +39 051 214 3199Email [email protected]: Prompt implementation of appropriate targeted antibiotic therapy represents a valuable approach in improving clinical and ecological outcome in critically septic patients. This multidisciplinary opinion article focused at developing evidence-based algorithms for targeted antibiotic therapy of bloodstream (BSIs), complicated urinary tract (cUTIs), and complicated intrabdominal infections (cIAIs) caused by Enterobacterales. The aim was to provide a guidance for intensive care physicians either in appropriately placing novel antibiotics or in considering strategies for sparing the broadest-spectrum antibiotics. A multidisciplinary team of experts (one intensive care physician, one infectious disease consultant, one clinical microbiologist and one MD clinical pharmacologist), performed several rounds of assessment to reach agreement in developing six different algorithms according to the susceptibility pattern (one each for multi-susceptible, extended-spectrum beta-lactamase-producing, AmpC beta-lactamase-producing, Klebsiella pneumoniae carbapenemase (KPC)-producing, OXA-48-producing, and Metallo-beta-lactamase (MBL)-producing Enterobacterales). Whenever multiple therapeutic options were feasible, a hierarchical scale was established. Recommendations on antibiotic dosing optimization were also provided. In order to retrieve evidence-based support for the therapeutic choices proposed in the algorithms, a comprehensive literature search was performed by a researcher on PubMed-MEDLINE from inception until March 2021. Quality and strength of evidence was established according to a hierarchical scale of the study design. Only articles published in English were included. It is expected that these algorithms, by allowing prompt revision of antibiotic regimens whenever feasible, appropriate place in therapy of novel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and pharmacokinetic/pharmacodynamic optimization of antibiotic dosing regimens, may be helpful either in improving clinical outcome or in containing the spread of antimicrobial resistance.Keywords: critically ill patients, targeted antibiotic therapy, antimicrobial stewardship, Enterobacterales, multidisciplinary taskforce, PK/PD dosing optimizatio
A new asset allocation technique to reduce financial portfolio risk
No full textThe objective of this work is to illustrate an active portfolio management methodology reducing the risk of the portfolio through stabilization of returns, by applying the proportional, integral, derivative (PID) control on the pure portfolio return variable. Two portfolios are analyzed and their financial performance is compared: the PID methodology implementation yielding the experimental portfolio on one side, and its corresponding benchmark, the DJ Euro Stoxx 50 Index on the other side. The experimental portfolio is able to diminish the volatility, and in particular, to accomplish a smaller down side risk than its corresponding benchmark
- …
