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1.
Infect Dis Ther ; 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33586088

RESUMO

INTRODUCTION: Available evidence from observational studies and meta-analyses has highlighted an increased mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSI) compared with their carbapenem-susceptible (CSKP) counterparts, but the exact reasons for this outcome difference are still to be determined. METHODS: We updated the search of a previous meta-analysis through four databases up to April 2018. A two-stage individual-patient data (IPD) meta-analysis was conducted, building an adjusting model to account for age, comorbidities and activity of empirical and targeted antimicrobial therapy. The protocol was registered on PROSPERO (identifier: CRD42018104256). RESULTS: IPD data were obtained from 14 out of 28 eligible observational studies. A total of 1952 patients were investigated: 1093 in the CRKP group and 859 in the CSKP group. Patients with CRKP-BSI had a twofold risk of death compared with CSKP-infected patients [adjusted odds ratio (aOR) 2.17; 95% confidence interval (CI) 1.56-3.04; I2 = 44.1%]. Mortality was higher in patients with CRKP BSI, in both the subgroup of absent/inactive (aOR 1.75; 95% CI 1.24-2.47; I2 = 0) and of active initial therapy (aOR 2.66; 95% CI 1.70-4.16; I2 = 16%) as well as in case of active targeted therapy (aOR 2.21; 95% CI 1.36-3.59; I2 = 58%). CONCLUSION: Resistance to carbapenem is associated with worse outcome in patients with BSI by Klebsiella pneumoniae even adjusting for comorbidities and treatment appropriateness according to in vitro activity of empirical and targeted therapy. This applies to a scenario dominated by colistin-based therapies for CRKP. Further studies are needed to compare the mortality difference between CRKP and CSKP cases in the light of new anti-CRKP antimicrobials.

2.
Crit Care Med ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33591021

RESUMO

CONTEXT: Delayed awakening after sedation interruption is frequent in critically ill patients receiving mechanical ventilation. OBJECTIVES: We aimed to investigate the association of standard electroencephalography with mortality and command following in this setting. DESIGN, SETTING, AND PATIENTS: In a single-center study, we retrospectively analyzed standard electroencephalography performed in consecutive mechanically ventilated patients remaining unresponsive (comatose/stuporous or unable to follow commands) after sedation interruption. Standard electroencephalography parameters (background activity, continuity, and reactivity) were reassessed by neurophysiologists, blinded to patients' outcome. Patients were categorized during follow-up into three groups based on their best examination as: 1) command following, 2) unresponsive, or 3) deceased. Cause-specific models were used to identify independent standard electroencephalography parameters associated with main outcomes, that is, mortality and command following. Follow-up was right-censored 30 days after standard electroencephalography. MEASUREMENTS AND MAIN RESULTS: Main standard electroencephalography parameters recorded in 121 unresponsive patients (median time between sedation interruption and standard electroencephalography: 2 d [interquartile range, 1-4 d]) consisted of a background frequency greater than 4 Hz in 71 (59%), a discontinuous background in 19 (16%), and a preserved reactivity in 98/120 (82%) patients. At 30 days, 66 patients (55%) were command following, nine (7%) were unresponsive, and 46 (38%) had died. In a multivariate analysis adjusted for nonneurologic organ failure, a reactive standard electroencephalography with a background frequency greater than 4 Hz was independently associated with a reduced risk of death (cause-specific hazard ratio, 0.38; CI 95%, 0.16-0.9). By contrast, none of the standard electroencephalography parameters were independently associated with command following. Sensitivity analyses conducted after exclusion of 29 patients with hypoxic brain injury revealed similar findings. CONCLUSIONS: In patients remaining unresponsive after sedation interruption, a pattern consisting of a reactive standard electroencephalography with a background frequency greater than 4 Hz was associated with decreased odds of death. None of the standard electroencephalography parameters were independently associated with command following.

3.
Mayo Clin Proc ; 96(2): 295-303, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33549252

RESUMO

OBJECTIVE: To evaluate the clinical course of and risk factors for arterial thrombotic events in adult inpatients with coronavirus disease 2019 (COVID-19). METHODS: All consecutive adult patients admitted for COVID-19 infection in a referral center in France and discharged from the hospital between April 1 and April 30, 2020, were included. All arterial thrombotic events that occurred through discharge were considered for analysis. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records with use of a standardized data collection form. RESULTS: Overall, 531 COVID-19+ patients were analyzed. Among them, 30 (5.6%) experienced arterial thrombotic events. Arterial thrombotic events in the setting of COVID-19 infection happened at a median of 11 (5-20) days after the first symptoms of infection; occurred in high-risk patients according to traditional cardiovascular risk factors; had an atypical pattern, such as thrombosis of the aorta, upper limb, or renal arteries or cerebral microvasculopathy in 7 (23.3%) cases; and were associated with an in-hospital mortality rate of 40%. Arterial thrombotic events increased the risk of death by 3-fold in COVID-19+ patients (hazard ratio, 2.96; 95% CI, 1.4 to 4.7; P=.002). A subdistribution survival hazard model showed that a concentration of D-dimer above 1250 ng/mL increased the risk of arterial thrombotic events in COVID-19+ patients by more than 7 (subdistribution hazard ratio, 7.68; 95% CI, 2.9 to 20.6; P<.001). CONCLUSION: A dramatically high rate of in-hospital death was observed in patients who suffered arterial thrombotic events in the setting of COVID-19 infection. A D-dimer level above 1250 ng/mL at entry may identify COVID-19+ patients at risk for arterial thrombotic events.


Assuntos
/complicações , Trombose/etiologia , Idoso , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombose/epidemiologia
4.
Intensive Care Med ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33521871

RESUMO

PURPOSE: Obesity increases the risk of nosocomial infection, but data regarding the role of body mass index (BMI) in catheter related infections are scarce. We used the data gathered from four randomized, controlled trials (RCTs) to investigate the association between body mass index (BMI) and intravascular catheter infections in critically ill obese patients. METHODS: Adult obese patients who required short-term central venous, arterial or dialysis catheter insertion in the intensive care unit (ICU) were analyzed. The association between BMI and major catheter-related infection (MCRI), catheter-related bloodstream infection (CRBSI) and catheter tip colonization was estimated using univariate and multivariate marginal Cox models. Exploratory analysis using dressing disruptions was added. RESULTS: A total of 2282 obese patients and 4275 catheters from 32 centers were included in this post-hoc analysis. Overall, 66 (1.5%) MCRI, 43 (1%) CRBSI and 399 (9.3%) catheter colonizations were identified. The hazard ratio (HR) for MCRI, CRBSI and colonization increased with BMI. After adjustment for well-known infection risk factors, the BMI ≥ 40 group had an increased risk for MCRI (HR 1.88, 95% CI 1.13-3.12, p = 0.015), CRBSI (HR 2.19, 95% CI 1.19-4.04, p = 0.012) and colonization (HR 1.44, 95% CI 1.12-1.84, p = 0.0038) compared to the BMI < 40 group. The mean dressing disruption per catheter was increased in the BMI ≥ 40 group (2.03 versus 1.68 in the BMI < 40 group, p = 0.05). CONCLUSIONS: Using the largest dataset ever collected from large multicentric RCTs, we showed that patients with BMI ≥ 40 had an increased risk for intravascular catheter infections. Targeted prevention measures should focus on this population with a particular attention to catheter care and dressing disruption.

6.
Intensive Care Med ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616696

RESUMO

Coronavirus disease 19 (COVID-19) has posed unprecedented healthcare system challenges, some of which will lead to transformative change. It is obvious to healthcare workers and policymakers alike that an effective critical care surge response must be nested within the overall care delivery model. The COVID-19 pandemic has highlighted key elements of emergency preparedness. These include having national or regional strategic reserves of personal protective equipment, intensive care unit (ICU) devices, consumables and pharmaceuticals, as well as effective supply chains and efficient utilization protocols. ICUs must also be prepared to accommodate surges of patients and ICU staffing models should allow for fluctuations in demand. Pre-existing ICU triage and end-of-life care principles should be established, implemented and updated. Daily workflow processes should be restructured to include remote connection with multidisciplinary healthcare workers and frequent communication with relatives. The pandemic has also demonstrated the benefits of digital transformation and the value of remote monitoring technologies, such as wireless monitoring. Finally, the pandemic has highlighted the value of pre-existing epidemiological registries and agile randomized controlled platform trials in generating fast, reliable data. The COVID-19 pandemic is a reminder that besides our duty to care, we are committed to improve. By meeting these challenges today, we will be able to provide better care to future patients.

7.
Nat Immunol ; 22(3): 322-335, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33531712

RESUMO

Immune system dysfunction is paramount in coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in cohorts totaling 208 patients with various stages of disease. MAIT cell frequency is strongly reduced in blood. They display a strong activated and cytotoxic phenotype that is more pronounced in lungs. Blood MAIT cell alterations positively correlate with the activation of other innate cells, proinflammatory cytokines, notably interleukin (IL)-18, and with the severity and mortality of severe acute respiratory syndrome coronavirus 2 infection. We also identified a monocyte/macrophage interferon (IFN)-α-IL-18 cytokine shift and the ability of infected macrophages to induce the cytotoxicity of MAIT cells in an MR1-dependent manner. Together, our results suggest that altered MAIT cell functions due to IFN-α-IL-18 imbalance contribute to disease severity, and their therapeutic manipulation may prevent deleterious inflammation in COVID-19 aggravation.

9.
Proc Natl Acad Sci U S A ; 118(8)2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33536313

RESUMO

The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10-4). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10-3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.


Assuntos
/mortalidade , Modelos Teóricos , Nasofaringe/virologia , RNA Viral/análise , Carga Viral , Idoso , Anticorpos Antivirais/sangue , /epidemiologia , Feminino , França/epidemiologia , Hospitalização , Humanos , Cinética , Masculino , Prognóstico , Estudos Prospectivos , RNA Viral/genética , Fatores de Risco , Taxa de Sobrevida
10.
BMC Cancer ; 21(1): 9, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402107

RESUMO

BACKGROUND: At intensive care unit (ICU) admission, the issue about prognosis of critically ill cancer patients is of clinical interest, especially after ICU discharge. Our objective was to assess the factors associated with 3- and 6-month survival of ICU cancer survivors. METHODS: Based on the French OutcomeRea™ database, we included solid cancer patients discharged alive, between December 2005 and November 2013, from the medical ICU of the university hospital in Grenoble, France. Patient characteristics and outcome at 3 and 6 months following ICU discharge were extracted from available database. RESULTS: Of the 361 cancer patients with unscheduled admissions, 253 (70%) were discharged alive from ICU. The main primary cancer sites were digestive (31%) and thoracic (26%). The 3- and 6-month mortality rates were 33 and 41%, respectively. Factors independently associated with 6-month mortality included ECOG performance status (ECOG-PS) of 3-4 (OR,3.74; 95%CI: 1.67-8.37), metastatic disease (OR,2.56; 95%CI: 1.34-4.90), admission for cancer progression (OR,2.31; 95%CI: 1.14-4.68), SAPS II of 45 to 58 (OR,4.19; 95%CI: 1.76-9.97), and treatment limitation decision at ICU admission (OR,4.00; 95%CI: 1.64-9.77). Interestingly, previous cancer chemotherapy prior to ICU admission was independently associated with lower 3-month mortality (OR, 0.38; 95%CI: 0.19-0.75). Among patients with an ECOG-PS 0-1 at admission, 70% (n = 66) and 61% (n = 57) displayed an ECOG-PS 0-2 at 3- and 6-months, respectively. At 3 months, 74 (55%) patients received anticancer treatment, 13 (8%) were given exclusive palliative care. CONCLUSIONS: Factors associated with 6-month mortality are almost the same as those known to be associated with ICU mortality. We highlight that most patients recovered an ECOG-PS of 0-2 at 3 and 6 months, in particular those with a good ECOG-PS at ICU admission and could benefit from an anticancer treatment following ICU discharge.

11.
Crit Care ; 25(1): 24, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33423691

RESUMO

BACKGROUND: Community-acquired pneumonia (CAP), especially pneumococcal CAP (P-CAP), is associated with a heavy burden of illness as evidenced by high rates of intensive care unit (ICU) admission, mortality, and costs. Although well-defined acutely, determinants influencing long-term burden are less known. This study assessed determinants of 28-day and 1-year mortality and costs among P-CAP patients admitted in ICUs. METHODS: Data regarding all hospital and ICU stays in France in 2014 were extracted from the French healthcare administrative database. All patients admitted in the ICU with a pneumonia diagnosis were included, except those hospitalized for pneumonia within the previous 3 months. The pneumococcal etiology and comorbidities were captured. All hospital stays were included in the cost analysis. Comorbidities and other factors effect on the 28-day and 1-year mortality were assessed using a Cox regression model. Factors associated with increased costs were identified using log-linear regression models. RESULTS: Among 182,858 patients hospitalized for CAP in France for 1 year, 10,587 (5.8%) had a P-CAP, among whom 1665 (15.7%) required ICU admission. The in-hospital mortality reached 22.8% at day 28 and 32.3% at 1 year. The mortality risk increased with age > 54 years, malignancies (hazard ratio (HR) 1.54, 95% CI [1.23-1.94], p = 0.0002), liver diseases (HR 2.08, 95% CI [1.61-2.69], p < 0.0001), and the illness severity at ICU admission. Compared with non-ICU-admitted patients, ICU survivors remained at higher risk of 1-year mortality. Within the following year, 38.2% (516/1350) of the 28-day survivors required at least another hospital stay, mostly for respiratory diseases. The mean cost of the initial stay was €19,008 for all patients and €11,637 for subsequent hospital stays within 1 year. One-year costs were influenced by age (lower in patients > 75 years old, p = 0.008), chronic cardiac (+ 11% [0.02-0.19], p = 0.019), and respiratory diseases (+ 11% [0.03-0.18], p = 0.006). CONCLUSIONS: P-CAP in ICU-admitted patients was associated with a heavy burden of mortality and costs at one year. Older age was associated with both early and 1-year increased mortality. Malignant and chronic liver diseases were associated with increased mortality, whereas chronic cardiac failure and chronic respiratory disease with increased costs. TRIAL REGISTRATION: N/A (study on existing database).

12.
Intensive Care Med ; 47(2): 180-187, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33506379

RESUMO

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.


Assuntos
/complicações , Infecção Hospitalar , Sepse/epidemiologia , Idoso , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Feminino , França/epidemiologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco
13.
Clin Infect Dis ; 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33277646

RESUMO

BACKGROUND: Ultrasound (US) guidance is frequently used in critically ill patients for central venous catheter (CVC) insertion. The effect of US on infectious risk remains controversial and randomized-controlled trials (RCTs) assessed mainly non-infectious complications. This study assessed infectious risk associated with catheters inserted with US guidance versus use of anatomical 'landmarks' (AL). METHODS: We used individual data from three large RCTs for which a prospective, high-quality data collection was performed. Adult patients were recruited in various intensive care units (ICU) in France as soon as they required short-term CVC insertion. We applied marginal Cox models with inverse probability weighting to estimate the effect of US-guided insertion on catheter-related bloodstream infections (CRBSI, primary outcome) and major catheter-related infections (MCRI, secondary outcome).We also evaluated insertion site colonization at catheter removal. RESULTS: Our post hoc analysis included 4636 patients and 5502 catheters inserted in 2088 jugular, 1733 femoral and 1681 subclavian veins, respectively, in 19 ICUs. US was used for 2147 catheter insertions. Among jugular and femoral CVCs and after weighting, we found an association between US and CRBSI (HR 2.21, 95% CI 1.17-4.16, p=0.014) and between US and MCRI (HR 1.55, 95% CI 1.01-2.38, p=0.045). Catheter insertion site colonization at removal was more common in the US-guided group (p=0.0045) among jugular and femoral CVCs in situ for ≤7 days (n=606). CONCLUSIONS: In prospectively collected data in which catheters were not randomized to insertion by US or AL, US guidance was associated with increased risk of infection.

14.
Lancet ; 396(10265): 1804, 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33278930
15.
PLoS One ; 15(12): e0243261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33270790

RESUMO

BACKGROUND: Rapid identification of patients with high suspicion of COVID-19 will become a challenge with the co-circulation of multiple respiratory viruses (RVs). We have identified clinical or biological characteristics to help distinguish SARS-CoV-2 from other RVs. METHODS: We used a prospective cohort including all consecutive patients admitted through the emergency department's (ED) and presenting respiratory symptoms from November 2019 to April 2020. Patients were tested for RV using multiplex polymerase chain reaction (mPCR) and SARS-CoV-2 RT-PCR. RESULTS: 203/508 patients were positive for an RV during the non-SARS-CoV-2 epidemic period (November to February), and 268/596 patients were SARS-CoV-2 positive during the SARS-CoV-2 epidemic (March to April). Younger age, male gender, fever, absence of expectoration and absence of chronic lung disease were statistically associated with SARS-CoV-2 detection. Combining these variables allowed for the distinguishing of SARS-CoV-2 infections with 83, 65, 75 and 76% sensitivity, specificity, PPV and NPV, respectively. CONCLUSION: Patients' characteristics associated with a positive PCR are common between SARS-CoV-2 and other RVs, but a simple discrimination of strong SARS-CoV-2 suspicion with a limited set of clinical features seems possible. Such scoring could be useful but has to be prospectively evaluated and will not eliminate the need for rapid PCR assays.

16.
Crit Care ; 24(1): 694, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33317594

RESUMO

BACKGROUND: Little is known on the association between local signs and intravascular catheter infections. This study aimed to evaluate the association between local signs at removal and catheter-related bloodstream infections (CRBSI), and which clinical conditions may predict CRBSIs if inflammation at insertion site is present. METHODS: We used individual data from four multicenter randomized controlled trials in intensive care units (ICUs) that evaluated various prevention strategies for arterial and central venous catheters. We used multivariate logistic regressions in order to evaluate the association between ≥ 1 local sign, redness, pain, non-purulent discharge and purulent discharge, and CRBSI. Moreover, we assessed the probability for each local sign to observe CRBSI in subgroups of clinically relevant conditions. RESULTS: A total of 6976 patients and 14,590 catheters (101,182 catheter-days) and 114 CRBSI from 25 ICUs with described local signs were included. More than one local sign, redness, pain, non-purulent discharge, and purulent discharge at removal were observed in 1938 (13.3%), 1633 (11.2%), 59 (0.4%), 251 (1.7%), and 102 (0.7%) episodes, respectively. After adjusting on confounders, ≥ 1 local sign, redness, non-purulent discharge, and purulent discharge were associated with CRBSI. The presence of ≥ 1 local sign increased the probability to observe CRBSI in the first 7 days of catheter maintenance (OR 6.30 vs. 2.61 [> 7 catheter-days], pheterogeneity = 0.02). CONCLUSIONS: Local signs were significantly associated with CRBSI in the ICU. In the first 7 days of catheter maintenance, local signs increased the probability to observe CRBSI.

17.
PLoS One ; 15(12): e0243961, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33326457

RESUMO

BACKGROUND: The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated. MATERIAL AND METHODS: A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3-5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects. RESULTS: Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid±stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80-1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids+/-anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%). CONCLUSION: In COVID-19 non-ICU inpatients at the cytokine release phase, corticosteroids with or without anakinra were associated with a 30% decrease of death risk on Day 15.


Assuntos
/tratamento farmacológico , Glucocorticoides/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Metilprednisolona/uso terapêutico , Idoso , Teorema de Bayes , /patologia , Estudos de Casos e Controles , Estudos de Coortes , Comorbidade , Quimioterapia Combinada , Feminino , Humanos , Unidades de Terapia Intensiva , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Índice de Gravidade de Doença
18.
Artigo em Inglês | MEDLINE | ID: mdl-33172592

RESUMO

The 2020 International Web Scientific Event in COVID-19 pandemic in critically ill patients aimed at updating the information and knowledge on the COVID-19 pandemic in the intensive care unit. Experts reviewed the latest literature relating to the COVID-19 pandemic in critically ill patients, such as epidemiology, pathophysiology, phenotypes of infection, COVID-19 as a systematic infection, molecular diagnosis, mechanical ventilation, thromboprophylaxis, COVID-19 associated co-infections, immunotherapy, plasma treatment, catheter-related bloodstream infections, artificial intelligence for COVID-19, and vaccination. Antiviral therapy and co-infections are out of the scope of this review. In this review, each of these issues is discussed with key messages regarding management and further research being presented after a brief review of available evidence.

19.
Intensive Care Med ; 46(12): 2168-2183, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33175277

RESUMO

Pulmonary infection is one of the main complications occurring in patients suffering from acute respiratory distress syndrome (ARDS). Besides traditional risk factors, dysregulation of lung immune defenses and microbiota may play an important role in ARDS patients. Prone positioning does not seem to be associated with a higher risk of pulmonary infection. Although bacteria associated with ventilator-associated pneumonia (VAP) in ARDS patients are similar to those in patients without ARDS, atypical pathogens (Aspergillus, herpes simplex virus and cytomegalovirus) may also be responsible for infection in ARDS patients. Diagnosing pulmonary infection in ARDS patients is challenging, and requires a combination of clinical, biological and microbiological criteria. The role of modern tools (e.g., molecular methods, metagenomic sequencing, etc.) remains to be evaluated in this setting. One of the challenges of antimicrobial treatment is antibiotics diffusion into the lungs. Although targeted delivery of antibiotics using nebulization may be interesting, their place in ARDS patients remains to be explored. The use of extracorporeal membrane oxygenation in the most severe patients is associated with a high rate of infection and raises several challenges, diagnostic issues and pharmacokinetics/pharmacodynamics changes being at the top. Prevention of pulmonary infection is a key issue in ARDS patients, but there is no specific measure for these high-risk patients. Reinforcing preventive measures using bundles seems to be the best option.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33152538

RESUMO

OBJECTIVES: Data on the impact of systemic antibiotics at the time of catheter insertion are scarce. Therefore, we assessed the association between concurrent antibiotic administration at insertion and short-term catheter-related infections. METHODS: We used individual data gathered from five large, randomized, controlled ICU trials. We analysed adult patients who required arterial, short-term central venous or dialysis catheter insertion in the ICU. The effect of antibiotics at insertion on major catheter-related infection (MCRI), catheter-related bloodstream infection (CRBSI) and colonization was estimated using multivariate marginal Cox and propensity score models. RESULTS: We included 10 269 patients and 18 743 catheters from 36 ICUs. Antibiotic use was ongoing at the time of 11 361 catheter insertions (60.6%). After adjusting for well-known risk factors for intravascular catheter infection, we observed a similar risk for MCRI (HR 0.83, 95%CI 0.62-1.10, p 0.19) and CRBSI (HR 0.85, 95%CI 0.60-1.22, p 0.38) between the antibiotic and no-antibiotic groups. A confirmatory analysis using propensity score showed consistent results. No specific antibiotic subclasses reduced the risk of MCRI. Non-fermenting Gram-negative bacilli were more frequently observed in the antibiotic group. CONCLUSIONS: Ongoing antibiotic administration at the time of catheter insertion was not associated with a decrease risk of catheter-related infections and should not be carried out for preventing such infections. Our results bring new insights to antimicrobial stewardship in critically ill patients and may direct empirical antimicrobial therapy if an intravascular catheter infection is suspected.

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