Abstract
Background
High-level antibiotic consumption plays a critical role in the selection and spread of extended-spectrum beta-lactamase-producing
Enterobacteriaceae
(ESBL-E) in the ICU. ...Implementation of a stewardship program including a restrictive antibiotic policy was evaluated with respect to ESBL-E acquisition (carriage and infection).
Methods
We implemented a 2-year, before-and-after intervention study including all consecutive adult patients admitted for > 48 h in the medical-surgical 26-bed ICU of Guadeloupe University Hospital (French West Indies). A conventional strategy period (CSP) including a broad-spectrum antibiotic as initial empirical treatment, followed by de-escalation (period before), was compared to a restrictive strategy period (RSP) limiting broad-spectrum antibiotics and shortening their duration. Antibiotic therapy was delayed and initiated only after microbiological identification, except for septic shock, severe acute respiratory distress syndrome and meningitis (period after). A multivariate Cox proportional hazard regression model adjusted on propensity score values was performed. The main outcome was the median time of being ESBL-E-free in the ICU. Secondary outcome included all-cause ICU mortality.
Results
The study included 1541 patients: 738 in the CSP and 803 in the RSP. During the RSP, less patients were treated with antibiotics (46.8% vs. 57.9%;
p
< 0.01), treatment duration was shorter (5 vs. 6 days;
p
< 0.01), and administration of antibiotics targeting anaerobic pathogens significantly decreased (65.3% vs. 33.5%;
p
< 0.01) compared to the CSP. The incidence of ICU-acquired ESBL-E was lower (12.1% vs. 19%;
p
< 0.01) during the RSP. The median time of being ESBL-E-free was 22 days (95% CI 16-NA) in the RSP and 18 days (95% CI 16–21) in the CSP. After propensity score weighting and adjusted analysis, the median time of being ESBL-E-free was independently associated with the RSP (hazard ratio, 0.746 95% CI 0.575–0.968;
p
= 0.02, and hazard ratio 0.751 95% CI 0.578–0.977;
p
= 0.03, respectively). All-cause ICU mortality was lower in the RSP than in the CSP (22.5% vs. 28.6%;
p
< 0.01).
Conclusions
Implementation of a program including a restrictive antibiotic strategy is feasible and is associated with less ESBL-E acquisition in the ICU without any worsening of patient outcome.
During a 2014 outbreak, 450 patients with confirmed chikungunya virus infection were admitted to the University Hospital of Pointe-à-Pitre, Guadeloupe. Of these, 110 were nonpregnant adults; 42 had ...severe disease, and of those, 25 had severe sepsis or septic shock and 12 died. Severe sepsis may be a rare complication of chikungunya virus infection.
Highlights • Severe manifestations of Chikungunya virus infection affected a small number of patients compared to the entire infected population. • Most patients had previous underlying diseases and ...presented with acute exacerbations triggered by Chikungunya virus infection. • Encephalitis, Guillain-Barré syndrome and severe sepsis could to be directly related to Chikungunya virus.
Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could ...improve outcomes by reducing inflammation-mediated lung injury.
In this multicentre, double-blind, placebo-controlled trial, done at 43 centres in France, we randomly assigned patients (1:1) receiving invasive mechanical ventilation for up to 72 h with PCR confirmed COVID-19 and associated moderate-to-severe ARDS to receive either IVIG (2 g/kg over 4 days) or placebo. Random assignment was done with a web-based system and was stratified according to the participating centre and the duration of invasive mechanical ventilation before inclusion in the trial (<12 h, 12-24 h, and >24-72 h), and treatment was administered within the first 96 h of invasive mechanical ventilation. To minimise the risk of adverse events, the IVIG administration was divided into four perfusions of 0·5 g/kg each administered over at least 8 hours. Patients in the placebo group received an equivalent volume of sodium chloride 0·9% (10 mL/kg) over the same period. The primary outcome was the number of ventilation-free days by day 28, assessed according to the intention-to-treat principle. This trial was registered on ClinicalTrials.gov, NCT04350580.
Between April 3, and October 20, 2020, 146 patients (43 29% women) were eligible for inclusion and randomly assigned: 69 (47%) patients to the IVIG group and 77 (53%) to the placebo group. The intention-to-treat analysis showed no statistical difference in the median number of ventilation-free days at day 28 between the IVIG group (0·0 IQR 0·0-8·0) and the placebo group (0·0 0·0-6·0; difference estimate 0·0 0·0-0·0; p=0·21). Serious adverse events were more frequent in the IVIG group (78 events in 22 32% patients) than in the placebo group (47 events in 15 20% patients; p=0·089).
In patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials.
Programme Hospitalier de Recherche Clinique.
The Guillain-Barré syndrome (GBS) has been reported as a possible complication of acute chikungunya infection. The chikungunya epidemics, which occurred in Martinique and Guadeloupe in 2014, affected ...308,000 people in these two islands. GBS occurred during or immediately after acute chikungunya infection in 13 patients (10 men, three women; mean age: 61 years). Median time from acute chikungunya to GBS onset was 9 days. Twelve patients were treated with intravenous polyvalent immunoglobulins, nine of whom improved within 7 days. Five of 13 patients required mechanical ventilation. Two patients with severe GBS died. At 6 months of follow-up, 7/13 achieved a good functional recovery with no or minor residual symptoms. A 2-fold increase in incidence was observed during the year of chikungunya outbreak. This study supports prior reports suggesting that GBS may be a complication of chikungunya.
Introduction International guidelines include early nutritional support (≤48 hour after admission), 20–25 kcal/kg/day, and 1.2–2 g/kg/day protein at the acute phase of critical illness. Recent data ...challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets.Methods and analysis NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2–0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0–1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes.Ethics and dissemination The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals. Trial registration number NCT03573739 .
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