Although Klebsiella pneumoniae bloodstream infections (KP-BSIs) have recently attracted attention due to an alarming raise in morbidity and mortality, there have been few reports on the epidemiology of KP-BSIs in mainland China. We sought to describe the epidemiological, microbiological, and clinical characteristics of KP-BSIs, focusing on the risk factors of carbapenem resistance and patient mortality. A retrospective analysis of WHONET data of KP-BSI patients admitted to a teaching hospital in Shanghai, China, between January 1, 2011 and December 31, 2015 was performed, and the annual percentage of patients with carbapenem-resistant K. pneumoniae (CRKP) was determined. Risk factors related to the carbapenem resistance and patient mortality were analyzed using binary logistic regression model. The genetic relatedness of CRKP strains isolated from intensive care unit (ICU) patients was determined by pulsed-field gel electrophoresis (PFGE). A total of 293 incidences of KP-BSIs were identified in a 5-year period, 22.18% of these (65/293) were CRKP strains, and the proportion of CRKP-BSI in ICU was 59.62% (31/52), equaling the levels observed in the epidemic regions. A number of KP-BSIs (114), obtained from January 1, 2014, to December 31, 2015, were further investigated. Skin and soft tissue infection source (odds ratio [OR] 26.63, 95% confidence interval [CI] 4.8–146.8) and ICU-acquired infection (OR 5.82, 95% CI 2.0–17.2) was shown to be powerful risk factors leading to the development of CRKP-BSI. The crude 28-day mortality rates of KP-BSI and CRKP-BSI patients were 22.8% and 33.3%, respectively. Lung as the probable source of infection (OR 4.23, 95% CI 1.0–17.3), and high Sequential Organ Failure Assessment (SOFA) score (OR 1.40, 95% CI 1.2–1.6) were strong prognostic factors determining crude 28-day KP-BSI mortality rates. PFGE analysis demonstrated that 10/11 random CRKP isolates in ICU belonged to the same clonal type. During the study period, we observed a significant increase in the occurrence of CRKP infections among the identified KP-BSIs in our hospital and especially in ICU, and we demonstrated that carbapenem resistance is associated with the increased mortality of KP-BSI patients.

Acute pancreatitis (AP) with infectious complications has high mortality because of early‐stage immunosuppression. The programmed cell death‐1 (PD‐1)/programmed cell death ligand 1 (PD‐L1) pathway is an important host immunosuppression mechanism. Soluble PD‐L1 (sPD‐L1) expression regulates co‐inhibitory signals in malignancies or autoimmune disorders; however, its effects in AP are unknown. Here, we evaluated whether serum sPD‐L1 is involved in immune dysfunction and assessed its relationship with infectious complications in early AP. Blood samples were obtained from 56 patients with acute pancreatitis and 21 healthy individuals in this prospective study. Serum sPD‐L1 levels within 48 h after AP onset were tested by enzyme‐linked immunosorbent assays. Relevant immune parameters (human leucocyte antigen‐DR, lymphocyte count) and inflammatory markers (C‐reactive protein, white blood cell count) were analysed. sPD‐L1 was significantly upregulated in patients with early AP, especially those with infectious complications, compared to healthy controls. Significant negative correlations were observed among monocyte HLA‐DR expression, lymphocyte count and sPD‐L1 levels in AP. Multivariate regression indicated that sPD‐L1 was an independent risk factor for infectious complications in AP. The findings suggest that increased sPD‐L1 expression appears to be involved in the development of immunosuppression in the early stage of AP and that sPD‐L1 might be an early parameter for prediction of infectious complications in patients with AP.

Sepsis is associated with significant mortality. Early diagnosis and prognosis of patients with sepsis is still a difficult clinical challenge. In this study, the ability of plasma PTX3 (pentraxin 3), MCP1 (monocyte chemoattractant protein 1) and Ang (angiopoietin)1/2 was investigated to evaluate the severity of sepsis. Blood samples were obtained from 43 patients with sepsis. A total of 33 post‐surgery patients with infections and 25 healthy individuals served as controls. The results showed that plasma PTX3, MCP1 and Ang2 significantly increased in patients on the first day of septic shock onset, while sepsis patients had significantly higher Ang2 level, compared with controls. Furthermore, PTX3, MCP1 and Ang2 had high AUROC values in patients with septic shock on the first day of sepsis onset. The findings suggest that PTX3, MCP1 and Ang2 maybe early predictors to evaluate the severity of sepsis and septic shock with the latest Sepsis 3.0 definitions.

Microcirculatory dysfunction is one of the main characteristics of sepsis. Shenfu Injection (SFI) as a traditional Chinese medicine is widely applied in clinical severe conditions. Recent studies have shown that SFI has the ability to ameliorate sepsis-induced inflammation and to improve microcirculation perfusion. This study aims to investigate the underlying mechanism of SFI for ameliorating sepsis-associated endothelial dysfunction and organ injury. Side-stream dark-field (SDF) imaging was used to monitor the sublingual microcirculation of septic patients treated with or without SFI. Septic mouse model was used to evaluate the effects of SFI in vivo. Metabolomics and transcriptomics were performed on endothelial cells to identify the underlying mechanism for SFI-related protective effect on endothelial cells. SFI effectively abolished the disturbance and loss of sublingual microcirculation in septic patients. Twenty septic shock patients with or without SFI administration were enrolled and the data showed that SFI significantly improved the levels of total vessel density (TVD), perfused vessel density (PVD), microvascular flow index (MFI), and the proportion of perfused vessels (PPV). The administration of SFI significantly decreased the elevated plasma levels of Angiopoietin-2 (Ang2) and Syndecan-1, which are biomarkers indicative of endothelial damage in sepsis patients. In the mouse septic model in vivo, SFI inhibited the upregulation of endothelial adhesion molecules and Ly6G + neutrophil infiltration while restored the expression of VE-Cadherin in the vasculature of the lung, kidney, and liver tissue. Additionally, SFI reduced the plasma levels of Ang2, Monocyte Chemoattractant Protein-1(MCP1), and Interleukin-6 (IL6), and alleviated liver and kidney injury in septic mice. Moreover, SFI significantly inhibited the inflammatory activation and increased permeability of endothelial cells induced by endotoxins in vitro. By performing metabolomics and transcriptomics, we identified the activation of PI3K/Akt-mediated glycolysis as the underlying mechanism for SFI-related protective effect on endothelial cells. Our findings revealed that SFI may improve microcirculation perfusion and endothelial function in sepsis via inhibiting PI3K/Akt-mediated glycolysis, providing theoretical evidence for the clinical application of SFI.