Purpose
The primary objective of this study was to investigate the risk of ICU bloodstream infection (BSI) in critically ill COVID-19 patients compared to non-COVID-19 patients. Subsequently, we ...performed secondary analyses in order to explain the observed results.
Methods
We conducted a matched case-cohort study, based on prospectively collected data from a large ICU cohort in France. Critically ill COVID-19 patients were matched with similar non-COVID-19 patients. ICU-BSI was defined by an infection onset occurring > 48 h after ICU admission. We estimated the effect of COVID-19 on the probability to develop an ICU-BSI using proportional subdistribution hazards models.
Results
We identified 321 COVID-19 patients and 1029 eligible controls in 6 ICUs. Finally, 235 COVID-19 patients were matched with 235 non-COVID-19 patients. We observed 43 ICU-BSIs, 35 (14.9%) in the COVID-19 group and 8 (3.4%) in the non-COVID-19 group (
p
≤ 0.0001), respectively. ICU-BSIs of COVID-19 patients were more frequently of unknown source (47.4%). COVID-19 patients had an increased probability to develop ICU-BSI, especially after 7 days of ICU admission. Using proportional subdistribution hazards models, COVID-19 increased the daily risk to develop ICU-BSI (sHR 4.50, 95% CI 1.82–11.16,
p
= 0.0012). Among COVID-19 patients (
n
= 235), a significantly increased risk for ICU-BSI was detected in patients who received tocilizumab or anakinra (sHR 3.20, 95% CI 1.31–7.81,
p
= 0.011) but not corticosteroids.
Conclusions
Using prospectively collected multicentric data, we showed that the ICU-BSI risk was higher for COVID-19 than non-COVID-19 critically ill patients after seven days of ICU stay. Clinicians should be particularly careful on late ICU-BSIs in COVID-19 patients. Tocilizumab or anakinra may increase the ICU-BSI risk.
Purpose
Amikacin requires pharmacodynamic targets of peak serum concentration (
C
max
) of 8–10 times the minimal inhibitory concentration, corresponding to a target
C
max
of 60–80 mg/L for the less ...susceptible bacteria. Even with new dosing regimens of 25 mg/kg, 30 % of patients do not meet the pharmacodynamic target. We aimed to identify predictive factors for insufficient
C
max
in a population of critically ill patients.
Methods
Prospective observational monocentric study of patients admitted to a general ICU and requiring a loading dose of amikacin. Amikacin was administered intravenously at the dose of 25 mg/kg of total body weight. Independent determinants of
C
max
< 60 mg/L were identified by mixed model multivariate analysis.
Results
Over a 1-year period, 181 episodes in 146 patients (SAPS 2 = 51 41–68) were included. At inclusion, the SOFA score was 8 6–12, 119 (66 %) episodes required vasopressors, 150 (83 %) mechanical ventilation, and 81 (45 %) renal replacement therapy. The amikacin
C
max
was 69 54.9–84.4 mg/L. Overall, 60 (33 %) episodes had a
C
max
< 60 mg/L. The risk of
C
max
< 60 mg/L associated with BMI < 25 kg/m
2
varied across quarters of inclusion. Independent risk factors for
C
max
< 60 mg/L were a BMI < 25 kg/m
2
over the first quarter (odds ratio (OR) 15.95, 95 % confidence interval (CI) 3.68–69.20,
p
< 0.001) and positive 24-h fluid balance (OR per 250-mL increment 1.06, 95 % CI 1.01–1.11,
p
= 0.018).
Conclusions
Despite an amikacin dose of 25 mg/kg of total body weight, 33 % of patients still had an amikacin
C
max
< 60 mg/L. Positive 24-h fluid balance was identified as a predictive factor of
C
max
< 60 mg/L. When total body weight is used, low BMI tended to be associated with amikacin underdosing. These results suggest the need for higher doses in patients with a positive 24-h fluid balance in order to reach adequate therapeutic targets.
Purpose
To investigate the clinical significance of infection-related ventilator-associated complications (IVAC) and their impact on carbapenem consumption in mechanically ventilated (MV) patients ...colonised with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLE).
Methods
Inception cohort study from the French prospective multicenter OUTCOMEREA database (17 ICUs, 1997–2015) including all ESBLE carriers (systematic rectal swabbing at admission then weekly and/or urinary or superficial surgical site colonisation) with MV duration > 48 h and ≥ 1 episode of IVAC after carriage documentation. All ICU-acquired infections were microbiologically documented.
Results
The 318 enrolled ESBLE carriers (median age 68 years; males 67%; medical admission 68%; imported carriage 53%) experienced a total of 576 IVAC comprising 361 episodes (63%) without documented infection, 124 (21%) related to infections other than ventilator-associated pneumonia (VAP), 73 (13%) related to non-ESBLE VAP and 18 (3%) related to ESBLE VAP. Overall, ESBLE infections accounted for only 43 episodes (7%). Carbapenem exposure within the preceding 3 days was the sole independent predictor of ESBLE infection as the causative event of IVAC, with a protective effect (adjusted odds ratio 0.2, 95% confidence interval 0.05–0.6;
P
< 0.01). Carbapenems were initiated in 9% of IVAC without infection, 15% of IVAC related to non-VAP infections, 42% of IVAC related to non-ESBLE VAP, and 56% of IVAC related to ESBLE VAP (ESBLE VAP versus non-ESBLE VAP:
P
= 0.43).
Conclusions
IVAC in ESBLE carriers mostly reflect noninfectious events but act as a strong driver of empirical carbapenem consumption. ESBLE infections are scarce yet hard to predict, strengthening the need for novel diagnostic approaches and carbapenem-sparing alternatives.
Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a frequent cause of intensive care unit (ICU) admission. However, data are scarce and conflicting regarding the impact of ...systemic corticosteroid treatment in critically ill patients with acute exacerbation of COPD. The aim of the study was to assess the impact of systemic corticosteroids on the occurrence of death or need for continuous invasive mechanical ventilation at day 28 after ICU admission.
In the OutcomeReaTM prospective French national ICU database, we assessed the impact of corticosteroids at admission (daily dose ≥ 0.5 mg/kg of prednisone or equivalent during the first 24 hours ICU stay) on a composite outcome (death or invasive mechanical ventilation) using an inverse probability treatment weighting.
Between January 1, 1997 and December 31, 2018, 391 out of 1,247 patients with acute exacerbations of COPDs received corticosteroids at ICU admission. Corticosteroids improved the main composite endpoint (OR = 0.70 0.49; 0.99, p = 0.044. However, for the subgroup of most severe COPD patients, this did not occur (OR = 1.12 0.53; 2.36, p = 0. 770). There was no significant impact of corticosteroids on rates of non-invasive ventilation failure, length of ICU or hospital stay, mortality or on the duration of mechanical ventilation. Patients on corticosteroids had the same prevalence of nosocomial infections as those without corticosteroids, but more glycaemic disorders.
Using systemic corticosteroids for acute exacerbation of COPD at ICU admission had a positive effect on a composite outcome defined by death or need for invasive mechanical ventilation at day 28.
Background
Sepsis is one of the leading causes of death worldwide. The associated incidence, mortality and trends do not differ greatly between documented reports. The purpose of this study was to ...provide an in-depth description of patients with sepsis and septic shock hospitalized in France from 2010 to 2015 and to explore the temporal trends of their clinical characteristics, costs and outcomes.
Methods
Retrospective cohort study of the French hospital administrative database in which organ failure therapies and severity scores are systematically registered. All patients admitted between 2010 and 2015 for sepsis and septic shock as defined by an ICD-10 code for infection, and for organ failure or the use of organ failure supplementation were included. Incidence, outcomes and trends were analyzed. Subgroup analyses based on several coding strategies and adjusted for severity scores were performed.
Results
A total of 737,147 patients with sepsis and 492,902 patients with septic shock were included. From 2010 to 2015, the incidence of sepsis and septic shock increased, respectively, from 206 to 243 and from 135 to 171 cases per 100,000 population. Case fatality remained at 34% for sepsis, but decreased from 46 to 44% for septic shock.
Median hospital stay costs amounted to €11,400 (IQR: 5036; 24,364) for patients with sepsis and €16,439 (IQR: 7339; 29,360) for patients with septic shock.
After adjustment for case-mix and illness severity, the risk of death was stable for sepsis (0.08% − 0.04; 0.20 per year), but decreased for sepsis patients admitted to the intensive care unit and for cases of septic shock (− 0.33% − 0.40; − 0.27 per year).
Conclusions
Sepsis is common, frequently fatal and expensive to treat. Its incidence has increased. Case fatality has decreased in most severely affected patients, owing partly to general improvements in care.
Purpose
In ICU patients with carriage of extended spectrum beta-lactamase producing
Enterobacterales
(ESBL-E) and suspected Gram-negative bacilli ventilator-associated pneumonia (GNB-VAP), the ...quantification of the rectal and throat ESBL-E carriage might predict the ESBL-E involvement in GNB-VAP. Our aim was to evaluate whether a semi-quantitative assessment of rectal/throat ESBL-E carriage can predict ESBL-E-associated VAP in medical ICU patients.
Methods
From May 2014 to May 2017, all ESBL-E carriers had a semi-quantitative assessment of ESBL-E density in swabs cultures. For those who developed GNB-VAP (diagnosed using bronchoalveolar lavage or plugged telescopic catheter with significant quantitative culture), the last positive swab collected at least 48 h before GNB-VAP onset was selected. Clinical data were extracted from a prospectively collected database.
Results
Among 365 ESBL-E carriers, 82 developed 107 episodes of GNB-VAP (ESBL-E VAP,
n
= 50; and non-ESBL-E GNB-VAP,
n
= 57) after 13 days of mechanical ventilation in median. Antimicrobials use before VAP onset was similar between groups. The last swabs were collected 5 days in median before VAP onset. ESBL-
E. coli
carriers developed ESBL-E VAP less frequently (
n
= 13, 34%) than others (
n
= 32, 67.3%,
p
< .01). Throat swab positivity (39 (78%) vs. 12 (23%),
p
< .01) was more frequent for ESBL-E VAP. ESBL-E VAP was associated with significantly higher ESBL-E density in rectal swabs. In multivariate models, non-
E. coli
ESBL-E carriage and rectal ESBL-E carriage density, or throat carriage, remained associated with ESBL-E VAP.
Conclusion
In carriers of ESBL-E other than
E. coli,
ESBL-E throat carriage or a high-density ESBL-E rectal carriage are risk factors of ESBL-E VAP in case of GNB-VAP.
We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19 in Europe. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was ...detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2–3-fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in γδ T cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a pro-inflammatory cytokine storm, Th1 and Th2 activation, and markers of T cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response. The investigation was conducted as part of an overall French clinical cohort assessing patients with COVID-19 and registered in
clinicaltrials.gov
under the following number: NCT04262921.
Purpose
Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes.
Methods
We conducted a retrospective analysis of a prospective multicenter ...database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively.
Results
We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19–1.67, hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27–5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09–1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53–2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48–3.57), and
S. aureus
(aOR = 1.54, 95% CI 1.05–2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13–14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09–1.76).
Conclusions
Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.
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