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

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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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

10.21203/rs.3.rs-469073/v1 ◽

2021 ◽

Author(s):

Ohoud Aljuhani ◽

Khalid Al Sulaiman ◽

Adel Alshabasy ◽

Khalid Eljaaly ◽

Abdulrahman I. Al Shaya ◽

...

Keyword(s):

Cohort Study ◽

Respiratory Failure ◽

Critically Ill ◽

Retrospective Cohort Study ◽

Critically Ill Patients ◽

Retrospective Cohort ◽

Resistant Bacteria ◽

Microbial Isolation ◽

Increased Risk ◽

Significant Difference

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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