Resistance to echinocandins in pacients with persistent candidaemia

Candidemia persistente tem sido descrita como uma complicacao do quadro de candidemia, caracterizada pelo isolamento de Candida spp. em amostras sequenciais de hemocultura apos o diagnostico inicial, mesmo em pacientes expostos ao tratamento antifungico adequado. Embora fatores predisponentes relacionados ao hospedeiro ja estejam bem estabelecidos, poucos estudos tem analisado os atributos do patogeno envolvidos no desenvolvimento dessa complicacao. O objetivo do presente estudo foi avaliar a ocorrencia de resistencia as equinocandinas em isolados de Candida spp. provenientes de pacientes com candidemia persistente submetidos a terapia antifungica com esta classe de farmaco. As amostras foram identificadas atraves de sequenciamento da regiao ITS do rDNA. O perfil de susceptibilidade in vitro aos antifungicos foi realizado utilizando metodologia de microdiluicao em caldo (CLSI, documento M27-S4). Alem disso, nos avaliamos a ocorrencia de resistencia a partir do sequenciamento do gene FKS1. Dentre 436 pacientes com candidemia, 63 (14,4%) apresentaram quadros de candidemia persistente, desses, 13 atenderam aos criterios de inclusao estabelecidos no presente estudo. Atraves das identificacoes fenotipica e molecular, foi observado 5 dos 13 pacientes (38,5%) foram infectados por isolados de C. parapsilosis (sensu stricto), 3 (23%) por isolados de C. albicans, 2 (15,4%) por isolados de C. krusei, 1 (7,7%) por isolado de C. tropicalis e 1 (7,7%) teve como agente etiologico da candidemia isolados de C. orthopsilosis. Alem disso, um paciente (7,7%) apresentou episodio de infeccao mista com alternancia de isolamento de duas diferentes especies, C. tropicalis e C. parasilosis (sensu stricto). Em relacao ao perfil de susceptibilidade aos antifungicos, a grande maioria dos isolados foi classificada como sensivel a todos os antifungicos testados, com excecao dos cinco isolados de C. krusei provenientes dos pacientes 2 (dois isolados) e 10 (tres isolados), os quais apresentaram resistencia ao fluconazol e a caspofungina, sendo que dois deles foram intermediarios a anidulafungina. Nao foi verificado aumento de valores de CIM entre os isolados sequenciais de um mesmo paciente a despeito do tratamento antifungico utilizado. Nenhum dos isolados apresentou mutacao nas regioes dos HS1 e HS2 do gene FKS1, sendo classificados como selvagens em relacao aos genotipos de resistencia ja descritos. Por outro lado, os isolados de C. krusei apresentaram mutacao nao sinonima em regiao muito proxima ao HS1, o que poderia, ao menos em parte, explicar o desfecho clinico negativo durante tratamento com equinocandinas e os elevados valores de CIM observados para estes isolados. Os dados obtidos no presente estudo mostram que a ocorrencia de resistencia as equinocandinas ainda permanece rara em nosso meio, mesmo quando analisada em coorte de pacientes com risco elevado a ocorrencia de tal fenomeno. Por fim, conclui-se que as caracteristicas clinicas do paciente parecem ter maior relevancia que os mecanismos de resistencia as equinocandinas no que se refere a ocorrencia de candidemia persistenteBV UNIFESP: Teses e dissertaçõe

Analysis of time variability in Lean Healthcare: a case study in a Brazilian emergency room

Lean Healthcare has often been used as a strategy for operational improvement activities in hospitals. In this sense, this article aims to present a statistical approach applied in existing situations in hospital processes, more specifically, a first aid hospital in Brazil. The TSA (Time Statistical Approach) consists of the construction of confidence intervals for the mean, through the use of the Student t distribution. The results of this application were presented in a case study carried out at a first aid center. The results of the TSA application have shown that variability in activity and wait times can directly affect the improvement efforts involved. The case study also shows that obtaining the standardization of work in hospital environments may require much more effort than in manufacturing environments

Prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period

To describe temporal trends in the epidemiology, clinical management and outcome of candidemia in intensive care unit (ICU) patients.This study was a retrospective analysis of 1,392 episodes of candidemia in 647 adult ICU patients from 22 Brazilian hospitals. the characteristics of candidemia in these ICU patients were compared in two periods (2003-2007, period 1; 2008-2012, period 2), and the predictors of 30-day mortality were assessed.The proportion of patients who developed candidemia while in the ICU increased from 44 % in period 1 to 50.9 % in period 2 (p = 0.01). Prior exposure to fluconazole before candidemia (22.3 vs. 11.6 %, p < 0.001) and fungemia due to Candida glabrata (13.1 vs. 7.8 %, p = 0.03) were more frequent in period 2, as was the proportion of patients receiving an echinocandin as primary therapy (18.0 vs. 5.9 %, p < 0.001). the 30-day mortality rate decreased from 76.4 % in period 1 to 60.8 % in period 2 (p < 0.001). Predictors of 30-day mortality by multivariate analysis were older age, period 1, treatment with corticosteroids and higher APACHE II score, while treatment with an echinocandin were associated with a higher probability of survival.We found a clear change in the epidemiology and clinical management of candidemia in ICU patients over the 9-year period of the study. the use of echinocandins as primary therapy for candidemia appears to be associated with better outcomes.MSDPfizerUnited MedicalUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilHosp Serv Publ Estadual São Paulo, São Paulo, BrazilIrmandade Santa Casa de Misericordia Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Ciencias Sau Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Parana, BR-80060000 Curitiba, Parana, BrazilUniv Fed Rio de Janeiro, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilWeb of Scienc

Prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period (vol 40, pg 1489, 2014)

Universidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilHosp Serv Publ Estadual São Paulo, São Paulo, BrazilIrmandade Santa Casa de Misericordia Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Ciencias Saude Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Parana, BR-80060000 Curitiba, Parana, BrazilUniv Fed Rio de Janeiro, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilWeb of Scienc

Outbreak of candidemia caused by fluconazole resistant Candida parapsilosis strains in an intensive care unit

Background: Candidemia is an increasing problem in tertiary care hospitals worldwide. Here, we report the first outbreak of candidemia caused by fluconazole-resistant C. parapsilosis (FRCP) strains in Brazil. Methods: This was a cross-sectional study of clinical and microbiological data of all candidemic episodes diagnosed from July 2011 to February 2012 in a 200-bed tertiary care hospital. Initial yeast identification and susceptibility testing were performed using the VITEK 2 - System. Isolates of Candida spp. resistant to fluconazole were sent to a reference laboratory (LEMI-UNIFESP) for further molecular identification and confirmation of resistance by CLSI microdilution test. A multivariate analysis was conducted to identify factors associated with FRCP infection. Results: We identified a total of 40 critically ill patients with candidemia (15 women) with a median age of 70 years. The incidence of candidemia was 6 cases/1,000 patients admissions, including 28 cases (70 %) of infection with C. parapsilosis, 21 of which (75 %) were resistant to fluconazole. In only 19 % of FRCP candidemia cases had fluconazole been used previously. The results of our study indicated that diabetes is a risk factor for FRCP candidemia (p = 0.002). Overall, mortality from candidemia was 45 %, and mortality from episodes of FRCP infections was 42.9 %. Conclusions: The clustering of incident cases in the ICU and molecular typing of strains suggest horizontal transmission of FRCP. Accurate vigilant monitoring for new nosocomial strains of FRCP is required.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/04767-1]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil, (CNPq) [307510/2015-8]FAPESP [2012/04769-4]CNPqEd Amer Off Tower,SCN Q 1 BL F,Sala 1016, BR-70711905 Brasilia, DF, BrazilUniv Fed Sao Paulo, Rua Pedro de Toledo 669, BR-04039032 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Rua Pedro de Toledo 669, BR-04039032 Sao Paulo, SP, BrazilFAPESP:2012/04767-12012/04769-4CNPq:307510/2015-82012/04769-4Web of Scienc

D13.2 Techniques and performance analysis on energy- and bandwidth-efficient communications and networking

Deliverable D13.2 del projecte europeu NEWCOM#The report presents the status of the research work of the various Joint Research Activities (JRA) in WP1.3 and the results that were developed up to the second year of the project. For each activity there is a description, an illustration of the adherence to and relevance with the identified fundamental open issues, a short presentation of the main results, and a roadmap for the future joint research. In the Annex, for each JRA, the main technical details on specific scientific activities are described in detail.Peer ReviewedPostprint (published version

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

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication