Low-dose tocilizumab is associated with improved outcome and a low risk of secondary infection in severe COVID-19 pneumonia

Background Respiratory failure and death are the leading causes of severe Coronavirus disease 2019 (COVID-19). Hyper-inflammation and cytokine storm cause lung damage. This study aimed to compare the low-dose and high-dose effects of tocilizumab, an IL-6 receptor antagonist. Method Patients with severe pneumonia and hyper-inflammation signs because of COVID-19 were included in this retrospective study. Patients receiving tocilizumab = 200 mg as the high-dose group, and those not treated with tocilizumab as the control group. Demographic and clinical data of patients who died and survived in both low-high dose and control patients were compared. According to symptom day and radiological infiltration, patients with tocilizumab were also evaluated in two groups as early and late periods at tocilizumab administration time. Results A total of 160 patients were included in the study; 70 were treated with a low dose and 50 with high-dose tocilizumab. Forty patients were in the control group. Age, comorbidity and clinical features were similar in the control, low-dose tocilizumab and high-dose tocilizumab groups. The mortality rate (12.9%, 30.0%, 37.5, P = .008) was less in the low-dose tocilizumab group. The secondary infection rate was higher in the high-dose group than in the low-dose tocilizumab and control groups (44.0%, 10.0%, 10.0%, P < .001). Distinguishing between those patients who died and survived, age (OR: 1.1589, P < .001), higher APACHE II scores (OR: 1.225, P = .001) and needs for non-invasive mechanical ventilation (OR: 14.469, P < .001) were the most critical risk factors. Low-dose tocilizumab was associated with a lower mortality rate (OR: 0.244, P = .012). Conclusion The use of tocilizumab at a low dose is associated with lower secondary infections and mortality

The Effects of Dexmedetomidine on Secondary Acute Lung and Kidney Injuries in the Rat Model of Intra-Abdominal Sepsis

In the present study, the effects of dexmedetomidine on secondary lung and kidney injuries were studied in the rat model of intra-abdominal sepsis by immunohistological and biochemical examinations. We measured serum creatinine, kidney tissue malondialdehide and plasma neutrophil gelatinase-associated lipocalin levels. In order to evaluate tissue injury we determined kidney tissue mononuclear cell infiltration score, alveolar macrophage count, histological kidney and lung injury scores and kidney and lung tissue immunoreactivity scores. We demonstrated that dexmedetomidine attenuates sepsis-induced lung and kidney injuries and apoptosis in the rat model of sepsis. There is still need for comparative studies in order to determine the effects of dexmedetomidine on organ functions in early human sepsis

Ischemic preconditioning attenuates lipid peroxidation and apoptosis in the cecal ligation and puncture model of sepsis

Sepsis and septic shock are are among the major causes of mortality in intensive care units. The lung and kidney are the organs most affected by sepsis. Evidence exists that lipid peroxidation and apoptosis may be responsible for the high mortality due to sepsis. Ischemic preconditioning (IP) is a method for the protection of tissues and organs against ischemia/reperfusion injury by reducing reactive oxygen species levels, lipid peroxidation and apoptosis. In the present study, the effects of IP were investigated in cecal ligation and puncture (CLP)-induced sepsis in rats. The three groups of animals used in the present controlled study were the sham-operated group (sham, n=7), which only underwent a laparotomy; the sepsis group (sepsis, n=7), which underwent cecal ligation and perforation; and the IP + sepsis group (IP+sepsis, n=7), which underwent CLP immediately prior to the application of three cycles of IP to the hind limb. The study was terminated at 6 h after the induction of CLP. Blood, kidney and lung tissue samples were collected for the determination of serum creatinine, blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL) and lung tissue malondialdehyde (MDA) levels, as well as histological examination. The serum creatinine, plasma NGAL and lung tissue MDA levels in the sepsis group were significantly increased compared with those in the sham and the IP+sepsis groups (P<0.05). Alveolar macrophage counts, histological kidney and lung injury scores, kidney (caspase 3) and lung tissue immuonreactivity (M30) scores in the sepsis group were also significantly increased compared with those in the sham and IP+sepsis groups (P<0.05). The alveolar macrophage count in the IP+sepsis group was increased compared with that in the sham group (P<0.05). In conclusion, IP inhibits lipid peroxidation and attenuates histological injury and apoptosis in the lung and kidney during sepsis

Outcomes of High-Dose Vitamin C Therapy on Patients Diagnosed with COVID-19 Associated ARDS in Intensive Care Units: Multi-Center Retrospective Study

Background and Aim: The new type of Severe Acute Respiratory Syndrome Coronavirus 2 (Coronavirus 2019-COVID-19) infection is the largest pandemic in the last decade. Acute respiratory distress syndrome is the complication with the highest mortality rate of this infection and there is no adequate treatment with proven efficacy to reduce mortality. This multi-center, retrospective study aimed to determine the effect of high-dose vitamin C on survival and other endpoints in invasively ventilated ARDS patients.Methods: This multi-center, observational retrospective cohort study was performed at five ICU centers between March 2020 and July 2020. Patients with ARDS due to COVID-19 who required IMV were included. High-dose vitamin C group was defined as patients who were treated with vitamin C over 200 mg/kg for four days. Patients who were not given vitamin C treatment were defined as the control group by using propensity score match analysis, as well. The groups were compared about the effects of high-dose vitamin C treatment on ICU mortality.Result: A total of 86 patients with a mean age of 67.85 +/- 10.38 were included in the study. 72.1% of the patients were male. Forty-two (49%) patients were in the high dose vitamin C group, and 44 (51%) were in the control group. The mean PaO2/FiO2 at the time of admission to the ICU was 128.27 +/- 58.69 mmHg (133.63 +/- 56.51 mmHg in the control group, 122.36 +/- 61.18 mmHg in the study group, p=0.389). The mortality rate of high dose vitamin C group was lower than the control group (73.8% vs. 90.9%, p = 0.037,respectively).Conclusion: As an adjunctive therapy in invasively ventilated patients with COVID-19-associated ARDS, high doses of vitamin C may reduce mortality and development of organ damage. Prospective, randomized controlled studies with larger numbers of patients are needed to confirm these findings

Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study

Funder: European society of Intensive Care MedicineFunder: European Society of Clinical Microbiology and Infectious Diseases (ESCMID)Funder: Norva Dahlia foundation and the Redcliffe Hospital Private Practice Trust FundAbstract Background The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. Methods We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients’ characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. Results A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p &lt; 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49–2.45). Conclusions We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245. Registered 3 May 2019. </jats:sec

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections

Purpose: The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI). Methods: We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24&nbsp;h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators. Results: Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality. Conclusion: Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients

Presentation, management, and outcomes of older compared to younger adults with hospital-acquired bloodstream infections in the intensive care unit: a multicenter cohort study

Purpose: Older adults admitted to the intensive care unit (ICU) usually have fair baseline functional capacity, yet their age and frailty may compromise their management. We compared the characteristics and management of older (≥ 75&nbsp;years) versus younger adults hospitalized in ICU with hospital-acquired bloodstream infection (HA-BSI). Methods: Nested cohort study within the EUROBACT-2 database, a multinational prospective cohort study including adults (≥ 18&nbsp;years) hospitalized in the ICU during 2019-2021. We compared older versus younger adults in terms of infection characteristics (clinical signs and symptoms, source, and microbiological data), management (imaging, source control, antimicrobial therapy), and outcomes (28-day mortality and hospital discharge). Results: Among 2111 individuals hospitalized in 219 ICUs with HA-BSI, 563 (27%) were ≥ 75&nbsp;years old. Compared to younger patients, these individuals had higher comorbidity score and lower functional capacity; presented more often with a pulmonary, urinary, or unknown HA-BSI source; and had lower heart rate, blood pressure and temperature at presentation. Pathogens and resistance rates were similar in both groups. Differences in management included mainly lower rates of effective source control achievement among aged individuals. Older adults also had significantly higher day-28 mortality (50% versus 34%, p &lt; 0.001), and lower rates of discharge from hospital (12% versus 20%, p &lt; 0.001) by this time. Conclusions: Older adults with HA-BSI hospitalized in ICU have different baseline characteristics and source of infection compared to younger patients. Management of older adults differs mainly by lower probability to achieve source control. This should be targeted to improve outcomes among older ICU patients

Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study

Purpose In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. Methods We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. Results 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28. Conclusions HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes