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To promote judicious prescribing of methicillin-resistant Staphylococcus aureus (MRSA)-active therapy for skin and soft tissue infections (SSTI), we previously developed an MRSA risk assessment tool. The objective of this study was to validate this risk assessment tool internationally.A multicenter, prospective cohort study of adults with purulent SSTI was performed at seven international sites from July 2016 to March 2018. Patient MRSA risk scores were computed as follows: MRSA infection/colonization history (2 points); previous hospitalization, previous antibiotics, chronic kidney disease, intravenous drug use, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), diabetes with obesity (1 point each). Predictive performance of MRSA surveillance percentage, MRSA risk score, and estimated MRSA probability (surveillance percentage adjusted by risk score) were quantified using the area under the receiver operating characteristic curves (aROC) and compared. Performance characteristics of different risk score thresholds across varying baseline MRSA prevalence were examined.Two hundred three patients were included. Common SSTI were wounds (28.6%), abscess (25.1%), and cellulitis with abscess (20.7%). Patients with higher risk scores were more likely to have MRSA (P 0.001). The MRSA risk score aROC (95%CI) [0.748 (0.678-0.819)] was significantly greater than MRSA surveillance percentage [0.646 (0.569-0.722)] (P = 0.016). Estimated MRSA probability aROC [0.781 (0.716-0.845)] was significantly greater than surveillance percentage (P 0.001) but not the risk score (P = 0.192). The estimated negative predictive value (NPV) of an MRSA score ≥ 1 (i.e., a score of 0) was greater than 90% when MRSA prevalence was 30% or less.The MRSA risk score and estimated MRSA probability were significantly more predictive of MRSA compared with surveillance percentage. An MRSA risk score of zero had high predictive value and could help avoid unnecessary empiric MRSA coverage in low-acuity patients. Further study, including impact of such risk assessment tools on prescribing patterns and outcomes are required before implementation.

Background Candida species are among the most frequent causative agents of health care–associated bloodstream infections, with mortality >40% in critically ill patients. Specific populations of critically ill patients may present peculiar risk factors related to their reason for intensive care unit admission. The primary objective of the present study was to assess the predictors of candidemia after open heart surgery. Methods This retrospective, matched case–control study was conducted in 8 Italian hospitals from 2009 to 2016. The primary study objective was to assess factors associated with the development of candidemia after open heart surgery. Results Overall, 222 patients (74 cases and 148 controls) were included in the study. Candidemia developed at a median time (interquartile range) of 23 (14–36) days after surgery. In multivariable analysis, independent predictors of candidemia were New York Heart Association class III or IV (odds ratio [OR], 23.81; 95% CI, 5.73–98.95; P Conclusions Previous broad-spectrum antibiotic therapy and high NYHA class were independent predictors of candidemia in cardiac surgery patients with prolonged postoperative intensive care unit stay.

The authors present the case of a critically ill morbidly obese patient (body mass index, 51.2 kg/m) who suffered from methicillin-resistant Staphylococcus epidermidis, and Candida albicans bloodstream infections. Initial treatment with caspofungin and daptomycin was deemed inappropriate, because blood cultures remained positive for both isolates after 14 days. The clinical pharmacological consultant suggested adding fluconazole and ceftobiprole to the ongoing antimicrobial therapy, and starting a real-time therapeutic drug monitoring program of daptomycin, ceftobiprole, and fluconazole, aimed at optimizing plasma exposures. Punctual minimum inhibitory concentration knowledge on the clinical isolates allowed attainment of the desired pharmacodynamic efficacy targets. Within few days, the patient greatly improved, as blood cultures became negative, and the inflammatory markers decreased to near normal values. This is a proof-of-concept of the importance of a therapeutic drug monitoring-based multidisciplinary approach in the proper management of complex antimicrobial therapy in special populations.

To assess the added value of serial 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake analysis in predicting clinical response to treatment in infectious spondylodiscitis (IS). We sought to analyze changes in quantitative FDG-PET/CT parameters among patients with clinical response or treatment failure and to compare the sensitivity and specificity of serial FDG-PET/CT and MRI in predicting treatment response in IS. This retrospective study consisted of 68 FDG-PET/CT examinations in 34 patients performed before and after at least 2 weeks of antibiotic treatment. Serial MRI scans were available in 32 (94%) patients before and after treatment. FDG-avid lesions were quantified as maximum standardized uptake value (SUVmax), partial-volume corrected lesion metabolic volume (LMV), and partial-volume corrected lesion metabolic activity (LMA). All FDG-PET/CT parameters significantly decreased in patients with clinical improvement (31/34, 91%, P 15% and > 25% showed 94% and 89% sensitivity and 67% and 100% specificity compared with 37% and 50% of MRI, respectively. Low degree of agreement with clinical response was shown for MRI compared with FDG-PET/CT parameters using the Cohen kappa coefficient. FDG-PET/CT monitoring is a valuable tool to predict clinical response to treatment in IS and has greater sensitivity and specificity compared with MRI.

Isavuconazole is a newer broad-spectrum triazole approved for the treatment of invasive fungal disease. The objective of this study was to conduct a population pharmacokinetic and pharmacodynamic analysis of isavuconazole in a retrospective cohort of hospitalized patients. A nonlinear mixed-effect approach with Monte Carlo simulations was conducted to assess the probability of target attainment (PTA) of an area under the concentration–time curve (AUC24 h)/minimum inhibitory concentration (MIC) ratio of 33.4 (defined as efficacy threshold against A. fumigatus and A. flavus) associated with a maintenance dose (MD) of 100, 200 and 300 mg daily after loading. The cumulative fraction of response (CFR) against the EUCAST MIC distributions of A. fumigatus and A. flavus was calculated as well. The proportion of trough concentrations (Ctrough) exceeding a defined threshold of toxicity (>5.13 mg/L) was estimated. A total of 50 patients, with a median age of 61.5 years, provided 199 plasma isavuconazole concentrations. Invasive pulmonary aspergillosis was the prevalent type of infection and accounted for 80% (40/50) of cases. No clinical covariates were retained by the model. With the standard MD of 200 mg daily, CFRs were always ≥90% during the first two months of treatment. The risk of Ctrough < 1.0 mg/L was around 1%, and that of Ctrough > 5.13 mg/L was 27.7 and 39.2% at 28 and 60 days, respectively, due to isavuconazole accumulation over time. Our findings suggest that TDM for isavuconazole should not be considered as mandatory as for the other mold-active azoles voriconazole and posaconazole.

O estande de plantas é um fator muito relevante para a produtividade da cultura do algodoeiro. O experimento foi instalado na Fazenda Divisão em Lucas do Rio Verde, MT, utilizando a cultivar TMG 41 WideStrike, WS (resistente a lagartas). O delineamento experimental inteiramente ao acaso com 6 tratamentos e 3 repetições. Para reduzir os custos com a lavoura de algodão, reduzir a quantidade de sementes seria interessante, então esse trabalho ensaiou as seguintes populações: 6; 8; 10;11;12 e 15 sementes por metro linear (66.666; 88.888; 111.111; 122.222; 133.333; 166.666 plantas por hectares), com espaçamento entre linhas de 90 cm. Os tratos culturais foram os mesmos para todas as parcelas. A altura da planta e diâmetro do caule também foram observada e a diferença foi significativa perante as desiguais populações de planta. Quanto maior a densidade, maior foi a altura e menor foi a largura do caule. Os resultados de produtividade foram diferentes, mas pela análise de variância, a produtividade não foi afetada pela população de plantas, sendo assim, com as menores populações, 66.666 e 88.888 pl.ha-1, a produtividade é semelhante e o custo é menor.

Contains fulltext : 206779.pdf (Publisher’s version ) (Open Access) BACKGROUND: The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. METHODS: A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). RESULTS: During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis. CONCLUSIONS: The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.

Introduction Fungal infections are a significant and increasing public health problem worldwide, that range in severity from mild superficial infections that affect a large proportion of the otherwise healthy population to life-threatening invasive diseases limited mostly to vulnerable immunosuppressed patients (1). Patients that are at risk for fungal infections, those hospitalised with serious underlying diseases, such as those with HIV infection, haemato-oncological malignancies, recipients of immunosuppressive therapies, solid-organ or hematopoietic stem cell transplant (HSCT) recipients (2). The incidence of fungaemia is growing and has dramatically increased within the past two decades. Such infections have been attributed to the common practice of prolonged hospitalisation of highly susceptible patients receiving advanced medical treatment; such conditions render patients more susceptible to invasive fungal infections (3,4)The populations of patients at risk have expanded to include those with usually multiple underlying medical conditions, such as diabetes mellitus, chronic obstructive pulmonary diseases and those receiving corticosteroids (3,4) The current number of fungal infections occurring each year in Italy is not known. The aim of this work was to estimate the burden of fungal infections in Italy, a country, with a population of 61 millions. As invasive fungal infections are not reportable, exact data are not available. For this reason, we have taken different approaches to explore the current number of invasive fungal infections. First, we have estimated fungal infections based on populations at risk, with data from published Italian or international cohort studies and clinical trials.Material and methodsThe burden of serious fungal infections was estimated for general healthy population and for specific at-risk groups, including patients affected by HIV infection, respiratory diseases (COPD, asthma and tuberculosis), solid organ or hematologic malignancy and critical illness.Demographic data regarding Italian population were obtained from the Italian National Statistical Institute (ISTAT) (5).Data on the HIV/AIDS population were obtained from the Epicentro-National Institute of Health (Istituto Superiore di Sanità-ISS) (6) and recent published data estimating adult HIV prevalence in Italy (7).Tuberculosis statistics were taken from the Epicentro-National Institute of Health (ISS) (6) and World Health Organization (WHO) reports (8). COPD and asthma prevalence in Italy were obtained from the Health Examination Survey (OEC/HES) 2008-2012(9).Solid organ cancer and haematological diseases cases were taken from Associazione Italiana Oncologia Medica (AIOM) (10) and Associazione Italiana dei Registri Tumori (AIRTUM) reports (11).Country’s profile, populations and rates required to calculate burden of serious fungal infections are reported in Table 1.We conducted an extensive literature review and published epidemiology papers reporting fungal infections incidence and/or prevalence in Italy were identified.Where no national data existed, authors reviewed data from published single-center or multicentre trials and from public health institutions in Italy. Moreover, in selected cases, when Italian data were not available, we calculated Italian fungal burden based on fungal infection incidence in other European countries. RESULTSCountry profile Italy is a country with an estimated population of 61 million people, represented by adults ( 14 years) in up to 85% of cases. Of the general population, approximately 13 million (22%) are older than 65 years. Chronic obstructive pulmonary disease prevalence has been estimated in 3.5-5% in men and 2.3 - 3.3% in women overall among adult population, with the large majority of patients in classified as GOLD stage I. The number of HIV-infected patients ranged between 114.000 and 156.000 people, with approximately 84% of patients receiving ARV (7). Solid organ cancer prevalence is 3.037.127 cases, accounting for approximately 5% of overall population (11). The exact prevalence of patients with hematological malignancies is not available, but an estimated number of 31.300 new diagnosis per year, mainly represented by non-Hodgkin lymphoma and acute leukemia has been reported in Italian registries (11). The number of autologous and allogeneic HSCTs is available at the registry of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) and accounted in 2016 for 2905 and 1796 transplants, respectively (www.gitmo.it). Country’s profile, populations and rates required to calculate burden of serious fungal infections are reported in Table 1. Prevalence rates previously reported used to estimate the burden of serious fungal infections are reported in Table 2.

Introduction Tedizolid phosphate is an oxazolidinone approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) and active against methicillin-resistant Staphylococcus aureus. Aims The objective of this article was to review the evidence for the efficacy and safety of tedizolid phosphate for the treatment of ABSSSI. Evidence review Approval of tedizolid phosphate for the treatment of ABSSSI was based on the results of two phase III randomized controlled trials, ESTABLISH-1 (NCT01170221) and ESTABLISH-2 (NCT01421511), comparing 6-day once-daily tedizolid vs 10-day twice-daily linezolid. In ESTABLISH-1, noninferiority was met with early clinical response rates of 79.5% and 79.4% in tedizolid and linezolid groups, respectively (difference 0.1%, 95% CI -6.1% to 6.2%, with a 10% noninferiority margin). In ESTABLISH-2, noninferiority was met with 85% and 83% rates of early clinical response in tedizolid and linezolid groups, respectively (difference 2.6%, 95% CI -3.0% to 8.2%). Pooled data from ESTABLISH-1 and ESTABLISH-2 indicated a lower frequency of thrombocytopenia in tedizolid-treated than in linezolid-treated patients. Conclusion Tedizolid offers the option of an intravenous to oral switch, allows once-daily administration, and presents lower risk of myelotoxicity when a 6-day course is used for the treatment of ABSSSI. Greater economic cost associated with this antibiotic could be offset by its shorter treatment duration and possibility of oral administration in routine clinical practice, although either sponsored or nonsponsored postmarketing observational experience remains essential for ultimately confirming the effectiveness and tolerability of tedizolid outside clinical trials.

Purpose of review An increase of skin and soft tissue infections involving Staphylococcus aureus has been reported in community and hospital settings. Methicillin resistance in S. aureus is associated with treatment failure and increased mortality. Recently, new antimicrobials with enhanced activity against methicillin-resistant Staph. aureus have been approved for the treatment of skin and soft tissue infections. Among these, novel oxazolidinones and lipoglycopeptides represent options with favorable pharmacokinetic characteristics and safety profiles. Recent findings Newly approved compounds include tedizolid, characterized by the availability of both oral and intravenous formulation and once daily administration and dalbavancin, a long-acting antimicrobial allowing for weekly administration. These new molecules present advantages, such as enhanced activity against multidrug-resistant Gram-positive bacteria and favorable safety profiles. Summary We have reviewed the pharmacokinetic characteristics and the implications for use in skin and soft tissue infections of tedizolid and dalbavancin. Advantages associated with the use of these compounds include the possibility for early patient discharge, reduced hospital length of stay, and outpatient treatment, with potential impact on morbidity, mortality, and overall health-care costs.

Background Fluconazole represents a common antifungal option for the treatment of Candida infections in liver transplant recipients. Although adequate antifungal exposure is known to correlate with favorable outcomes in patients with invasive candidiasis, therapeutic drug monitoring (TDM) of fluconazole is currently not recommended. Methods We conducted a retrospective study including adult liver transplant recipients receiving fluconazole for invasive candidiasis and undergoing TDM. We assessed the correlation between clinical variables, fluconazole trough plasma levels (Cmin ), and outcome. Results Twenty-seven patients (74% males; median age 57 years) were included. Abdominal candidiasis was the most frequent infection (56%). Median duration of fluconazole therapy was 17 days (IQR 9-21). Fluconazole median Cmin was 11.0 mg/L (range 2.4-30.6 mg/L). Five (19%) patients required TDM-guided fluconazole dose increase. All-cause in hospital mortality was 33%. Fluconazole Cmin >11 mg/L significantly correlated with clinical success (OR 8.78, 95% CI 1.13-67.8, P = 0.04). Conclusions Our study identified decreased fluconazole Cmin as a factor associated with negative outcomes in liver transplant recipients with Candida infection. TDM of fluconazole may be advisable in this patient population.

Proponer hacer. Sí, pero ¿cómo? se presentan criterios para el trabajo con actividades y consignas en las propuestas didácticas. Es un material que se dirige principalmente a quienes se desempeñan en la escuela secundaria, aunque, seguramente, quienes se encuentran en otros niveles educativos también podrán encontrar aquí, cuestiones valiosas para recuperar y reflexionar sobre sus prácticas en lo que respecta a esa parte vital de la enseñanza. https://www.uepc.org.ar/conectate/subserie-apuntes-docentes-proponer-hacer-si-pero-como/ Fil: Carnelutti, Jenifer. Unión de Educadores de la Provincia de Córdoba. Instituto de Capacitación e Investigación de los Educadores de Córdoba; Argentina. Fil: Zamanillo, Agustina. Unión de Educadores de la Provincia de Córdoba. Instituto de Capacitación e Investigación de los Educadores de Córdoba; Argentina. Fil: Moreiras, Diego Agustín. Unión de Educadores de la Provincia de Córdoba. Instituto de Capacitación e Investigación de los Educadores de Córdoba; Argentina. Fil: Moreiras, Diego Agustín. Universidad Nacional de Córdoba. Facultad de Ciencias de la Comunicación. Cátedra de Taller de Práctica Docente III; Argentina. Educación general (incluye capacitación, pedagogía y didáctica)

Objectives To analyze risk factors for early and late mortality in individuals aged 75 and older with Staphylococcus aureus bacteremia (SAB) in Italy. Design Four‐year retrospective observational study (January 2011‐December 2014). Setting Two tertiary care university hospitals in Italy (Santa Maria Misericordia Hospital in Udine, Policlinico Universitario Agostino Gemelli in Rome). Participants All adults consecutively admitted with SAB. Measurements Clinical presentation, infection characteristics, and clinical outcomes of individuals aged 75 and older were compared with those of individuals younger than 75. Results Three hundred thirty‐seven cases of SAB were diagnosed during the study period, 118 of which (35%) occurred in those aged 75 and older. Seven‐ (20.3% vs 9.2%) and 30‐day (35.7% vs 20.7%) mortality were significantly higher in elderly than younger adults. Clinical presentation with septic shock, adequacy of empiric antibiotic treatment, and liver cirrhosis were found to be predictors of 7‐day mortality in elderly adults with SAB. Risk factors independently associated with 30‐day mortality included isolation of methicillin‐resistant Staphylococcus aureus (MRSA) and not receiving an infectious disease consultation. Conclusion Mortality is significantly higher in elderly than in younger adults with SAB, particularly in those presenting with septic shock, liver cirrhosis, or SAB due to MRSA. Additional risk factors for mortality included inappropriate empiric antibiotic treatment and not receiving an infectious disease consultation.

The increase of skin and soft tissue infections (SSTIs) represents a major concern both in community and in the hospital setting. Staphylococcus aureus is the most frequently isolated pathogen, and the rise in infections due to methicillin-resistant Staphylococcus aureus (MRSA) has been associated with inadequate antibiotic treatment and increased morbidity.A number of new antimicrobials with activity against drug-resistant Gram-positive pathogens, including MRSA, have been recently approved for the treatment of SSTIs. New lipoglycopeptides, in particular dalbavancin, are long-acting antibiotics with potential for infrequent administration, offering the possibility for outpatient treatment and early hospital discharge.Dalbavancin is a new lipoglycopeptide showing high activity against Gram-positive bacteria, including drug-resistant strains. Dalbavancin presents a distinctive pharmacokinetic profile with a terminal prolonged half-life of approximately 14 days. This characteristic allows once-weekly dosing interval, avoiding the need for daily dosing and offering an advantage over other compounds for potential use in the outpatient setting or to promote early hospital discharge. Dalbavancin has a favorable adverse effect profile and appears to be a promising new alternative for treatment of SSTIs. We have reviewed the pharmacokinetic properties of dalbavancin and the clinical evidence for its use in complicated SSTIs and other potential applications.

Candida endocarditis represents a life-threatening infection with high mortality rates despite adequate antifungal treatment. Step-down oral treatment with fluconazole or voriconazole represents a treatment option for clinically stable patients. Drug toxicity, however, is reported during azole therapy and can be challenging, especially among patients with multiple comorbidities. This is the first report that highlights the impact of isavuconazole on the corrected QT interval and liver toxicity in a cirrhotic patient with Candida endocarditis.

Matteo Bassetti,1,2Nadia Castaldo,1 Alessia Carnelutti,1 Maddalena Peghin,1 Daniele Roberto Giacobbe21Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy; 2Department of Health Sciences, University of Genoa, Genoa, ItalyIntroduction: Tedizolid phosphate is an oxazolidinone approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) and active against methicillin-resistant Staphylococcus aureus.Aims: The objective of this article was to review the evidence for the efficacy and safety of tedizolid phosphate for the treatment of ABSSSI.Evidence review: Approval of tedizolid phosphate for the treatment of ABSSSI was based on the results of two phase III randomized controlled trials, ESTABLISH-1 (NCT01170221) and ESTABLISH-2 (NCT01421511), comparing 6-day once-daily tedizolid vs 10-day twice-daily linezolid. In ESTABLISH-1, noninferiority was met with early clinical response rates of 79.5% and 79.4% in tedizolid and linezolid groups, respectively (difference 0.1%, 95% CI –6.1% to 6.2%, with a 10% noninferiority margin). In ESTABLISH-2, noninferiority was met with 85% and 83% rates of early clinical response in tedizolid and linezolid groups, respectively (difference 2.6%, 95% CI –3.0% to 8.2%). Pooled data from ESTABLISH-1 and ESTABLISH-2 indicated a lower frequency of thrombocytopenia in tedizolid-treated than in linezolid-treated patients.Conclusion: Tedizolid offers the option of an intravenous to oral switch, allows once-daily administration, and presents lower risk of myelotoxicity when a 6-day course is used for the treatment of ABSSSI. Greater economic cost associated with this antibiotic could be offset by its shorter treatment duration and possibility of oral administration in routine clinical practice, although either sponsored or nonsponsored postmarketing observational experience remains essential for ultimately confirming the effectiveness and tolerability of tedizolid outside clinical trials.Keywords: ABSSSI, MRSA, oxazolidinone, Staphylococcus, efficacy, safety