Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives:We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT(> MIC) (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving beta-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of >= 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025].Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Contenido de sulforafano (1-isotiocianato-4-(metilsulfinil)-butano) en vegetales crucíferos

El sulforafano es un isotiocianato con propiedades antimicrobianas y anticarcinogénicas, se encuentra en una amplia variedad de vegetales del género Brassica oleracea, considerándose las más importantes el brócoli y repollo. El objetivo de esta investigación fue cuantificar sulforafano en las partes comestibles de brócoli y en hojas de repollo por cromatografía líquida de alta resolución (HPLC). La preparación de la muestra para la cuantificación del sulforafano incluye la conversión de glucorafanina a sulforafano (45 ± 2°C durante 2,5 h), extracción con diclorometano, purificación del extracto en columnas de extracción de fase sólida, y detección por HPLC-UV. En brócoli la concentración de sulforafano está en el rango de 214 µg/g bs (tallos) a 499 µg/g bs (inflorescencias). El repollo morado (101,99 µg/g bs) presentó valores mayores de sulforafano que el repollo verde (7,58 µg/g bs). Las inflorescencias de brócoli y las hojas de repollo morado son ricos en sulforafano

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged- infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT 65MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving \u3b2-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of 65 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025]. Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections. \ua9 The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

DALI: Defining antibiotic levels in intensive care unit patients: Are current ß-lactam antibiotic doses sufficient for critically ill patients?

Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether α-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome.Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 α-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% f TMIC) and 100% (100% f T MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome.Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f TMIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P =. 009). Positive clinical outcome was associated with increasing 50% f TMIC and 100% f TMIC ratios (OR, 1.02 and 1.56, respectively; P <. 03), with significant interaction with sickness severity status.Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved

Variability In Protein Binding Of Teicoplanin And Achievement Of Therapeutic Drug Monitoring Targets In Critically Ill Patients: Lessons From The Dali Study

The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6(11.2-26.0) and free 1.5 (0.7-2.5); trough, total 11.9 (10.2-22.7) and free 1.8 (0.6-2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5-15.6%) and 8.2% (5.5-16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (rho=0.79, P = 0.0021) and trough (rho = 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients. (C) 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.Wo

Dali: Defining Antibiotic Levels In Intensive Care Unit Patients: Are Current Beta-Lactam Antibiotic Doses Sufficient For Critically Ill Patients?

Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether beta-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome. Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 beta-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% sic T-> MIC) and 100% (100% sic T > MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome. Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% sic T-> MIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P =.009). Positive clinical outcome was associated with increasing 50% sic T-> MIC and 100% sic T-> MIC ratios (OR, 1.02 and 1.56, respectively; P <.03), with significant interaction with sickness severity status. Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.WoSScopu

SuperB Detector technical design Report

In this Technical Design Report (TDR) we describe the SuperB detector that was to be installed on the SuperB e+e- high luminosity collider. The SuperB asymmetric collider, which was to be constructed on the Tor Vergata campus near the INFN Frascati National Laboratory, was designed to operate both at the Upsilon(4S) center-of-mass energy with a luminosity of 10^36 cm^-2s^-1 and at the tau/charm production threshold with a luminosity of 10^35 cm^-2s^-1. This high luminosity, producing a data sample about a factor 100 larger than present B Factories, would allow investigation of new physics effects in rare decays, CP Violation and Lepton Flavour Violation. This document details the detector design presented in the Conceptual Design Report (CDR) in 2007. The R&D and engineering studies performed to arrive at the full detector design are described, and an updated cost estimate is presented. A combination of a more realistic cost estimates and the unavailability of funds due of the global economic climate led to a formal cancelation of the project on Nov 27, 2012