Clasificación de riesgo y tiempo puerta-antibiótico en pacientes con sospecha de sepsis / Risk classification and door-to-antibiotic time in patients with suspected sepsis / Classificação de risco e tempo porta-antibiótico no paciente com suspeita de sepse

Objetivo: evaluar la asociación entre la clasificación de riesgo y el tiempo puerta-antibiótico en pacientes con sospecha de sepsis. Método: estudio de cohorte retrospectivo, con una muestra de 232 pacientes con sospecha de sepsis atendidos en el departamento de emergencias. Se dividieron en 2 grupos: con y sin clasificación de riesgo. Una vez identificado el tiempo puerta-antibiótico, se realizó un análisis de varianza de un factor con la prueba post hoc de Bonferroni o la prueba t de Student independiente para variables cuantitativas continuas; pruebas de correlación de Pearson, correlación biserial puntual o correlación biserial para análisis de asociación; y procedimiento de bootstrap cuando no había distribución normal de variables. Para el análisis de los datos se utilizó el software Statistical Package for the Social Sciences. Resultados: el tiempo puerta-antibiótico no difirió entre el grupo que recibió clasificación de riesgo en comparación con el que no fue clasificado. El tiempo puerta-antibiótico fue significativamente más corto en el grupo que recibió una clasificación de riesgo de alta prioridad. Conclusión: no hubo asociación entre el tiempo puerta-antibiótico y si se realizó o no la clasificación de riesgo, ni con la hospitalización en enfermería y en unidad de cuidados intensivos, ni con la duración de la estancia hospitalaria. Se observó que cuanto mayor era la prioridad, más corto era el tiempo puerta-antibiótico.

Objective: to evaluate the association between risk classification and door-to-antibiotic time in patients with suspected sepsis. Method: retrospective cohort study, with a sample of 232 patients with suspected sepsis treated at the emergency department. They were divided into 2 groups: with and without risk classification. Once the door-to-antibiotic time was identified, one-way analysis of variance was performed with Bonferroni post hoc test or independent Student's t-test for continuous quantitative variables; Pearson correlation tests, point-biserial correlation or biserial correlation for association analyses; and bootstrap procedure when there was no normal distribution of variables. For data analysis, the Statistical Package for the Social Sciences software was used. Results: the door-to-antibiotic time did not differ between the group that received risk classification compared to the one that was not classified. Door-to-antibiotic time was significantly shorter in the group that received a high priority risk classification. Conclusion: there was no association between door-to-antibiotic time and whether or not the risk classification was performed, nor with hospitalization in infirmaries and intensive care units, or with the length of hospital stay. It was observed that the higher the priority, the shorter the door-to-antibiotic time.

Objetivo: avaliar a associação entre a realização de classificação de risco e o tempo porta-antibiótico no paciente com suspeita de sepse. Método: estudo de coorte retrospectivo, com amostra de 232 pacientes com suspeita de sepse atendidos no pronto atendimento. Foram distribuídos em 2 grupos: com e sem classificação de risco. Identificado o tempo porta-antibiótico, realizou-se análise de variância de um fator com post hoc de Bonferroni ou teste T-Student independente para variáveis quantitativas contínuas; testes de correlação de Pearson, correlação bisserial por pontos ou correlação bisserial para análises de associação; e procedimento de bootstrap quando não havia distribuição normal de variáveis. Para a análise dos dados foi utilizado o software Statistical Package for the Social Sciences. Resultados: o tempo porta-antibiótico não diferiu entre o grupo que recebeu classificação de risco comparado ao que não foi classificado. O tempo porta-antibiótico foi significativamente menor no grupo que recebeu classificação de risco de alta prioridade. Conclusão: não houve associação entre o tempo porta-antibiótico e a realização ou não da classificação de risco, tampouco com internação em enfermaria e em unidade de terapia intensiva, ou com o tempo de internação hospitalar. Observou-se que quanto maior a prioridade, menor o tempo porta-antibiótico.

Pharmacokinetics and pharmacodynamics of antibiotics in septic children treated with extracorporeal membrane oxygenation / 中华儿科杂志

Objective: To investigate the characteristics of pharmacokinetic (PK) and pharmacodynamic (PD) parameters of antibacterial agents in children with sepsis treated by extracorporeal membrane oxygenation (ECMO). Methods: In this prospective cohort study, 20 children with sepsis (confirmed or suspected) who were treated with ECMO and antimicrobial in the Department of Critical Medicine of Hunan Children's Hospital from March 2021 to December 2022 were enrolled as the ECMO group. Through therapeutic drug monitoring (TDM), the PK-PD parameters of antibacterial agents were analyzed. Twenty five children with sepsis in the same department who were treated with vancomycin but no ECMO at the same time were enrolled as the control group. The individual PK parameters of vancomycin were calculated by Bayesian feedback method. The PK parameters in the two groups were compared, and the correlation between trough concentration and area under the curve (AUC) was analyzed. Wilcoxon rank sum test was used for inter group comparison. Results: Twenty patients in the ECMO group, included 6 males and 14 females, with an onset age of 47 (9, 76) months. In the ECMO group, 12 children (60%) were treated with vancomycin, and the trough concentration was less than 10 mg/L in 7 cases, 10-20 mg/L in 3 cases, and >20 mg/L in 2 cases; AUC/minimum inhibitory concentration (MIC) (MIC=1 mg/L)<400 was in 1 case, 400-600 in 3 cases, and >600 in 8 cases. Among the 11 children (55%) who were treated with β-lactam antibiotics, there were 10 cases with drug concentration at 50% dosing interval (CT50)>4 MIC and 9 cases with trough concentration>MIC, both CT50 and trough concentration of cefoperazone reached the target. Among the 25 cases of control group, 16 were males and 9 females, with an onset age of 12 (8, 32) months. There was a positive correlation between vancomycin trough concentration and AUC (r2=0.36, P<0.001). The half-life of vancomycin and the 24-hour AUC (AUC0-24 h) in the ECMO group were higher than those in the control group (5.3 (3.6, 6.8) vs. 1.9 (1.5, 2.9) h, and 685 (505, 1 227) vs. 261 (210, 355) mg·h/L, Z=2.99, 3.50, respectively; both P<0.05), and the elimination rate constant and clearance rate was lower than those in the control group (0.1 (0.1, 0.2) vs. 0.4 (0.2, 0.5), 0.7 (0.5, 1.3) vs. 2.0 (1.1, 2.8) L/h, Z=2.99, 2.11, respectively; both P<0.05). Conclusion: The PK-PD parameters in septic children treated by ECMO varied with a longer half-life, higher AUC0-24 h, lower elimination rate constant and clearance rate.

Research of progress of mitochondria in the pathogenesis of sepsis / 中华危重病急救医学

Sepsis is an organ dysfunction caused by dysregulation of the body's response to infection, with high morbidity and mortality. The pathogenesis of sepsis is still unclear, and there are no specific treatment drugs. As a cell energy supply unit, the dynamic changes of mitochondria are closely related to various diseases. Studies have shown that structure and function of mitochondria are changed in different organs during sepsis. The energy shortage, oxidative stress change, imbalance of fusion and fission, autophagy reduce, biological functions of mitochondria play important roles in sepsis progress, which can provide a research target for the treatment of sepsis.

Ozonated triglyceride protects against septic lethality via preventing the activation of NLRP3 inflammasome / 中南大学学报(医学版)

OBJECTIVES@#Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to protect infection and inflammation-related diseases due to its role in antibiotic and immunoregulatory effect. Ozonated triglyceride is a key component of ozonated oil that is one of ozone therapy dosage form. However, the potential role of ozonated triglyceride in sepsis remains unclear. This study aims to explore the effect of ozonated triglyceride on septic mouse model and the molecular mechanism.@*METHODS@#Intraperitoneal injection of lipopolysaccharide (LPS), cecal ligation and puncture (CLP) were applied to construct septic mouse model. The mouse serum was obtained for detection of cytokines, and lung tissues were collected for hematoxylin and eosin (HE) staining to evaluate the extent of lung injury in septic mouse with ozonated triglyceride treatment at different time and doses. The survival of septic mice was observed for 96 h and Kaplan-Meier analysis was used to analyze the survival rates. In addition, primary peritoneal macrophages and human acute monocytic-leukemia cell line (THP-1) were treated with inflammasome activators with or without ozonated triglyceride. The level of cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The cleavage of caspase-1 and gasdermin-D (GSDMD) was detected by Western blotting.@*RESULTS@#Ozonated triglyceride at different time and doses reduced the release of inflammasome-related cytokines [interleukin (IL)-1β and IL-18] (all P<0.05) but not pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-α (TNF-α) in septic mice (all P>0.05). Ozonated triglyceride significantly improved the survival rate of septic mice and reduced sepsis-induced lung injury (all P<0.05). Ozonated triglyceride significantly suppressed the canonical and non-canonical activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome (all P<0.05) but not affected absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes in vitro (all P>0.05). Ozonated triglyceride reduced the cleavage of caspase-1 and the downstream GSDMD.@*CONCLUSIONS@#Ozonated triglyceride presents a protect effect on sepsis lethality via reducing cytokines release and sepsis-related organ injury. The mechanism is that ozonated triglyceride specifically suppresses the activation of NLRP3 inflammasome. Ozonated triglyceride is a promising candidate for sepsis treatment.

Overview of systematic reviews of Chinese herbal injections for sepsis / 中国中药杂志

In this study, an overview of systematic reviews/Meta-analysis(SR/MA) of Chinese herbal injections for sepsis was performed to provide references for clinical practice and promote the quality improvement of clinical evidence. Eight Chinese and English databases such as CNKI, Medline, and EMbase were electronically searched for SR/MA of Chinese herbal injections for sepsis from database inception to June 2022. AMSTAR 2, PRISMA 2020, and GRADE system, combined with Recommendations for Clinical Evidence Grading on Traditional Chinese Medicine Based on Evidence Body, were applied to evaluate the methodological quality, reporting quality, and evidence quality of the included articles. Twenty-seven articles of SR/MA were included, containing four Chinese herbal injections(Xuebijing Injection, Shenfu Injection, Shenmai Injection, and Shengmai Injection). AMSTAR 2 checklist showed that the methodological quality of the SR/MA ranged from moderate to very low. Item 2(prior study design) was the critical item with poor scores, and the non-critical items with poor scores were items 3(explain the selection of the study designs), items 10(report on the sources of funding), and items 16(conflicts of interest stated). In terms of PRISMA 2020, items in eight topics with complete reporting of missing>50%, including search strategy, certainty assessment, results of syntheses, certainty of evidence, registration and protocol, support, competing interests, availability of data, code and other materials. The included SR/MA involved 30 outcome indicators. Evidence quality of mortality, APACHE Ⅱ, and safety, the top three outcome indicators, was evaluated, and all of them were graded as the medium level. The lack of random allocation sequence, allocation concealment mechanism, blinding, and trial sample size was the main reason for the reduction of the evidence level. The available evidence shows that Chinese herbal injections can serve as an effective and safe adjunctive treatment for sepsis, which can reduce mortality, inhibit inflammation, improve coagulation function, and regulate immune function, tissue perfusion, and oxygenation in patients with sepsis. However, the quality of SR/MA was suboptimal, and more high-quality SR/MA is needed to provide evidence to support the efficacy and safety of Chinese herbal injections in the treatment of sepsis.

Exploring the treatment of sepsis-associated acute lung injury with Liangge Powder via ERK1/2 and PI3K/AKT pathways: based on network pharmacology and whole animal experimentation / 中华劳动卫生职业病杂志

Objective: To investigate the therapeutic effect and mechanism of Liangge Powder against sepsis-induced acute lung injury (ALI) . Methods: From April to December 2021, the key components of Liangge Powder and its targets against sepsis-induced ALI were analyzed by network pharmacology, and to enrich for relevant signaling pathways. A total of 90 male Sprague-Dawley rats were randomly assigned to sham-operated group, sepsis-induced ALI model group (model group), Liangge Powder low, medium and high dose group, ten rats in the sham-operated group and 20 rats in each of the remaining four groups. Sepsis-induced ALI model was established by cecal ligation and puncture. Sham-operated group: gavage with 2 ml saline and no surgical treatment. Model group: surgery was performed and 2 ml saline was gavaged. Liangge Powder low, medium and high dose groups: surgery and gavage of Liangge Powder 3.9, 7.8 and 15.6 g/kg, respectively. To measure the wet/dry mass ratio of rats lung tissue and evaluate the permeability of alveolar capillary barrier. Lung tissue were stained with hematoxylin and eosin for histomorphological analysis. The levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6 and IL-1β in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The relative protein expression levels of p-phosphatidylinositol 3-kinase (PI3K), p-protein kinase B (AKT), and p-ertracellular regulated protein kinases (ERK) were detected via Western blot analysis. Results: Network pharmacology analysis indicated that 177 active compounds of Liangge Powder were selected. A total of 88 potential targets of Liangge Powder on sepsis-induced ALI were identified. 354 GO terms of Liangge Powder on sepsis-induced ALI and 108 pathways were identified using GO and KEGG analysis. PI3K/AKT signaling pathway was recognized to play an important role for Liangge Powder against sepsis-induced ALI. Compared with the sham-operated group, the lung tissue wet/dry weight ratio of rats in the model group (6.35±0.95) was increased (P<0.001). HE staining showed the destruction of normal structure of lung tissue. The levels of IL-6 [ (392.36±66.83) pg/ml], IL-1β [ (137.11±26.83) pg/ml] and TNF-α [ (238.34±59.36) pg/ml] were increased in the BALF (P<0.001, =0.001, <0.001), and the expression levels of p-PI3K, p-AKT and p-ERK1/2 proteins (1.04±0.15, 0.51±0.04, 2.31±0.41) were increased in lung tissue (P=0.002, 0.003, 0.005). The lung histopathological changes were reduced in each dose group of Liangge Powder compared with the model group. Compared with the model group, the wet/dry weight ratio of lung tissue (4.29±1.26) was reduced in the Liangge Powder medium dose group (P=0.019). TNF-α level [ (147.85±39.05) pg/ml] was reduced (P=0.022), and the relative protein expression levels of p-PI3K (0.37±0.18) and p-ERK1/2 (1.36±0.07) were reduced (P=0.008, 0.017). The wet/dry weight ratio of lung tissue (4.16±0.66) was reduced in the high-dose group (P=0.003). Levels of IL-6, IL-1β and TNF-α[ (187.98±53.28) pg/ml, (92.45±25.39) pg/ml, (129.77±55.94) pg/ml] were reduced (P=0.001, 0.027, 0.018), and relative protein expression levels of p-PI3K, p-AKT and p-ERK1/2 (0.65±0.05, 0.31±0.08, 1.30±0.12) were reduced (P=0.013, 0.018, 0.015) . Conclusion: Liangge Powder has therapeutic effects in rats with sepsis-induced ALI, and the mechanism may be related to the inhibition of ERK1/2 and PI3K/AKT pathway activation in lung tissue.

Resveratrol Prevents Vibrio vulnificus-Induced Sepsis by Attenuating Necroptosis / 生物医学与环境科学（英文）

OBJECTIVE@#This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol (RSV) regulate necroptosis during Vibrio vulnificus (V. vulnificus)-induced sepsis and the potential mechanism.@*METHODS@#The effect of RSV on V. vulnificus cytolysin (VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V. vulnificus-induced sepsis mouse model.@*RESULTS@#RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells. RSV also inhibited the inflammatory response, had a protective effect on histopathological changes, and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages, lung, spleen, and liver tissues of V. vulnificus-induced septic mice in vivo. Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V. vulnificus-induced septic mice. RSV also improved the survival of V. vulnificus-induced septic mice.@*CONCLUSION@#Our findings collectively demonstrate that RSV prevented V. vulnificus-induced sepsis by attenuating necroptosis, highlighting its potency in the clinical management of V. vulnificus-induced sepsis.

Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection / 中华血液学杂志

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

Morphological investigation of protective effects of CDP-choline on liver and small intestine in an experimental sepsis model in rats / Investigación morfológica de los efectos protectores de la CDP-colina en el hígado y el intestino delgado en un modelo experimental de sepsis en ratas

SUMMARY: Fifty male Wistar albino rats were divided into 5 groups; Group 1 as a sham group. Group 2 as a control group, Group 3 as 100 mg/kg CDP-choline administered group, Group as 200 mg/kg CDP-choline administered group, and Group 5 as sepsis group. The sepsis model was performed by ligating and perforating the caecum of rats. Liver and small intestine tissues were assessed either histologically or quantitatively and qualitatively. There was a significant difference between the sepsis and CDP-choline groups for liver and intestinal damage evaluated in tissue samples. (p <0.001). CDP-choline treatment partially improved dose-dependent the clinical parameters of sepsis and septic shock, reversed micro-anatomical damage caused by sepsis.

Cincuenta ratas albinas Wistar macho se dividieron en 5 grupos; Grupo 1 como grupo control simulador, el grupo 2 como grupo de control, el grupo 3 como grupo al que se administró 100 mg/kg de CDP-colina, el grupo 4 como grupo al que se administró 200 mg/kg de CDP-colina y el grupo 5 como grupo con sepsis. El modelo de sepsis se realizó ligando y perforando el intestino ciego de las ratas. Los tejidos del hígado y del intestino delgado se evaluaron histológicamente o cuantitativa y cualitativamente. Hubo una diferencia significativa entre los grupos de sepsis y CDP-colina para el daño hepático e intestinal evaluado en muestras de tejido (p<0,001). El tratamiento con CDP-colina mejoró parcialmente, según la dosis, los parámetros clínicos de sepsis y shock séptico y revirtió el daño micro anatómico causado por la sepsis.

Current application of antibiotic de-escalation treatment in children with sepsis and its impact on prognosis / 中华儿科杂志

Objective: To analyze the eligibility of empirical antibiotic therapy in culture positive sepsis in the pediatric intensive care unit (PICU), and to explore the application of antibiotic de-escalation (ADE) in children with sepsis and its impact on prognosis. Methods: A total of 123 children with sepsis-associated organ dysfunction or septic shock admitted to the PICU of Shengjing Hospital of China Medical University from January 2018 to December 2020 were retrospectively analyzed. The general information, laboratory tests, the use of empirical anti-bacterial drugs and the application of ADE were collected. According to the adjustment of anti-bacterial drugs, these children were divided into ADE group and non-ADE group. Comparisons between groups were performed with unpaired Student t test, or Mann-Whitney U test, or chi-square test or Fisher exact test. Results: In these 123 children, 70 were males and 53 were females, the age was 11.4 (2.8, 56.5) months. Body fluid culture was detected positive in 41 children including 3 children (7.3%) who received inadequate empirical antibiotic therapy and 38 children (92.7%) who received adequate empirical antibiotic therapy. Excluding 10 children who received appropriate therapy, 28 received unnecessary broad-spectrum antibiotics. There were no significant differences regarding the PICU all-cause mortality rates, length of PICU stay, hospitalization cost, duration of mechanical ventilation, as well as incidences of re-infection between the ADE group (n=46) and non-ADE group (n=77) (all P>0.05). However, among the 101 children who have used antibiotics against multidrug-resistant organism, the duration of such antibiotics use in ADE group (n=43) was shorter than that in non-ADE group (n=58) (5.0 (4.0, 12.0) vs. 9.5 (7.0, 13.0) d, Z=-3.14, P=0.002). Conclusions: Overuse of unnecessary broad-spectrum empirical antibiotics is very common, but the application of ADE is rather disappointing. ADE can reduce the use of anti-bacterial drugs against multi-drug resistant bacteria without significant adverse effects on prognosis in children with sepsis.

Single Center Clinical Analysis of Bloodstream Infection Pathogens in Children with Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features, distribution of pathogenic bacteria, and drug resistance of bloodstream infection in children with acute leukemia.@*METHODS@#Clinical data of 93 blood culture-positive children with acute leukemia from January 2015 to December 2019 in Department of Pediatrics, The Second Hospital of Anhui Medical University were analyzed retrospectively.@*RESULTS@#In these 93 cases, 78 cases were in the period of neutrophil deficiency. There were 54 Gram-negative bacteria (G-) (58.1%) found through blood culture, and the top 4 strains were Escherichia coli (15.1%), Klebsiella pneumoniae (13.9%), Pseudomonas aeruginosa (6.5%), and Enterobacter cloacae (6.5%). There were 39 Gram-positive bacteria (G+) (41.9%) detected, and the top 4 strains were Staphylococcus epidermidis (10.8%), Streptococcus pneumoniae (6.5%), Staphylococcus hemolyticus (5.4%), and Staphylococcus human (5.4%). Among 74 strains of pathogenic bacteria from acute lymphoblastic leukemia (ALL) children, there were 29 strains of G+ bacteria (39.2%) and 45 strains of G- bacteria (60.8%). While in 19 strains from acute myeloblastic leukemia (AML) patients, G- bacteria accounted for 47.4% and G+ bacteria accounted for 52.6%. In 15 ALL children without neutropenia, G+ bacteria made up the majority of the strains (66.7%). In the 93 strains of pathogenic bacteria, 13 (13.9%) strains were multidrug-resistant. Among them, extended-spectrum β-lactamases accounted for 42.9%, carbapenemase-resistant enzyme Klebsiella pneumoniae 15.4%, and carbapenemase-resistant enzyme Enterobacter cloacae strains 33.3%, which were detected from G- bacteria. While, 13.3% of methicillin-resistant coagulase-negative Staphylococci accounted for 13.3% detected from G+ bacteria, but linezolid, vancomycin, teicoplanin Staphylococcus and Enterococcus resistant were not found. The average procalcitonin (PCT) value of G- bacteria infection was (11.02±20.282) ng/ml, while in G+ infection it was (1.81±4.911) ng/ml, the difference was statistically significant (P<0.05). The mean value of C-reactive protein (CRP) in G- infection was (76.33±69.946) mg/L, and that in G+ infection was (38.34±57.951) mg/L. The prognosis of active treatment was good, and only one case died of septic shock complicated with disseminated intravascular coagulation (DIC) and gastrointestinal bleeding caused by carbapenemase-resistant enzyme enterobacteriaceae.@*CONCLUSION@#G- is the major bacteria in acute leukemia children with bloodstream infection, but the distribution of ALL and AML strains is different. G- bacteria dominates in ALL, while G+ bacteria and G- bacteria are equally distributed in AML. Non-agranulocytosis accompanied by bloodstream infections is dominant by G+ bacteria. The mean value of PCT and CRP are significantly higher in G- bacteria infection than in G+ bacteria.

Distribution and drug resistance profiles of pathogens causing bloodstream infection after chemotherapy in children with acute lymphoblastic leukemia / 中国当代儿科杂志

OBJECTIVES@#To study the changes in the distribution and drug resistance profiles of pathogens causing bloodstream infection after chemotherapy in children with acute lymphoblastic leukemia.@*METHODS@#The medical data were collected from the children with acute lymphoblastic leukemia who were admitted to the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2020 and developed bloodstream infection after chemotherapy. The samples were divided into the first three years group and the next three years group according to the time of testing to investigate the differences in the distribution and drug resistance profiles of pathogens as time.@*RESULTS@#A total of 235 strains of pathogens were isolated, among which there were 159 Gram-negative strains (67.7%; mainly Escherichia coli and Klebsiella pneumoniae), 61 Gram-positive strains (26.0%; mainly Staphylococcus epidermidis), and 15 strains of fungi (6.4%; mainly Candida albicans). There were no significant differences between the first three years group and the next three years group in the detection rate of Gram-negative bacteria (68.8% vs 66.9%, P>0.05) or Gram-positive bacteria (29.2% vs 23.7%, P>0.05). Compared with the first three years group, the next three years group had significant increases in the detection rate of Streptococcus mitis (5.8% vs 0.0%, P<0.05) and fungi (9.4% vs 2.1%, P<0.05). There was no significant difference in the drug resistance rate of Gram-negative or Gram-positive bacteria between the two groups (P>0.05).@*CONCLUSIONS@#Enterobacteriaceae bacteria are the main pathogens of bloodstream infection after chemotherapy in children with acute lymphoblastic leukemia, while the detection rates of Streptococcus mitis and fungi tend to increase as time, which needs to be taken seriously in clinical practice.

Randomized controlled trial outcome indicators of traditional Chinese medicine for gastrointestinal dysfunction in sepsis in recent two years / 中国中药杂志

The purpose of the study is to analyze the outcomes of randomized controlled trial(RCT) of Chinese herbal medicine formula(CHMF) in the treatment of gastrointestinal dysfunction in sepsis in recent two years. We systematically searched four Chinese databases, three English databases, and two clinical trial registries to analyze the reports of outcome indicators of clinical trials, and evaluated the risk of bias by using the ROB tool of Cochrane Collaboration. After screening, 55 clinical RCTs were included. The results showed that the current clinical studies of gastrointestinal dysfunction in sepsis reported the efficacy and safety indicators. The efficacy indicators included APACHE Ⅱ scores, gastrointestinal dysfunction scores, bowel sound scores, and inflammatory indicator such as C-reactive protein and procalcitonin. The safety indicators mainly include gastrointestinal reactions, skin reactions, and other adverse events and adverse reactions. However, there was no distinction between primary and secondary outcomes. The relevant indicators of health economics were not reported, and the quality of research methodology was poor. Therefore, we suggest that future researchers should be well prepared in the top-level design stage and actively construct the core outcome set, so as to improve the quality of clinical trials.

Temporal trend in early sepsis in a very low birth weight infants' cohort: an opportunity for a rational antimicrobial use

Abstract Objective This study aimed to evaluate annual trends of early neonatal sepsis and antimicrobial use in very low birth weight infants for 12 years, as well as to identify microbiological agents, antimicrobial sensitivity profiles, and association with early neonatal death. Method This was a retrospective cohort study including 1254 very low birth weight infants admitted from 2006 to 2017. Four groups were evaluated: culture-confirmed sepsis; presumed neonatal sepsis; ruled out neonatal sepsis group; and infants not exposed to antibiotics. Results The medians of gestational age and birth weight were 29 weeks (27-31) and 1090 g (850-1310), respectively. The rates of culture-confirmed sepsis, presumed neonatal sepsis, ruled out neonatal sepsis, and not exposed to antibiotics were 1.3, 9.0, 15.4, and 74.3%, respectively. From the initial group of newborns whose antimicrobial treatment was administered for sepsis' suspicion, it was possible to discontinue antibiotic in 44%. The culture-confirmed sepsis rates remained stable (p = 0.906). Significant tendencies of decreasing presumed sepsis rates (p < 0.001) and increased ruled out neonatal sepsis/not exposed to antibiotics rates (p < 0.001) were observed. Streptococcus agalactiae and enteric Gram-negative rods were the predominant agents and most of them were sensitive to crystalline penicillin/ampicillin (88.2%) and to ampicillin and/or amikacin. Early death occurred in 10.8%, specifically in the culture-confirmed sepsis and presumed neonatal sepsis groups. Conclusion The confirmed sepsis rate was low and remained stable. There was a significant downward trend in the presumed neonatal sepsis rate and a significant upward trend in the ruled out neonatal sepsis group. The rate of not exposed to antibiotics infants was high, also presenting a significant downward trend. The identified bacteria were those commonly found and showed usual antimicrobial susceptibility patterns. Death predominantly occurred in groups that received antibiotic treatment.

Bradicardia sinusal inducida por corticoesteroides en un niño con insuficiencia suprarrenal y septicemia / Corticosteroid-induced sinus bradycardia in a young boy with adrenal insufficiency and sepsis

La bibliografía no incluye frecuentemente alteraciones en el ritmo cardíaco de los pacientes que reciben corticoesteroides; se desconoce su mecanismo exacto. En este artículo, presentamos el caso de un paciente con bradicardia sinusal asociada con una dosis de estrés de corticoesteroides. Se ingresó a un niño de 9 años con antecedentes de panhipopituitarismo con gastroenteritis y neumonía y presentó choque septicémico el día de la hospitalización. El tratamiento con líquidos intravenosos, dosis de estrés de hidrocortisona y antibióticos permitió la recuperación. Sin embargo, luego se documentó bradicardia sinusal con una frecuencia cardíaca de 45 latidos por minuto. Esta se resolvió después de reducir gradualmente la hidrocortisona. La bradicardia sinusal inducida por corticoesteroides es un efecto adverso que suele resolverse tras interrumpir el tratamiento. Se debe considerar el monitoreo hemodinámico en estos casos. Este es el primer informe de bradicardia sinusal posterior al uso de hidrocortisona en niños con insuficiencia suprarrenal

The literature does not commonly describe cardiac rhythm disturbances, including bradycardia, in patients who are receiving corticosteroids, and the exact mechanism of such disturbances remains unknown. Herein, we present a case of sinus bradycardia associated with stress-dose corticosteroid therapy. A nine-year-old boy with a history of panhypopituitarism was admitted with gastroenteritis and pneumonia and developed septic shock on the day of admission. Management using intravenous fluids, stress doses of hydrocortisone, and antibiotics resulted in full recovery. However, within 24 hours following treatment, sinus bradycardia was documented, with a heart rate of 45 beats per minute (BPM). The bradycardia resolved after the dose of hydrocortisone was decreased gradually. Corticosteroidinduced sinus bradycardia is an adverse effect that usually resolves after corticosteroid treatment is discontinued. During stress-dose corticosteroid therapy, hemodynamic monitoring should be considered. To our knowledge, this is the first report of sinus bradycardia following the use of hydrocortisone in children who have adrenal insufficiency.

Atractylenolide III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein

ABSTRACT Purpose: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. Methods: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). Results: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. Conclusions: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

Beneficial role of oleuropein in sepsis-induced myocardial injury. Possible Involvement of GSK-3β/NF-kB pathway

ABSTRACT Purpose The present study explored the potential therapeutic role of oleuropein in sepsis-induced heart injury along with the role of GSK-3β/NF-kB signaling pathway. Methods Sepsis-induced myocardial injury was induced by cecal ligation and puncture (CLP) in rats. The cardiac injury was assessed by measuring the levels of cTnI and creatine kinase-MB (CK-MB). Sepsis-induced inflammation was assessed by measuring interleukin-6 (IL-6), IL-10 and HMGB1 levels. The different doses of oleuropein (5, 10, and 20 mg/kg) were given prior to CLP. Oleuropein (20 mg/kg) was administered after 6 hof CLP. The expressions of GSK-3β, p-GSK-3β (Ser9) and nuclear factor-κB (NF-κB) were measured in heart homogenates. Results Cecal ligation and puncture was associated with myocardial injury, an increase in IL-6, a decrease in IL-10 and an increase in HMGB1. Moreover, it decreased the ratio of p-GSK-3β/GSK-3β and increased the expression of p-NF-kB. Pretreatment with oleuropein attenuated CLP-induced myocardial injury and systemic inflammation in a dose-dependent manner. Administration of oleuropein after the onset of CLP also attenuated cardiac injury and inflammation. It also restored CLP-induced changes in the HMGB1 levels, the ratio of p-GSK-3β/GSK-3β and expression of p- NF-kB. Conclusions Oleuropein attenuates sepsis-induced systemic inflammation and myocardial injury by inhibiting NF-kB and GSK-3β signaling.

Astragaloside IV Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway / 中国结合医学杂志

OBJECTIVE@#To evaluate the protective effects of Astragaloside IV (AST) in a rat model of myocardial injury induced by cecal ligation and puncture (CLP).@*METHODS@#The model of sepsis-induced cardiac dysfunction was induced by CLP. Using a random number table, 50 specific pathogen free grade of Sprague Dawley rats were randomized into 5 groups: the sham group (sham), the model group (CLP, 18 h/72 h) and AST group (18 h/72 h). Except the sham group, the rats in other groups received CLP surgery to induce sepsis. CLP groups received intragastric administration with normal saline after CLP. AST groups received intragastric administration with AST solution (40 mg/kg) once a day. The levels of inflammatory mediators and oxidative stress markers in the serum of the septic rats were determined via enzyme-linked immunosorbent assay (ELISA) at different time point, such as interleukin 6 (IL-6), IL-10, high mobility group box-1 protein B1 (HMGB-1), superoxide dismutase (SOD), and malondialdehyde (MDA). Cardiac function was determined by echocardiography. Moreover, changes in myocardial pathology were evaluated using hematoxylin and eosin staining. The levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were analysed to determine the status of CLP-induced myocardium. In addition, the apotosis of myocardial cells was analysed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), IκB kinase α (IKKα), nuclear factor kappa B p65 (NF-κB p65) were detected by Western blot analysis. Moreover, survival rate was investigated.@*RESULTS@#AST improved the survival rate of CLP-induced rats by up to 33.3% (P<0.05). The cardioprotective effect of AST was observed by increased ejection fraction, fractional shortening and left ventricular internal diameter in diastole respectively (P<0.01 or P<0.05). Subsequently, AST attenuated CLP-induced myocardial apoptosis and the ratio of Bcl-2/Bax in the myocardium, as well as the histological alterations of myocardium (P<0.01 or P<0.05); the generation of inflammatory cytokines (IL-6, IL-10, HMGB-1) and oxidative stress markers (SOD, MDA) in the serum was significantly alleviated (P<0.01 or P<0.05). On the other hand, AST markedly suppressed CLP-induced accumulation of IKK-α and NF-κB p65 subunit phosphorylation (P<0.01 or P<0.05).@*CONCLUSIONS@#AST plays a significant protective role in sepsis-induced cardiac dysfunction and survival outcome. The possible mechanism of cardioprotection is dependent on the activation of the IKK/NF-κB pathway in cardiomyocytes.

Immunomodulator use in paediatric severe sepsis and septic shock

INTRODUCTION@#The use of drugs that modulate the immune system during paediatric severe sepsis and septic shock may alter the course of disease and is poorly studied. This study aims to characterise these children who received immunomodulators and describe their clinical outcomes.@*METHODS@#This is a retrospective chart review of patients with severe sepsis and septic shock admitted into the paediatric intensive care unit (PICU). Clinical, haematological and outcome characteristics of patients with or without exposure to immune-modulating drugs were compared. Primary outcome was PICU mortality; secondary outcomes were 28-day ventilator-free days (VFD) and intensive care unit-free days (IFD). Univariate and multivariable analyses were performed for these outcomes.@*RESULTS@#A total of 109 patients with paediatric severe sepsis or septic shock were identified. Of this number, 47 (43.1%), 16 (14.7%) and 3 (2.8%) patients received systemic corticosteroids, intravenous immunoglobulins and granulocyte colony stimulating factor, respectively. Patients who received immune-modulating drugs were more likely to require invasive ventilation (38/54 [70.4%] versus 26/55 [47.3%], @*CONCLUSION@#Immune-modulating drugs were frequently used in paediatric severe sepsis and septic shock. Patients who received these drugs seemed to require more PICU support. Further studies are required to examine this association thoroughly.

Sepsis risk calculator-guided antibiotic management in neonates with suspected early-onset sepsis / 中国当代儿科杂志

OBJECTIVE@#To evaluate the efficacy of sepsis risk calculator (SRC) in guiding antibiotic use in neonates with suspected early-onset sepsis (EOS).@*METHODS@#A total of 284 neonates with a gestational age of ≥ 35 weeks were enrolled as the control group, who were hospitalized in the Children's Hospital of Chongqing Medical University from March to July, 2019 and were suspected of EOS. Their clinical data were retrospectively collected and the use of antibiotics was analyzed based on SRC. A total of 170 neonates with a gestational age of ≥ 35 weeks were enrolled as the study group, who were admitted to the hospital from July to November, 2020 and were suspected of EOS. SRC was used prospectively for risk scoring to assist the decision making of clinical antibiotic management. The two groups were compared in terms of the rate of use of antibiotics, blood culture test rate, clinical outcome, and adherence to the use of SRC.@*RESULTS@#Compared with the control group, the study group had a significantly higher SRC score at birth and on admission (@*CONCLUSIONS@#The use of SRC reduces the rate of empirical use of antibiotics in neonates with suspected EOS and does not increase the risk of adverse outcomes, and therefore, it holds promise for clinical application.