Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial.

Background: Nosocomial pneumonia is commonly associated with antimicrobial-resistant Gram-negative pathogens. We aimed to assess the efficacy and safety of ceftazidime-avibactam in patients with nosocomial pneumonia, including ventilator-associated pneumonia, compared with meropenem in a multinational, phase 3, double-blind, non-inferiority trial (REPROVE).

Methods: Adults with nosocomial pneumonia (including ventilator-associated pneumonia), enrolled at 136 centres in 23 countries, were randomly assigned (1:1) to 2000 mg ceftazidime and 500 mg avibactam (by 2 h intravenous infusion every 8 h) or 1000 mg meropenem (by 30-min intravenous infusion every 8 h) for 7-14 days; regimens were adjusted for renal function.

Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program.

Background: When combined with ceftazidime, the novel non-β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239).

Methods: The primary end point was clinical cure at test-of-cure visit 28-35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance).

A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation.

Objectives: To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation.

Design: Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial.

Setting: Two hundred and thirty-three ICUs in 17 countries.

Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial.

Importance: Eritoran is a synthetic lipid A antagonist that blocks lipopolysaccharide (LPS) from binding at the cell surface MD2-TLR4 receptor. LPS is a major component of the outer membrane of gram-negative bacteria and is a potent activator of the acute inflammatory response.

Objective: To determine if eritoran, a TLR4 antagonist, would significantly reduce sepsis-induced mortality.

Efficacy and safety of anidulafungin in elderly, critically ill patients with invasive Candida infections: a post hoc analysis.

Post hoc analysis of a non-comparative, prospective, multicentre, phase IIIb study was performed to compare efficacy and safety of anidulafungin in elderly (≥65 years) versus non-elderly (<65 years) Intensive Care Unit (ICU) patients with candidaemia/invasive candidiasis (C/IC). Adult ICU patients with confirmed C/IC meeting ≥1 of the following criteria were enrolled: post-abdominal surgery; solid tumour; renal/hepatic insufficiency; solid organ transplantation; neutropenia; age ≥65 years. Patients received anidulafungin (200 mg on Day 1, 100 mg/day thereafter) for ≥10 days followed by optional azole step-down therapy for a total treatment duration of 14-56 days.

Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness).

Background: Transnasal evaporative cooling has sufficient heat transfer capacity for effective intra-arrest cooling and improves survival in swine. The aim of this study was to determine the safety, feasibility, and cooling efficacy of prehospital transnasal cooling in humans and to explore its effects on neurologically intact survival to hospital discharge.

Methods And Results: Witnessed cardiac arrest patients with a treatment interval View Article and Find Full Text PDF

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury.

Background: Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury.

Frequent intravenous pulses of growth hormone together with glutamine supplementation in prolonged critical illness after multiple trauma: effects on nitrogen balance, insulin resistance, and substrate oxidation.

Objectives: To estimate the efficacy and metabolic effects of growth hormone substitution as intravenous pulses together with alanyl-glutamine supplementation and tight blood glucose control in prolonged critical illness.

Design: Prospective double-blind, randomized trial with open-label control arm.

Setting: Intensive care unit of tertiary level hospital.

Dymanics of matrix-metalloproteinase 9 after brain trauma--results of a pilot study.

Background: Secondary brain injury contributes to poor outcome for patients sustaining brain trauma. Matrix metalloproteinase-9 (MMP-9) is a potential marker, as well as effector of secondary brain injury. This enzyme degrades components of extracellular matrix, and thus it can contribute to blood-brain barrier disruption.

Frequent intravenous pulses of growth hormone together with alanylglutamine supplementation in prolonged critical illness after multiple trauma: effects on glucose control, plasma IGF-I and glutamine.

Objective: We aim to demonstrate that low dose growth hormone (GH) administered in i.v. pulses every 3h is able to normalize IGF-I levels in subjects with prolonged critical illness, after multiple trauma.

A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis.

Background: Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species.

Methods: A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs.

Parenterally administered dipeptide alanyl-glutamine prevents worsening of insulin sensitivity in multiple-trauma patients.

Background: Dipeptide alanyl-glutamine is a commonly used substrate in major trauma patients. Its importance and effects are widely discussed; as yet, it has not been elucidated whether its administration influences glucose homeostasis.

Objective: We studied the effect of alanyl-glutamine administration on insulin resistance.

Changes in cholesterol and its precursors during the first days after major trauma.

Background: The causes of hypocholesterolemia in the critically ill, including major trauma patients, have not yet been fully elucidated.

Objective: We tested the hypothesis that hypocholesterolemia is caused by decreased production of cholesterol precursors.

Design: Serum concentrations of squalene, lanosterol, and lathosterol were measured on admission, and then at 24 and 48 hours after injury using gas chromatography coupled with mass spectrometry.

Relationship between natriuretic peptides and residual diuresis during continuous hemodiafiltration.

Background: The reasons for the decrease or increase of urine output following the start of continuous venovenous hemodiafiltration (CVVHDF) have not yet been explained sufficiently. The renoprotective properties of natriuretic peptides were described.

Methods: The levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured in 23 mechanically ventilated patients before and during the first 48 h of CVVHDF.

Effect of the degree of tricuspid regurgitation on cardiac output measurements by thermodilution.

Objective: To determine the relationship between the degree of tricuspid regurgitation (TR) and accuracy of cardiac output measurement by thermodilution in mechanically ventilated patients. DESIGN AND SETTING. Prospective observational study in a 20-bed general intensive care unit in the university hospital.