Short-course antibiotic therapy for critically ill patients treated for postoperative intra-abdominal infection: the DURAPOP randomised clinical trial

PURPOSE: Shortening the duration of antibiotic therapy (ABT) is a key measure in antimicrobial stewardship. The optimal duration of ABT for treatment of postoperative intra-abdominal infections (PIAI) in critically ill patients is unknown. METHODS: A multicentre prospective randomised trial conducted in 21 French intensive care units (ICU) between May 2011 and February 2015 compared the efficacy and safety of 8-day versus 15-day antibiotic therapy in critically ill patients with PIAI. Among 410 eligible patients (adequate source control and ABT on day 0), 249 patients were randomly assigned on day 8 to either stop ABT immediately (n = 126) or to continue ABT until day 15 (n = 123). The primary endpoint was the number of antibiotic-free days between randomisation (day 8) and day 28. Secondary outcomes were death, ICU and hospital length of stay, emergence of multidrug-resistant (MDR) bacteria and reoperation rate, with 45-day follow-up. RESULTS: Patients treated for 8 days had a higher median number of antibiotic-free days than those treated for 15 days (15 [6-20] vs 12 [6-13] days, respectively; P < 0.0001) (Wilcoxon rank difference 4.99 days [95% CI 2.99-6.00; P < 0.0001). Equivalence was established in terms of 45-day mortality (rate difference 0.038, 95% CI - 0.013 to 0.061). Treatments did not differ in terms of ICU and hospital length of stay, emergence of MDR bacteria or reoperation rate, while subsequent drainages between day 8 and day 45 were observed following short-course ABT (P = 0.041). CONCLUSION: Short-course antibiotic therapy in critically ill ICU patients with PIAI reduces antibiotic exposure. Continuation of treatment until day 15 is not associated with any clinical benefit. CLINICALTRIALS. GOV IDENTIFIER: NCT01311765

Early-onset ventilator-associated pneumonia incidence in intensive care units: a surveillance-based study

ABSTRACT: BACKGROUND: The incidence of ventilator-associated pneumonia (VAP) within the first 48 hours of intensive care unit (ICU) stay has been poorly investigated. The objective was to estimate early-onset VAP occurrence in ICUs within 48 hours after admission. METHODS: We analyzed data from prospective surveillance between 01/01/2001 and 31/12/2009 in 11 ICUs of Lyon hospitals (France). The inclusion criteria were: first ICU admission, not hospitalized before admission, invasive mechanical ventilation during first ICU day, free of antibiotics at admission, and ICU stay >=48 hours. VAP was defined according to a national protocol. Its incidence was the number of events per 1,000 invasive mechanical ventilation-days. The Poisson regression model was fitted from day 2 (D2) to D8 to incident VAP to estimate the expected VAP incidence from D0 to D1 of ICU stay. RESULTS: Totally, 367 (10.8%) of 3,387 patients in 45,760 patient-days developed VAP within the first 9 days. The predicted cumulative VAP incidence at D0 and D1 was 5.3 (2.6-9.8) and 8.3 (6.1-11.1), respectively. The predicted cumulative VAP incidence was 23.0 (20.8-25.3) at D8. The proportion of missed VAP within 48 hours from admission was 11% (9%-17%). CONCLUSIONS: Our study indicates underestimation of early-onset VAP incidence in ICUs, if only VAP occurring [greater than or equal to]48 hours is considered to be hospital-acquired. Clinicians should be encouraged to develop a strategy for early detection after ICU admission

Advancing Drug Innovation for Neglected Diseases—Criteria for Lead Progression

The current drug R&D pipeline for most neglected diseases remains weak, and unlikely to support registration of novel drug classes that meet desired target product profiles in the short term. This calls for sustained investment as well as greater emphasis in the risky upstream drug discovery. Access to technologies, resources, and strong management as well as clear compound progression criteria are factors in the successful implementation of any collaborative drug discovery effort. We discuss how some of these factors have impacted drug discovery for tropical diseases within the past four decades, and highlight new opportunities and challenges through the virtual North–South drug discovery network as well as the rationale for greater participation of institutions in developing countries in product innovation. A set of criteria designed to facilitate compound progression from screening hits to drug candidate selection is presented to guide ongoing efforts

Indications of flow near maximum compression in layered deuterium-tritium implosions at the National Ignition Facility

An accurate understanding of burn dynamics in implosions of cryogenically layered deuterium (D) and tritium (T) filled capsules, obtained partly through precision diagnosis of these experiments, is essential for assessing the impediments to achieving ignition at the National Ignition Facility. We present measurements of neutrons from such implosions. The apparent ion temperatures T[subscript ion] are inferred from the variance of the primary neutron spectrum. Consistently higher DT than DD T[subscript ion] are observed and the difference is seen to increase with increasing apparent DT T[subscript ion]. The line-of-sight rms variations of both DD and DT T[subscript ion] are small, ∼ 150 eV, indicating an isotropic source. The DD neutron yields are consistently high relative to the DT neutron yields given the observed T[subscript ion]. Spatial and temporal variations of the DT temperature and density, DD-DT differential attenuation in the surrounding DT fuel, and fluid motion variations contribute to a DT T[subscript ion] greater than the DD T[subscript ion], but are in a one-dimensional model insufficient to explain the data. We hypothesize that in a three-dimensional interpretation, these effects combined could explain the results.Lawrence Livermore National Laboratory (Contract No. DE-AC52- 07NA27344

PRAISE: providing a roadmap for automated infection surveillance in Europe

Introduction: Healthcare-associated infections (HAI) are among the most common adverse events of medical care. Surveillance of HAI is a key component of successful infection prevention programmes. Conventional surveillance - manual chart review - is resource intensive and limited by concerns regarding interrater reliability. This has led to the development and use of automated surveillance (AS). Many AS systems are the product of in-house development efforts and heterogeneous in their design and methods. With this roadmap, the PRAISE network aims to provide guidance on how to move AS from the research setting to large-scale implementation, and how to ensure the delivery of surveillance data that are uniform and useful for improvement of quality of care. Methods: The PRAISE network brings together 30 experts from ten European countries. This roadmap is based on the outcome of two workshops, teleconference meetings and review by an independent panel of international experts. Results: This roadmap focuses on the surveillance of HAI within networks of healthcare facilities for the purpose of comparison, prevention and quality improvement initiatives. The roadmap does the following: discusses the selection of surveillance targets, different organizational and methodologic approaches and their advantages, disadvantages and risks; defines key performance requirements of AS systems and suggestions for their design; provides guidance on successful implementation and maintenance; and discusses areas of future research and training requirements for the infection prevention and related disciplines. The roadmap is supported by accompanying documents regarding the governance and information technology aspects of implementing AS. Conclusions: Large-scale implementation of AS requires guidance and coordination within and across surveillance networks. Transitions to large-scale AS entail redevelopment of surveillance methods and their interpretation, intensive dialogue with stakeholders and the investment of considerable resources. This roadmap can be used to guide future steps towards implementation, including designing solutions for AS and practical guidance checklists

Laser generated electron transport experiment in a novel wire nail target

The transport of high intensity (2x1020 W/cm2) laser generated relativistic electrons with a solid target has been studied in a novel geometry. The targets were 20 um diameter solid copper wires, coated with ~ 2um of titanium, with an 80 um diameter hemispherical termination. They were illuminated by an ~500fs, ~200J pulse of 1.053um laser light focused to a ~ 20um diameter spot centered on the flat face of the hemisphere. K-alpha fluorescence from the Cu and Ti regions was imaged together with extreme ultraviolet (X-UV) emission at 68 and 256eV. Results showed a quasi exponential decline in K-alpha emission along the wire over a distance of a few hundred microns from the laser focus, consistent with bulk Ohmic inhibition of the relativistic electron transport. Weaker Ka and X-UV emission on a longer scale length showed limb brightening suggesting a transition to enhanced transport at the surface of the wire

A Dual Channel X-ray Spectrometer for Fast Ignition Research

A new Dual Channel Highly Ordered Pyrolytic Graphite (DC-HOPG) x-ray spectrometer was developed to study laser-generated electron beam transport. The instrument uses a pair of graphite crystals and has the advantage of simultaneously detecting self emission from low-Z materials in first diffraction order and high-Z materials in second order. The emissions from the target are detected using a pair of parallel imaging plates positioned in a such way that the noise from background is minimized and the mosaic focusing is achieved. Initial tests of the diagnostic on Titan laser (I {approx} 10{sup 20} W/cm{sup 2}, {tau} = 0.7 ps) show excellent signal-to-noise ratio (SNR) > 1000 for the low energy channel and SNR > 400 for the high energy channel