Antimicrobial activity of daptomycin and selected comparators tested against bloodstream Staphylococcus aureus isolates from hemodialysis patients

Background: Patients on long-term hemodialysis are at a significantly higher risk for catheter-related bloodstream infections (BSI) than the general population. These infections are generally caused by Gram-positive organisms, especially Staphylococcus aureus. in the present study, we evaluated the antimicrobial susceptibility patterns of S. aureus causing BSI in dialysis patients compared to those causing BSI in other patient populations.Methods: the potencies of daptomycin and various comparator agents were evaluated by reference broth microdilution methods for S. aureus bloodstream isolates from dialysis patients (606 strains) in 43 hospitals in North America and Europe. Susceptibility patterns for the dialysis isolate set were compared to those S. aureus causing BSI in other patient populations in the same hospitals and time period.Results: Daptomycin was highly potent against S. aureus causing bacteremia in dialysis patients (MIC(50)/MIC(90), 0.25/0.5 mu g/ml). Vancomycin (MIC(50)/MIC(90), 1/1 mu g/ml) and linezolid (MIC(50)/MIC(90), 2/2 mu g/ml) showed similar potency, and overall susceptibility rates for the three antibiotics were 99.8-100.0% susceptible. Linezolid and vancomycin were four- to eight-fold less potent than daptomycin.Conclusions: the overall susceptibility patterns of S. aureus strains from dialysis patients were very similar to those of non-dialysis patients. (c) 2008 International Society for Infectious Diseases. Published by Elsevier B.V. All rights reserved.Cubist Pharmaceuticals, Inc.AB BIODISKAbbottAPIArpidaAstellasAstraZenecaAvexaBayerbioMerieuxCadenceCempraCerexaChironCornerstoneCubistDaiichiElanElancoEnantaGlaxoSmithKlineJohnson Et Johnson (Ortho McNeil)MerckNovartisOptimerOrdwayOsmoticsPacific BeachPeninsulaPfizerProtezReplidyneSchering-PloughSequoiaShionogiTheravanceTREK DiagnosticsViroPharmaWyethJMI Labs, N Liberty, IA 52317 USAUniversidade Federal de São Paulo, São Paulo, BrazilTufts Univ, Sch Med, Boston, MA 02111 USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Accuracy of three automated systems (MicroScan WalkAway, VITEK, and VITEK 2) for susceptibility testing of Pseudomonas aeruginosa against five broad-spectrum beta-lactam agents

One hundred recent clinical Pseudomonas aeruginosa isolates were used to assess the quantitative (MIC) and qualitative (susceptibility category) accuracies of the MicroScan WalkAway, VITEK, and VITEK 2 automated susceptibility test systems when five-broad spectrum beta-lactams, aztreonam, cefepime, ceftazidime, imipenem, and piperacillin-tazobactam, were tested. Isolates were selected so that the MICs for the isolates over-represented the MICs near the breakpoints to assess precisely the agreement between the results obtained with the automated systems and the results obtained by the reference tests. the categorical and MIC results from the automated systems were compared to the consensus result of three reference methods: broth microdilution, agar dilution, and disk diffusion. the consensus categorical testing (susceptibility and resistance) rates were 47 and 27%, respectively, for aztreonam; 59 and 14%, respectively, for cefepime; 44 and 43%, respectively, for ceftazidime; 71 and 19%, respectively, for imipenem; and 50 and 50%, respectively, for piperacillin-tazobactam. All systems tested exhibited a high, unacceptable level of very major (false-susceptible) errors for piperacillin-tazobactam (19 to 27%). Major (false-resistant) error rates were generally acceptable (0 to 3%), but minor error rates were elevated (8 to 32%) for cefepime (VITEK 2 and VITEK) and for aztreonam (all three systems), leading to consistent trends toward false resistance. Manufacturer reevaluation of these automated systems for the testing of selected beta-lactams with current clinical isolates of P. aeruginosa that exhibit contemporary resistance mechanisms would be prudent to minimize the potential for serious reporting errors.JMI Labs Inc, N Liberty, IA 52317 USAUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilTufts Univ, Sch Med, Boston, MA 02111 USAUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilWeb of Scienc

Potency and Bactericidal Activity of Iclaprim against Recent Clinical Gram-Positive Isolates

The in vitro activity of iclaprim, a novel diaminopyrimidine derivative, was evaluated against 5,937 recent gram-positive clinical isolates collected in the United States and Europe. Iclaprim demonstrated potent activity against Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA]), beta-hemolytic Streptococcus spp., and Enterococcus faecalis strains tested. in addition, iclaprim exhibited bactericidal activity against all S. aureus strains tested, including MRSA.Arpida AG (Reinach, Switzerland)JMI Labs, Beaver Kreek Ctr 345, N Liberty, IA 52317 USAUniversidade Federal de São Paulo, São Paulo, BrazilTufts Univ, Sch Med, Boston, MA 02111 USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Normalized indices derived from visceral adipose mass assessed by MRI and their correlation with markers for insulin resistance and prediabetes

Visceral adipose tissue (VAT) plays an important role in the pathogenesis of insulin resistance (IR), prediabetes and type 2 diabetes. However, VAT volume alone might not be the best marker for insulin resistance and prediabetes or diabetes, as a given VAT volume may differently impact on these metabolic traits based on body height, gender, age and ethnicity. In a cohort of 1295 subjects from the Tübingen Diabetes Family Study (TDFS) and in 9978 subjects from the UK Biobank (UKBB), undergoing magnetic resonance imaging for quantification of VAT volume, total adipose tissue (TAT, in the TDFS), total abdominal adipose tissue (TAAT) in the UKBB, and total lean tissue (TLT), VAT volume and several VAT-indices were investigated for their relationships with insulin resistance and glycemic traits. VAT-related indices were calculated by correcting for body height (VAT/m: VAT/body height; VAT/m²: VAT/(body height)², and VAT/m³: VAT/(body height)³), TAT (%VAT), TLT (VAT/TLT) and weight (VAT/WEI), with closest equivalents used within the UKBB dataset. Prognostic values of VAT and VAT-related indices for insulin sensitivity, HbA1c levels and prediabetes/diabetes were analyzed for males and females. Males had higher VAT volume and VAT-related indices than females in both cohorts (p < 0.0001) and VAT volume has shown to be a stronger determinant for insulin sensitivity than anthropometric variables. Among the parameters uncorrected VAT and derived indices, VAT/m³ most strongly correlated negatively with insulin sensitivity and positively with HbA1c levels and prediabetes/diabetes in the TDFS (R² = 0.375/0.305 for females/males for insulin sensitivity, 0.178/0.148 for HbA1c levels vs. – e.g. – 0.355/0.293 and 0.144/0.133 for VAT, respectively) and positively with HbA1c (R² = 0.046/0.042) in the UKBB for females and males. Furthermore, VAT/m³ was found to be a significantly better determinant of insulin resistance or prediabetes than uncorrected VAT volume (p < 0.001/0.019 for females/males regarding insulin sensitivity, p < 0.001/< 0.001 for females/males regarding HbA1c). Evaluation of several indices derived from VAT volume identified VAT/m³ to most strongly correlate with insulin sensitivity and glucose metabolism. Thus, VAT/m³ appears to provide better indications of metabolic characteristics (insulin sensitivity and pre-diabetes/diabetes) than VAT volume alone

New Frontiers in Food Production Beyond LEO

New technologies will be needed as mankind moves towards exploration of cislunar space, the Moon and Mars. Although many advances in our understanding of the effects of spaceflight on plant growth have been achieved in the last 40 years, spaceflight plant growth systems have been primarily designed to support space biology studies. Recently, the need for a sustainable and robust food system for future missions beyond Low Earth Orbit (LEO) has identified gaps in current technologies for food production. The goal is to develop safe and sustainable food production systems with reduced resupply mass and crew time compared to current systems

Evidence-based practice educational intervention studies: A systematic review of what is taught and how it is measured

Abstract Background Despite the established interest in evidence-based practice (EBP) as a core competence for clinicians, evidence for how best to teach and evaluate EBP remains weak. We sought to systematically assess coverage of the five EBP steps, review the outcome domains measured, and assess the properties of the instruments used in studies evaluating EBP educational interventions. Methods We conducted a systematic review of controlled studies (i.e. studies with a separate control group) which had investigated the effect of EBP educational interventions. We used citation analysis technique and tracked the forward and backward citations of the index articles (i.e. the systematic reviews and primary studies included in an overview of the effect of EBP teaching) using Web of Science until May 2017. We extracted information on intervention content (grouped into the five EBP steps), and the outcome domains assessed. We also searched the literature for published reliability and validity data of the EBP instruments used. Results Of 1831 records identified, 302 full-text articles were screened, and 85 included. Of these, 46 (54%) studies were randomised trials, 51 (60%) included postgraduate level participants, and 63 (75%) taught medical professionals. EBP Step 3 (critical appraisal) was the most frequently taught step (63 studies; 74%). Only 10 (12%) of the studies taught content which addressed all five EBP steps. Of the 85 studies, 52 (61%) evaluated EBP skills, 39 (46%) knowledge, 35 (41%) attitudes, 19 (22%) behaviours, 15 (18%) self-efficacy, and 7 (8%) measured reactions to EBP teaching delivery. Of the 24 instruments used in the included studies, 6 were high-quality (achieved ≥3 types of established validity evidence) and these were used in 14 (29%) of the 52 studies that measured EBP skills; 14 (41%) of the 39 studies that measured EBP knowledge; and 8 (26%) of the 35 studies that measured EBP attitude. Conclusions Most EBP educational interventions which have been evaluated in controlled studies focus on teaching only some of the EBP steps (predominantly critically appraisal of evidence) and did not use high-quality instruments to measure outcomes. Educational packages and instruments which address all EBP steps are needed to improve EBP teaching

NmcA Carbapenem-hydrolyzing Enzyme in Enterobacter cloacae in North America1

An imipenem-resistant Enterobacter cloacae isolate was recovered from the blood of a patient with a hematologic malignancy. Analytical isoelectric focusing, inhibitor studies, hydrolysis, induction assays, and molecular sequencing methods confirmed the presence of a NmcA carbapenem-hydrolyzing enzyme. This first report of NmcA detected in North America warrants further investigation into its distribution and clinical impact

Novel chemical hazard characterisation approaches

There is a fundamental change in thinking within the regulatory community due to a better understanding of the underlying biology of adverse effects to human health and the environment. The development of alternatives to use laboratory animals has become a priority. In addition, technological progress is impacting greatly on the amount of data available and on the ways to process and analyse it. Topics, such as identification of adverse outcome pathways (AOPs) and modes of action (MoA), together with integrated assessment and testing approaches (IATAs), represent fundamental tools for hazard identification and characterisation of a chemical. Complex endpoints cannot be predicted by a single standalone non-animal test; thus, a major challenge is the complex nature of biological systems. Microphysiological systems (MPS) will enable more complex in vitro human models that better simulate the organ's biology and function by combining different cell types in a specific three-dimensional configuration that simulates functional organs. The process of validation of new approaches needs to be considered in terms of efficiency and length. Regulators might still not have enough confidence to adopt and apply these new approaches: this phase is very challenging and the activities performed by assay developers are not yet addressing the regulatory requirements needs sufficiently. The IATAs provide a framework to consistently evaluate new approach data and could assist in understanding their relevance for specific endpoints. The data need to be reproducible, understandable and statistically sound: indeed, a major issue lies in the interpretation and integration of the results based on subjective assessment, which relies on expert judgement. A well-defined mechanistic characterisation is proposed as a way forward to ensure the relevance of new cell-based test systems

Comparison of Two Commercial Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) Systems for Identification of Nontuberculous Mycobacteria.

Objectives: This multi-center study’s aim was to assess the performance of two commercially-available matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems in identifying a challenge collection of clinically-relevant nontuberculous mycobacteria (NTM). Methods: NTM clinical isolates (N=244) belonging to 23 species/subspecies were identified by gene sequencing and analyzed using the Bruker Biotyper with Mycobacterial Library v5.0.0 and the bioMérieux VITEK MS with v3.0 database. Results: Using the Bruker or bioMérieux systems, 92% or 95% of NTM strains, respectively, were identified at least to the complex/group level; 62% and 57%, respectively, were identified to the highest taxonomic level. Differentiation between members of the M. abscessus, M. fortuitum, M. mucogenicum, M. avium, and M. terrae complexes/groups was problematic for both systems, as was identification of M. chelonae for the Bruker system. Conclusions: Both systems identified most NTM isolates to the group/complex level, and many to the highest taxonomic level. Performance was comparable