Tocilizumab Association with Emerging Multi-drug Resistance Organisms and Mortality in critically ill patients with Coronavirus disease 2019 (COVID-19): A Multicenter, Retrospective Cohort Study

Abstract Background:Tocilizumab is an IgG1 class recombinant humanized monoclonal antibody that directly inhibits IL-6 receptor. Several randomized clinical trials (RCTs) have evaluated tocilizumab’s safety and efficacy in patients with COVID-19. These studies demonstrated conflicting results regarding tocilizumab’s efficacy and safety. Our study aim is to determine the association between treatment with tocilizumab and emergence of multidrug-resistant bacteria and its effect on mortality in critically ill patients with Coronavirus disease 2019 (COVID-19).Methods:A multicenter, retrospective, cohort study conducted at two governmental tertiary hospitals in Saudi Arabia. All critically ill patients who were admitted to intensive care units (ICUs) with a positive COVID-19 PCR test between March 1st, 2020 and January 31st, 2021 were included. Patients who received tocilizumab were compared to patients who did not receive it. Results:A total of 738 patients met our inclusion criteria and were included in the analysis. Of these 262 (35.5%) received tocilizumab and 476 (64.5%) were included in the control group. Patients who received tocilizumab did not have higher odds for the microbial isolation (OR 1.34; 95% CI, 0.91-1.94 p = 0.13), development of resistant organisms (OR 1.00; 95% CI, 0.51-1.98 p = 0.99), or detection of Carbapenem-Resistant Enterobacteria (CRE) (OR 0.67; 95% CI, 0.29-1.54 p = 0.34). In a multivariable logistic regression adjusting for possible cofounders, there was no difference in 30-day ICU mortality (OR 0.96; 95% CI, 0.65-1.43 p = 0.85) or in-hospital mortality (OR 1.18; 95% CI, 0.79-1.76 p = 0.42). However, there was a significant difference in the incidence of respiratory failure requiring MV between the two groups (OR 2.27; 95% CI, 1.05-4.89 p = 0.03).Conclusions: Tocilizumab use in critically ill COVID-19 patients was not associated with microbial isolation, emergence of resistant organisms, detection of CRE organisms, or mortality benefits. However, tocilizumab use was associated with an increased risk of respiratory failure requiring mechanical ventilation.

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Association between tocilizumab and emerging multidrug-resistant organisms in critically ill patients with COVID-19: A multicenter, retrospective cohort study

BMC Infectious Diseases ◽

10.1186/s12879-021-06813-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ohoud Aljuhani ◽

Khalid Al Sulaiman ◽

Adel Alshabasy ◽

Khalid Eljaaly ◽

Abdulrahman I. Al Shaya ◽

...

Keyword(s):

Cohort Study ◽

Critically Ill ◽

Retrospective Cohort Study ◽

Critically Ill Patients ◽

Retrospective Cohort ◽

Randomized Clinical Trials ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Control Group ◽

Microbial Isolation

Abstract Background Tocilizumab is an IgG1 class recombinant humanized monoclonal antibody that directly inhibits the IL-6 receptor. Several randomized clinical trials have evaluated its safety and efficacy in patients with coronavirus disease 2019 (COVID-19), and these studies demonstrate conflicting results. Our study aimed to determine the association between tocilizumab treatment and microbial isolation and emergence of multidrug-resistant bacteria in critically ill patients with COVID-19. Methods A multicenter retrospective cohort study was conducted at two tertiary government hospitals in Saudi Arabia. All critically ill patients admitted to intensive care units with a positive COVID-19 PCR test between March 1 and December 31, 2020, who met study criteria were included. Patients who received tocilizumab were compared to those who did not receive it. Results A total of 738 patients who met our inclusion criteria were included in the analysis. Of these, 262 (35.5%) received tocilizumab, and 476 (64.5%) were included in the control group. Patients who received tocilizumab had higher odds for microbial isolation (OR 1.34; 95% CI 0.91–1.94, p = 0.13); however, the difference was not statistically significant. Development of resistant organisms (OR 1.00; 95% CI 0.51–1.98, p = 0.99) or detection of carbapenem-resistant Enterobacteriaceae (CRE) (OR 0.67; 95% CI 0.29–1.54, p = 0.34) was not statistically significant between the two groups. Conclusions Tocilizumab use in critically ill patients with COVID-19 is not associated with higher microbial isolation, the emergence of resistant organisms, or the detection of CRE organisms.

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Empiric Therapeutic Anticoagulation and Mortality in Critically Ill Patients With Respiratory Failure From SARS‐CoV‐2: A Retrospective Cohort Study

The Journal of Clinical Pharmacology ◽

10.1002/jcph.1749 ◽

2020 ◽

Vol 60 (11) ◽

pp. 1411-1415

Author(s):

John Ferguson ◽

Stacy Volk ◽

Thomas Vondracek ◽

John Flanigan ◽

Andrew Chernaik

Keyword(s):

Cohort Study ◽

Respiratory Failure ◽

Critically Ill ◽

Retrospective Cohort Study ◽

Critically Ill Patients ◽

Retrospective Cohort ◽

Therapeutic Anticoagulation

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Inflammation Cytokine Expression and Association With Clinical Outcomes in Critically Ill Patients After Major Surgery: A Retrospective Cohort Study

10.21203/rs.3.rs-32628/v1 ◽

2020 ◽

Author(s):

Yamin Yan ◽

Xiaorong Wang ◽

Yan Hu ◽

Zhenghong Yu ◽

Yingjia Tang ◽

...

Keyword(s):

Cohort Study ◽

Mortality Rate ◽

Critically Ill ◽

Patient Outcomes ◽

Retrospective Cohort Study ◽

Critically Ill Patients ◽

Retrospective Cohort ◽

Major Surgery ◽

Increased Risk ◽

Tnf Α

Abstract Background The associations of serum cytokine levels and critically ill patient outcomes after major surgery remain unclear. The use of cytokine markers to predict outcomes in critically ill patients is controversial.Objective To determine the levels of IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α and procalcitonin in critical surgical ICU(SICU) patients and evaluate their associations with patient outcome and clinical significance.Methods This was a retrospective cohort study of consecutive patients admitted to the SICU in Zhongshan Hospital, Fudan University. The program ran from January 1, 2018, to June 30, 2019. The levels of IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α and procalcitonin were detected, and their relationship with patient outcomes was investigated.The primary outcome was in-hospital mortality, compared by a multivariable logistic regression analysis among the survivors and nonsurvivors.Results Overall, 5,257 patients were included in this study for their first SICU admission; 5,099 patients survived, 158 patients died, and the mortality rate was 3.0%(158/5,257). Univariate and multivariate analyses showed that nonsurvivors had increased levels of IL-1(OR=1.855, P=0.000) and IL-2(OR=1.51, P=0.000) compared with survivors. In addition, 196 patients(3.7%) were readmitted to the SICU, and data from 187 patients were collected. Of these, 161 patients survived, and 26 patients died; the mortality rate was 13.9%(26/187), which was much higher than that of the first round of patients. The level of IL-2 significantly influenced SICU readmission(OR=3.921, P=0.000).For the third round of SICU admission, 10 patients were included, 7 patients survived, and 3 patients died; the mortality rate was 30.0%(3/10). Furthermore, older age, longer time of SICU stay, and higher rate of mechanical ventilation and CRRT were associated with patient death.Conclusions High levels of cytokines may be risk factors for mortality and SICU readmission in critically ill patients who receive major surgery. Further work is still needed to determine which unmeasured characteristics and therapies may contribute to the increased risk observed.

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Association between prehospital vitamin D status and incident acute respiratory failure in critically ill patients: a retrospective cohort study

BMJ Open Respiratory Research ◽

10.1136/bmjresp-2014-000074 ◽

2015 ◽

Vol 2 (1) ◽

pp. e000074 ◽

Cited By ~ 34

Author(s):

David R Thickett ◽

Takuhiro Moromizato ◽

Augusto A Litonjua ◽

Karin Amrein ◽

Sadeq A Quraishi ◽

...

Keyword(s):

Vitamin D ◽

Cohort Study ◽

Respiratory Failure ◽

Acute Respiratory Failure ◽

Critically Ill ◽

Retrospective Cohort Study ◽

Critically Ill Patients ◽

Retrospective Cohort ◽

Vitamin D Status

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Time in blood glucose range 70 to 180 mg/dL and survival rate in critically ill patients: A retrospective cohort study

PLoS ONE ◽

10.1371/journal.pone.0252158 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0252158

Author(s):

Hiromu Naraba ◽

Tadahiro Goto ◽

Toru Shirakawa ◽

Tomohiro Sonoo ◽

Naoki Kanda ◽

...

Keyword(s):

Cohort Study ◽

Blood Glucose ◽

Critically Ill ◽

Retrospective Cohort Study ◽

Critically Ill Patients ◽

Retrospective Cohort ◽

Glycosylated Hemoglobin ◽

Tertiary Care ◽

Increased Risk ◽

Blood Glucose Range

Background While time in targeted blood glucose range (TIR) 70–140 mg/dL is a known factor associated with mortality in critically ill patients, it remains unclear whether TIR is associated with 28-day mortality under the glycemic control with a less tight target glucose range of 70–180 mg/dL. We aimed to examine whether TIR 70–180 mg/dL was associated with 28-day mortality. Methods This is a retrospective cohort study using data from a tertiary care center in Japan collected from January 2016 through October 2019. We included adult patients (aged ≥20 years) admitted to the ICU. We excluded patients 1) with diabetic ketoacidosis patients, 2) discharged within 48 hours, 3) with repeated ICU admissions. We calculated TIR 70–180 mg/dL using the measured blood glucose values (≥3 times per day). The primary outcome was 28-day mortality. We examined the association between TIR and 28-day mortality using a logistic regression and Cox proportional hazard models with a stratification by glycosylated hemoglobin (HbA1c) level of 6.5%. Additionally, we repeated the analyses using the TIR category to assess the optimal TIR. For the sensitivity analysis, we repeated the primary analysis using TIR during the first three days from ICU admission. Results Of 1,230 patients, the median age was 72 years, 65% were male, and 250 patients (20%) had HbA1c ≥6.5% on admission. In patients with HbA1c <6.5%, TIR <80% was associated with an increased risk of 28-day mortality, with an adjusted odds ratio (OR) of 1.88 (95%CI: 1.36–2.61). Likewise, when using 10% incremental TIR as a categorical variable, lower TIR was associated with a worse 28-day mortality compared with TIR ≥90% (e.g., adjusted OR of TIR <60%, 3.62 [95%CI 2.36–5.53]). Similar associations were found in the analyses using Cox proportional hazards model and using TIR during the first three days. By contrast, in patients with HbA1c ≥6.5%, there was no consistent association of TIR with 28-day mortality. Conclusions We found that lower TIR 70–180 mg/dL was associated with a higher 28-day mortality in critically ill patients with HbA1c <6.5%, whereas there was no consistent association in patients with HbA1c ≥6.5%.

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The associations between cytokine levels and clinical outcomes in critically ill patients after surgery: a retrospective cohort study

10.21203/rs.3.rs-23942/v1 ◽

2020 ◽

Author(s):

Yamin Yan ◽

Xiaorong Wang ◽

Yan Hu ◽

Zhenghong Yu ◽

Yingjia Tang ◽

...

Keyword(s):

Cohort Study ◽

Mortality Rate ◽

Critically Ill ◽

Patient Outcomes ◽

Retrospective Cohort Study ◽

Critically Ill Patients ◽

Retrospective Cohort ◽

Increased Risk ◽

Tnf Α ◽

Cytokine Levels

Abstract Background The associations of serum cytokine levels and critically ill patient outcomes after surgery remain unclear. The use of cytokine markers to predict outcomes in critically ill patients is controversial. Objective To determine the levels of IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α and procalcitonin in critical surgical ICU (SICU) patients and evaluate their associations with patient outcome and clinical significance. Methods This was a retrospective cohort study of consecutive patients admitted to the SICU in Zhongshan Hospital, Fudan University. The program ran from January 1, 2018, to June 30, 2019. The levels of IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α and procalcitonin were detected, and their relationship with patient outcomes was investigated. The primary outcome was in-hospital mortality, compared by a multivariable logistic regression analysis among the survivors and nonsurvivors. Results Overall, 5,257 patients were included in this study for their first SICU admission; 5,099 patients survived, 158 patients died, and the mortality rate was 3.0% (158/5,257). Univariate and multivariate analyses showed that nonsurvivors had increased levels of IL-1β (OR = 1.855, P = 0.000) and IL-2 (OR = 1.51, P = 0.000) compared with survivors. In addition, 196 patients (3.7%) were readmitted to the SICU, and data from 187 patients were collected. Of these, 161 patients survived, and 26 patients died; the mortality rate was 13.9% (26/187), which was much higher than that of the first round of patients. The level of IL-2 significantly influenced SICU readmission (OR = 3.921, P = 0.000). For the third round of SICU admission, 10 patients were included, 7 patients survived, and 3 patients died; the mortality rate was 30.0% (3/10). Furthermore, older age, longer time of SICU stay, and higher rate of mechanical ventilation and CRRT were associated with patient death. Conclusions High levels of cytokines may be risk factors for mortality and SICU readmission in critically ill patients who receive surgery. Further work is still needed to determine which unmeasured characteristics and therapies may contribute to the increased risk observed.

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Proton pump inhibitors versus histamine-2 receptor blockers for stress ulcer prophylaxis in patients with sepsis: a retrospective cohort study

Journal of International Medical Research ◽

10.1177/03000605211025130 ◽

2021 ◽

Vol 49 (6) ◽

pp. 030006052110251

Author(s):

Minqiang Huang ◽

Ming Han ◽

Wei Han ◽

Lei Kuang

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Hospital Mortality ◽

Critically Ill ◽

Proton Pump ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Stress Ulcer ◽

Increased Risk ◽

Ulcer Prophylaxis

Objective We aimed to compare the efficacy and risks of proton pump inhibitor (PPI) versus histamine-2 receptor blocker (H2B) use for stress ulcer prophylaxis (SUP) in critically ill patients with sepsis and risk factors for gastrointestinal bleeding (GIB). Methods In this retrospective cohort study, we used the Medical Information Mart for Intensive Care III Clinical Database to identify critically ill adult patients with sepsis who had at least one risk factor for GIB and received either an H2B or PPI for ≥48 hours. Propensity score matching (PSM) was conducted to balance baseline characteristics. The primary outcome was in-hospital mortality. Results After 1:1 PSM, 1056 patients were included in the H2B and PPI groups. The PPI group had higher in-hospital mortality (23.8% vs. 17.5%), GIB (8.9% vs. 1.6%), and pneumonia (49.6% vs. 41.6%) rates than the H2B group. After adjusting for risk factors of GIB and pneumonia, PPI use was associated with a 1.28-times increased risk of in-hospital mortality, 5.89-times increased risk of GIB, and 1.32-times increased risk of pneumonia. Conclusions Among critically ill adult patients with sepsis at risk for GIB, SUP with PPIs was associated with higher in-hospital mortality and higher risk of GIB and pneumonia than H2Bs.

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