Impact of extended-spectrum β-lactamases and carbapenem-resistant Gram-negative infections on sepsis mortality at the emergency department: a cohort study

Sabino, Scolletta; Monroy, H.M Zaldivar; Jara, Carlos; López, Oscar Álvarez; Ramos, Fabiano; Falci, Diego Rodrigues; Rigatto, Maria Helena

doi:10.1016/j.jhin.2018.05.009

Cited by 4 publications

(2 citation statements)

References 6 publications

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“…Median time from hospital admission to sepsis diagnosis for CRE-infected patients was significantly higher than for patients with infections caused by other bacteria: 12 (IQR, 3.5 to 31) days versus 1 (IQR, 0 to 9.7) day, respectively ( P < 0.01). A detailed description of patients with carbapenem-resistant infections with onset within the first 48 h of hospital admission is given elsewhere (6).…”

Section: Resultsmentioning

confidence: 99%

A Cohort Study of the Impact of Carbapenem-Resistant Enterobacteriaceae Infections on Mortality of Patients Presenting with Sepsis

Sabino

Soares

Ramos

et al. 2019

mSphere

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The objective of this study is to evaluate the impact of carbapenem-resistant Enterobacteriaceae (CRE) infection on sepsis 30-day mortality. A retrospective cohort of patients >18 years old with sepsis and organ dysfunction or septic shock was conducted. Univariate analysis was done for variables potentially related to 30-day mortality, and the ones with P values of <0.05 were included in a backward stepwise hierarchic Cox regression model. Variables that remained with P values of <0.05 were retained in the model. A total of 1,190 sepsis episodes were analyzed. Gram-negative bacterial infections occurred in 391 (68.5%) of 571 patients with positive cultures, of which 69 (17.7%) were caused by a CRE organism. Patients with CRE infections had significantly higher 30-day mortality: 63.8% versus 33.4% (P < 0.01). CRE infection was also associated with a lower rate of appropriate empirical therapy (P < 0.01) and with the presence of septic shock (P < 0.01). In the hierarchic multivariate model, CRE remained significant when controlling for demographic variables, comorbidities, and infection site but lost significance when controlling for septic shock and appropriate empirical therapy. Older age (P < 0.01), HIV-positive status (P < 0.01), cirrhosis (P < 0.01), septic shock (P < 0.01), higher quick sepsis-related organ failure assessment (quick-SOFA) (P < 0.01), and appropriate empirical therapy (P = 0.01) remained in the final model. CRE infections were associated with higher crude mortality rates. A lower rate of appropriate empirical therapy and late diagnosis were more frequent in this group, and improvement of stewardship programs is needed. IMPORTANCE The importance of this work relies on exploring the impact of multidrug-resistant bacterial infections such as those with carbapenem-resistant Enterobacteriaceae (CRE) on sepsis mortality. These infections are growing at alarming rates worldwide and are now among the most frequent and difficult-to-treat bacteria due to the very few options for susceptible antimicrobials available. This study examined 1,190 sepsis episodes, and the main findings were as follows: (i) the prevalence of CRE infections significantly increased over time, (ii) CRE infection was associated with higher 30-day mortality than that of patients with other infections (63.8% versus 33.4%), and (iii) the effect of CRE on mortality was probably influenced by the fact that those patients received lower rates of empirical therapy with active antibiotics and were also diagnosed in more advanced stages of sepsis (septic shock). Those findings point to the need for rapid diagnostic methods to identify these bacteria and the need to adjust therapeutic guidelines to this worrisome epidemiological scenario.

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Section: Resultsmentioning

confidence: 99%

A Cohort Study of the Impact of Carbapenem-Resistant Enterobacteriaceae Infections on Mortality of Patients Presenting with Sepsis

Sabino

Soares

Ramos

et al. 2019

mSphere

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“…Accumulating evidence has indicated that sepsis induces a type of myopathy characterized by a diminished muscle force-generating capacity, atrophy (loss of muscle mass), and altered bioenergetics (3,10). Despite of laborious efforts for searching the treatment for sepsis, the number of patients who died of sepsis reached 30% each month after having being diagnosed (16). Therefore, it is necessary to better understand the cellular mechanisms and pathophysiology associated with sepsis, whereby the potential biochemical alterations in the host tissues infected with sepsis and the formulation of appropriate treatment should be paid attention to (20).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-140 inhibits skeletal muscle glycolysis and atrophy in endotoxin-induced sepsis in mice via the WNT signaling pathway

Liu

et al. 2019

American Journal of Physiology-Cell Physiology

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Sepsis is a systemic inflammatory response syndrome resulting from infection. This study aimed at exploring the role of microRNA-140 (miR-140) in septic mice. Wnt family member 11 (WNT11) was verified to be a target gene of miR-140 after bioinformatic prediction and dual luciferase reporter gene assay. Importantly, miR-140 negatively regulated WNT11. We initially induced the model of sepsis by endotoxin, and then ectopic expression and knockdown experiments were performed to explore the functional role of miR-140 in sepsis. Additionally, cross-sectional areas of muscle fiber, lactic acid production, 3-methylhistidine (3-MH) and tyrosine (Tyr) production in extensor digitorium longus (EDL) muscles, and serum levels of inflammatory factors were examined. The effect of miR-140 on the expression of WNT signaling pathway-related and apoptosis-related factors in skeletal muscle tissue was determined. The experimental results indicated that upregulated miR-140 or silenced WNT11 increased cross-sectional areas of muscle fiber while decreasing lactic acid production, skeletal muscle cell apoptosis [corresponding to downregulated B cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3 and upregulated Bcl-2], and the proteolytic rate of Tyr and 3-MH. Also, overexpressed miR-140 or silenced WNT11 reduced inflammation as reflected by decreased serum levels of IL-6, IL-10, and TNF-α. Furthermore, overexpression of miR-140 was shown to suppress the activation of the WNT signaling pathway, accompanied by decreased expression of WNT11, β-catenin, and GSK-3β. Taken together, upregulation of miR-140 could potentially inhibit skeletal muscle lactate release, an indirect measure of glycolysis, and atrophy in septic mice through suppressing the WNT signaling pathway via inhibiting WNT11 expression.

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Oxygenating the argument for consistent performance of anaerobic blood cultures and blood volumes collected

Weinbren

Weston

Woods

et al. 2019

Journal of Hospital Infection

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Impact of extended-spectrum β-lactamases and carbapenem-resistant Gram-negative infections on sepsis mortality at the emergency department: a cohort study

Cited by 4 publications

References 6 publications

A Cohort Study of the Impact of Carbapenem-Resistant Enterobacteriaceae Infections on Mortality of Patients Presenting with Sepsis

A Cohort Study of the Impact of Carbapenem-Resistant Enterobacteriaceae Infections on Mortality of Patients Presenting with Sepsis

MicroRNA-140 inhibits skeletal muscle glycolysis and atrophy in endotoxin-induced sepsis in mice via the WNT signaling pathway

Oxygenating the argument for consistent performance of anaerobic blood cultures and blood volumes collected

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