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La resistenza agli antibiotici in Pseudomonas aeruginosa: studio molecolare ed epidemiologico in un nosocomio marchigiano
Full text linkAntibiotico-resistenza a Pseudomonas aeruginosa: studio molecolare ed epidemiologico in un ospedale marchigiano.
Negli ultimi anni P.aeruginosa è diventato uno dei microrganismi più resistenti ai farmaci. Nonostante l'introduzione di nuovi antibiotici come Ceftolozane/tazobactam (C/T), una nuova combinazione di inibitori della cefalosporina/β-lattamasi con una potente attività contro gli isolati di Pseudomonas aeruginosa, sono stati riportati diversi isolati di P. aeruginosa resistenti.Antibiotic resistance in Pseudomonas aeruginosa: molecular and epidemiological study in a hospital in the Marche region
Background: In the last years P.aeruginosa has became one of most drug resistant microorganism. Despite introduction of new antibiotics such as Ceftolozane/tazobactam (C/T), a novel cephalosporin/β-lactamase inhibitor combination with a potent activity against Pseudomonas aeruginosa isolates, several resistant P. aeruginosa isolates have been reported. From November 2016 to April 2019 we performed both a retrospective study on C/T prescriptions and activity both a survey on clinical strains of P. aeruginosa isolated at “Ospedali Riuniti” of Ancona, Italy, characterising the resistant isolates.
Materials/methods: From November 2016 to April 2019 we have collected data about C/T activity and efficacy against all multidrug resistant gram negative isolated at Ospedali Riuniti of Ancona. Particularly we have studied activity of C/T against P.aeruginosa, and microbiological and genetic charateristics of this microorganism. MICs to C/T were determined with gradient test for all P. aeruginosa recovered at the clinical laboratory of “Ospedali Riuniti” from October 2018 to March 2019. Resistant strains were characterized and typed by SpeI-PFGE. We have determined also AmpC production, we have performed DNA extraction and PCR exam. NGS with an Illumina Miseq platform was performed on representative strains to identify the mechanisms of C/T resistance.
Results: Over 34 pt, who have received C/T as therapy against multidrug resistant gram negative infections, 53% had CCI >3, 21% underwent to surgery in the previous three months, 32% had pneumonia as acute comorbidities, 18%has died, 26% have experienced a therapeutic failure. CCI>3, pneumonia, P.aeruginosa infection and a previous corticosteroid therapy were a negative prognostic factors. P.aeruginosa resulted resistant to carbapenem, cephalosporin, piperacillina/tazobactam and fluorochinolons, but not to colistin. Over 317 isolated and screened isolates, 15 were resistant to C/T (MIC > 8 mg/L; 4.73%). PFGE showed that 8/15 were strictly related. NGS revealed 6 different STs. The resistance mechanisms to C/T included the metallo β-lactamase (MBL)-econding genes blaVIM-2 in 8 isolates belonging to ST111, and blaIMP in 2 isolates (blaIMP-19 in ST175 and blaIMP-13 in ST621). Additionally, blaPER-1 β-lactamase gene was detected in 2 isolates (ST235) and the blaGES β-lactamase gene in 1 isolate (ST175). Notably, in 2 strains (ST70 and ST3354) no acquired β-lactamase genes involved in C/T resistance has been detected but they showed alterations in ampC. Modifications in these genes and in ampC promoter (ampR) were also detected in all resistant strains except in ST175 isolates (possessing a wild type ampC and ampR).
Conclusions: C/T has confirmed its high activity and efficacy against multidrug gram negative infections. There was a low rate of resistance to C/T, but several resistance mechanisms were identified, among which production of MBLs was the most common. Moreover, we found a possible mini-outbreak of blaVIM positive strains. Despite what has been pointed out, we must recognize that this study is limited by the low number of enrolled patients, by the retrospectivity and by being monocentric, but it can be considered an initial approach for further prospective future studies, involving other hospitals in the Region, to better to define both the therapeutic efficacy of C / T and the epidemiology of P. aeruginos
Direct acting antivirals (DAAs) for the treatment of HCV infection in HIV/HCV coinfected patients: a clinical experience.
No full textBackground
HIV/hepatitis C virus (HCV) coinfection has an unfavourable influence on the natural history of HCV, resulting in an increased rate of progression to cirrhosis, HCC and end stage liver disease. Although direct acting antivirals (DAAs) have proven to be effective in eradicating HCV infection in coinfected individuals, few data on cost effectiveness in clinical practice are available to date.
Purpose
This prospective study aims to assess efficacy and costs of DAAs in an outpatient population of HIV/HCV coinfected subjects.
Material and methods
A database for DAA prescription monitoring was created, including information on the overall cost of the anti-‐HCV regimen for each patient. Patients were treated according to the local prescription regulations. Virologic response to DAAs was assessed at weeks 4, 12 and 24 after treatment initiation. Additional clinical and laboratory data were obtained from the medical records.
Results
35 subjects were studied (males 80%, mean age 51 years), 23 undergoing a 12 week treatment course and 12 a 24 week course. Prior to initiation, 74% of patients had HIV plasma viral load below the detection limit. 80% changed at least one HIV medication to minimise the risk of drug-‐drug interactions; eventually, 71% switched to an integrase inhibitor based regimen. 87% of patients undergoing a 12 week DAA regimen had HCV genotype 1 infection whereas 67% of patients on a 24 week regimen had genotype 3. An interferon free regimen was chosen for 91% of patients. Ribavirin was used in combination with DAAs in 57% of subjects. Preferred combinations were simeprevir/sofosbuvir for the treatment of genotype 1 and sofosbuvir/ribavirin or daclatasvir/sofosbuvir for genotype 3. Other combinations were paritaprevir/dasabuvir/ombitasvir/ritonavir and ledipasvir/sofosbuvir. 55% of patients showed undetectable HCV viraemia at week 4 and 86% at week 12. To date, 22 patients have completed the full treatment course (19 patients 12 weeks, 3 patients 24 weeks), all showing undetectable HCV viraemia. Among these, 23% experienced mild side effects, all related to ribavirin co-administration (anaemia, fatigue). Mean treatment cost was approximately 55,000€ per patient.
Conclusion
This prospective study shows the effectiveness and safety of DAA therapy in HIV/HCV coinfected individuals in the clinical setting, despite the high cost. Data collection on sustained virologic response after treatment discontinuation is still ongoing
Efficacy and costs of Direct Acting Antivirals (DAAS) for the treatment of HCV Iinfection amnog HCV-monoinfected and HIV/HCV co-infected patients in real-life setting
No full textBACKGROUND
Although several studies analyzing the effectiveness of DAAs have showed no differences between HCV-monoinfected and HIV/HCV-coinfected patients,data in real-life setting are still limited.
PURPOSE
To compare efficacy and costs of DAAs in HCV-monoinfected and HIV/HCV-coinfected subjects.
METHODS
A database of HCV-monoinfected and HIV/HCV-coinfected adults who started HCV therapy between January 2015 and July 2016 was created in order to collect the following data:sustained virological response to DAAs therapy at week 12(SVR12) and at week 24(SVR24) after treatment initiation, treatment regimen, and overall cost of anti-HCV regimens.Patients were treated as follows: sofosbuvir/ribavirin ± peg-INF (n=37), sofosbuvir/daclatasvir(n=72), sofosburiv/ledipasvir(n=68), sofosburiv/simeprevir(n=77), simeprevir/peg-interferon(n=13) or ombitasvir/paritaprevir/ritonavir/dasabuvir(n=14). Overall, ribavirin was used in combination with DAAs in 67% of patients.
RESULTS
The study enrolled 281 subjects(81% monoinfected and 19% co-infected), treated for 12(54% of monoinfected and 50% of co-infected) or 24 weeks(46% of monoinfected and 50% of co-infected). Two hundred and twenty nine patients had cirrhosis or high degree fibrosis (≥F3) at the beginning of DAAs (79% of HCV-monoinfected and 91% of HIV/HCV co-infected);other 23 subjects(all but one HCV-monoinfected) were treated after liver transplantation. Two hundreds and ten (93%) HCV-monoinfected patients completed the treatment; 96% achieved SVR12 and 97% reached SVR24. The most prescribed regimens were 12-week sofosburiv/simeprevir(27%) or sofosburiv/ledipasvir(17%), and 24-week sofosbuvir/daclatasvir(17%). The average cost of a complete HCV-treatment in monoinfected population was € 49.633 per patient. Among the 47 HIV/HCV-coinfected patients(87%) who completed the treatment, 94% achieved SVR12 and 96% obtained SVR24;12-week sofosburiv/simeprevir was prescribed to 24% of them, whereas the most frequent 24-week treatments were sofosburiv/daclatasvir and sofosburiv/ledipasvir(20% each). The average cost of a complete HCV-treatment in coinfected population was € 53.573 per patient.
CONCLUSION
This study confirms the high effectiveness of DAAs in the treatment of HCV infection in real life setting, both in HCV-monoinfected and HIV/HCV-coinfected patients. The average cost of single treatment was also similar between the two groups
Antiretroviral therapy management and rationalisation of available resources
Full text linkThe treatment of HIV disease has led to a new division of management costs by shifting most of the necessary resources from inpatient treatment to outpatient management. Among the initiatives aimed at rationalising the resources available, we compared efficacy, tolerability and pharmacoeconomic impact of different regimes of antiretroviral therapy (ART). The survey covered the first 50 patients, clinically stable and with good viro-immunological response, who switched in June 2012 from an ART based on the triple combination of tenofovir (TDF), emtricitabine (FTC) and a protease inhibitor boosted with ritonavir (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI), to a treatment based on abacavir (ABC), lamivudine (3TC) and a PI/r or NNRTI. Of the 50 patients who operated the switch, 39 replaced a PI with nevirapine (NVP), for which the largest group of patients was treated with ABC + 3TC + NVP. On 31 May 2015, all patients completed the observation period of 96 weeks, with a mean observation period of 132 weeks and clinical-laboratory checks every four months. Laboratory analysis revealed an optimal maintenance of viral suppression and absolute and relative number of CD4 + lymphocytes and improving trend of creatinine, proteinuria, serum phosphate and bone alkaline phosphatase. There was a variable effect on lipids, with a drop in triglycerides associated with a modest increase in total cholesterol. Much of the HIV-positive population reporting to our hospitals (>50%) comprises individuals who have for years been in stable viraemic suppression, making a satisfactory immune recovery while in good overall clinical condition. This type of patient was the target of the present survey. At the end of 96 weeks of observation the new regimes were well tolerated and did not lead to viro-immunological or clinical deterioration. Pharmacoeconomic analysis showed better containment of the overall costs. No patient needed to be hospitalised during the observation period
Antiretroviral therapy management and rationalisation of available resources
No full textThe treatment of HIV disease has led to a new division of management costs by shifting most of the necessary resources from inpatient treatment to outpatient management. Among the initiatives aimed at rationalising the resources available, we compared efficacy, tolerability and pharmacoeconomic impact of different regimes of antiretroviral therapy (ART). The survey covered the first 50 patients, clinically stable and with good viro-immunological response, who switched in June 2012 from an ART based on the triple combination of tenofovir (TDF), emtricitabine (FTC) and a protease inhibitor boosted with ritonavir (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI), to a treatment based on abacavir (ABC), lamivudine (3TC) and a PI/r or NNRTI. Of the 50 patients who operated the switch, 39 replaced a PI with nevirapine (NVP), for which the largest group of patients was treated with ABC + 3TC + NVP. On 31 May 2015, all patients completed the observation period of 96 weeks, with a mean observation period of 132 weeks and clinical-laboratory checks every four months. Laboratory analysis revealed an optimal maintenance of viral suppression and absolute and relative number of CD4 + lymphocytes and improving trend of creatinine, proteinuria, serum phosphate and bone alkaline phosphatase. There was a variable effect on lipids, with a drop in triglycerides associated with a modest increase in total cholesterol. Much of the HIV-positive population reporting to our hospitals (>50%) comprises individuals who have for years been in stable viraemic suppression, making a satisfactory immune recovery while in good overall clinical condition. This type of patient was the target of the present survey. At the end of 96 weeks of observation the new regimes were well tolerated and did not lead to viro-immunological or clinical deterioration. Pharmacoeconomic analysis showed better containment of the overall costs. No patient needed to be hospitalised during the observation period
Spread of colistin resistance gene mcr-1 in Italy: characterization of the mcr-1.2 allelic variant in a colistin-resistant blood isolate of Escherichia coli
No full textmcr-1.2, an allelic variant of the transferable colistin resistance gene mcr-1, was characterized in a colistin-resistant blood isolate of Escherichia coli. It was harbored by an IncX4-type plasmid (33,293 bp). Despite its low prevalence, the potentially worrying spread of the mcr-1 gene, particularly its mcr-1.2 variant, in Italy requires increasing surveillance
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
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
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