Dataset Information

Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial.

ABSTRACT: Background:Appropriate antimicrobial dosing is challenging because of changes in pharmacokinetics (PK) parameters and an increase in multidrug-resistant (MDR) organisms in critically ill patients. This study aimed to evaluate the effects of an empirical therapy of high-dose versus standard-dose meropenem in sepsis and septic shock patients. Methods:We performed a prospective randomized open-label study to compare the changes of modified sequential organ failure assessment (mSOFA) score and other clinical outcomes of the high-dose meropenem (2-g infusion over 3?h every 8?h) versus the standard-dose meropenem (1-g infusion over 3?h every 8?h) in sepsis and septic shock patients. Patients' characteristics, clinical and microbiological outcomes, 14 and 28-day mortality, vasopressor- and ventilator-free days, intensive care unit (ICU) and hospital-free days, percent of the time of antibiotic concentrations above the minimum inhibitory concentration (%T>MIC), and safety were assessed. Results:Seventy-eight patients were enrolled. Median delta mSOFA was comparable between two groups (-?1 in the high-dose group vs. -?1 in the standard-dose group; P value = 0.75). There was no difference between the two groups regarding clinical and microbiological cure, 14- and 28-day mortality, vasopressor- and ventilator-free days, and ICU- and hospital-free days. In patients admitted from the emergency department (ED) with a mSOFA score ??7, the high-dose group demonstrated significantly better microbiological cure compared with the standard-dose group (75% (9/12 patients) vs. 20% (2/10 patients); P value = 0.03). Likewise, the high-dose group presented higher microbiological cure rate in patients admitted from ED who had either APACHE II score >?20 (83.3% (10/12) vs. 28.6% (2/7); P value = 0.045) or on mechanical ventilator (87.5% (7/8) vs. 23.1% (3/13); P value = 0.008) than the standard-dose group. Adverse events were comparable between the two groups. Conclusions:Empirical therapy with the high-dose meropenem presented comparable clinical outcomes to the standard-dose meropenem in sepsis and septic shock patients. Besides, subgroup analysis manifested superior microbiological cure rate in sepsis or septic shock patients admitted from ED. Trial registration:ClinicalTrials.gov, NCT03344627, registered on November 17, 2017.

SUBMITTER: Lertwattanachai T

PROVIDER: S-EPMC7158081 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial.

Lertwattanachai Tospon T Montakantikul Preecha P Tangsujaritvijit Viratch V Sanguanwit Pitsucha P Sueajai Jetjamnong J Auparakkitanon Saranya S Dilokpattanamongkol Pitchaya P

Journal of intensive care 20200415

<h4>Background</h4>Appropriate antimicrobial dosing is challenging because of changes in pharmacokinetics (PK) parameters and an increase in multidrug-resistant (MDR) organisms in critically ill patients. This study aimed to evaluate the effects of an empirical therapy of high-dose versus standard-dose meropenem in sepsis and septic shock patients.<h4>Methods</h4>We performed a prospective randomized open-label study to compare the changes of modified sequential organ failure assessment (mSOFA) ...[more]

PMID: 32318268

Similar Datasets

Project description:AimsSepsis-induced cardiomyopathy is a major complication of septic shock and contributes to its high mortality. This pilot study investigated myocardial tissue differentiation in critically ill, sedated, and ventilated patients with septic shock using cardiovascular magnetic resonance (MR).Methods and resultsFifteen patients with septic shock were prospectively recruited from the intensive care unit. Individuals received a cardiac MR scan (1.5 T) within 48 h after initial catecholamine peak and a transthoracic echocardiography at 48 and 96 h after cardiac MR. Left ventricular ejection fraction was assessed using both imaging modalities. During cardiac MR imaging, balanced steady-state free precession imaging was performed for evaluation of cardiac anatomy and function in long-axis and short-axis views. Native T1 maps (modified Look-Locker inversion recovery 5 s(3 s)3 s), T2 maps, and extracellular volume maps were acquired in mid-ventricular short axis and assessed for average plane values. Patients were given 0.2 mmol/kg of gadoteridol for extracellular volume quantification and late gadolinium enhancement imaging. Critical care physicians monitored sedated and ventilated patients during the scan with continuous invasive monitoring and realized breathholds through manual ventilation breaks. Laboratory analysis included high-sensitive troponine T and N terminal pro brain natriuretic peptide levels. Twelve individuals with complete datasets were available for analysis (age 59.5 ± 16.9 years; 6 female). Nine patients had impaired systolic function with left ventricular ejection fraction (LVEF) < 50% (39.8 ± 5.7%), and three individuals had preserved LVEF (66.9 ± 6.7%). Global longitudinal strain was impaired in both subgroups (LVEF impaired: 11.0 ± 1.8%; LVEF preserved: 16.0 ± 5.8%; P = 0.1). All patients with initially preserved LVEF died during hospital stay; in-hospital mortality with initially impaired LVEF was 11%. Upon echocardiographic follow-up, LVEF improved in all previously impaired patients at 48 (52.3 ± 9.0%, P = 0.06) and 96 h (54.9 ± 7.0%, P = 0.02). Patients with impaired systolic function had increased T2 times as compared with patients with preserved LVEF (60.8 ± 5.6 ms vs. 52.2 ± 2.8 ms; P = 0.02). Left ventricular GLS was decreased in all study individuals with impaired LVEF (11.0 ± 1.8%) and less impaired with preserved LVEF (16.0 ± 5.8%; P = 0.01). T1 mapping showed increased T1 times in patients with LVEF impairment as compared with patients with preserved LVEF (1093.9 ± 86.6 ms vs. 987.7 ± 69.3 ms; P = 0.03). Extracellular volume values were elevated in patients with LVEF impairment (27.9 ± 2.1%) as compared with patients with preserved LVEF (22.7 ± 1.9%; P < 0.01).ConclusionsSeptic cardiomyopathy with impaired LVEF reflects inflammatory cardiomyopathy. Takotsubo-like contractility patterns occur in some cases. Cardiac MR is safely feasible in critically ill, sedated, and ventilated patients using extensive monitoring and experienced staff.Trial registrationretrospectively registered (ISRCTN85297773).

Project description:Sepsis is commonly associated with acute kidney injury (AKI), particularly in those requiring dialysis (AKI-D). To date, Sepsis-3 criteria have not been applied to AKI-D patients. We investigated sepsis prevalence defined by Sepsis-3 criteria and evaluated the outcomes of septic-associated AKI-D among critically ill patients. Using the data collected from a prospective multi-center observational study, we applied the Sepsis-3 criteria to critically ill AKI-D patients treated in intensive care units (ICUs) in 30 hospitals between September 2014 and December 2015. We described the prevalence, outcomes, and characteristics of sepsis as defined by the screening Sepsis-3 criteria among AKI-D patients, and compared the outcomes of AKI-D patients with or without sepsis using the Sepsis-3 criteria. A total of 1078 patients (median 70 years; 673 (62.4%) men) with AKI-D were analyzed. The main etiology of AKI was sepsis (71.43%) and the most frequent indication for acute dialysis was oliguria (64.4%). A total of 577 (53.3% of 1078 patients) met the Sepsis-3 criteria, and 206 among the 577 patients (19.1%) had septic shock. Having sepsis and septic shock were independently associated with 90-day mortality among these ICU AKI-D patients (hazard ratio (HR) 1.23 (p = 0.027) and 1.39 (p = 0.004), respectively). Taking mortality as a competing risk factor, AKI-D patients with septic shock had a significantly reduced chance of weaning from dialysis at 90 days than those without sepsis (HR 0.65, p = 0.026). The combination of the Sepsis-3 criteria with the AKI risk score led to better performance in forecasting 90-day mortality. Sepsis affects more than 50% of ICU AKI patients requiring dialysis, and one-fifth of these patients had septic shock. In AKI-D patients, coexistent with or induced by sepsis (as screened by the Sepsis-3 criteria), there is a significantly higher mortality and reduced chance of recovering sufficient renal function, when compared to those without sepsis.

Project description:BackgroundProteinuria results from kidney damage and can be a predictor of illness severity and mortality in the intensive care unit (ICU). However, the optimal timing of proteinuria measurements and the reference values remain undetermined. Our objective was to identify the patterns of proteinuria change associated with mortality in ICU patients with sepsis or shock.MethodsThis monocentric retrospective cohort study performed from April 2010 to April 2018 involved all ICU patients with sepsis or shock and at least two measurements of proteinuria from a 24h-urine collection during the first 10 days of ICU stay, the first of which was made within 48h after ICU admission. We identified proteinuria trajectories by a semi-parametric mixture model and analysed the association between the trajectories and the mortality at day 28 by Cox proportional-hazards model.ResultsA total of 3,344 measurements of proteinuria from 659 patients were analysed. Four proteinuria trajectories were identified. Trajectories 1, 2, 3 and 4 comprised 127, 421, 60 and 51 patients, and were characterized by a first proteinuria of 1.14 [0.66-1.55], 0.52 [0.26-0.91], 2.92 [2.38-3.84] and 2.58 [1.75-3.32] g/24h (p<0.001) and a mortality of 24.4%, 38%, 20% and 43% (p = 0.002), respectively. Trajectories 3 and 4 had a high first proteinuria (>2g/24h). Only, the proteinuria of trajectory 4 increased within 3 days following the first measurement and was associated with increased mortality at day 28 (hazard ratio: 2.36 95%CI [1.07-5.19], p = 0.03), regardless of acute renal failure. The factors associated with trajectory 4 were cancer (relative risk: 8.91 95%CI [2.09-38.02], p = 0.003) and use of inotropic drugs (relative risk: 0.17 95%CI [0.04-0.69], p = 0.01).ConclusionThis exploratory study of ICU patients with sepsis or shock identified four proteinuria trajectories with distinct patterns of proteinuria change over time and mortality rates. These results provide novel insights into renal pathophysiology and may be helpful to investigate subphenotypes of kidney injury among ICU patients in future studies.

Project description:Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyteÂ® Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyteÂ® Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyteÂ® Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyteÂ® Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyteÂ® Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyteÂ® Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation. SIRS and Sepsis ICU patients, admission samples Retrospective, mutli-site sutdy using retrospective physician adjudication as a comparator

Dataset Information

Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial.

Publications

Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets