To determine whether infection-prevention and control (IPC) interventions can reduce the colonisation and infection of intensive care unit (ICU)-acquired carbapenem-resistant Klebsiella pneumoniae (CRKP) in a general ICU ward in China. We used a quasi-experimental before-and-after study design. The study was conducted in 4 stages: baseline period, January 2013–June 2013; IPC interventions period including de-escalation and targeted bundle interventions, July 2013–June 2014; modified IPC interventions period, July 2014–June 2015; and follow-up period, July 2015–June 2016. We used modified de-escalation interventions according to patient-risk assessments to prevent the transmission of CRKP. A total of 629 patients were enrolled in study. The incidence of ICU-acquired CRKP colonisation/infection was 10.08 (4.43–16.43) per 1000 ICU patient-days during the baseline period, and significantly decreased early during the IPC interventions, but the colonisation/infections reappeared in April 2014. During the modified IPC intervention and follow-up periods, the incidence of ICU-acquired CRKP colonisations/infections reduced to 5.62 (0.69–6.34) and 2.84 (2.80–2.89), respectively, with ongoing admission of cases with previously acquired CRKP. The incidence of ICU-acquired CRKP catheter-related bloodstream infections decreased from 2.54 during the baseline period to 0.41 during the follow-up period. The incidence of ventilator-associated pneumonia and skin and soft tissue infections showed a downward trend from 2.84 to 0.41 and from 3.4 to 0.47, respectively, with slight fluctuations. Comprehensive IPC interventions including de-escalation and targeted bundle interventions showed a significant reduction in ICU-acquired CRKP colonisations/infections, despite ongoing admission of patients colonised/infected with CRKP.

Background/Objectives: Abnormal bile acid (BA) pool may play an important role in inducing liver damage in sepsis. Farnesoid X receptor (FXR) is a main negative feedback regulator of BA metabolism. This study aims to explore the protective effect and mechanism of the FXR agonist obeticholic acid (OCA) on liver dysfunction when sepsis occurs. Methods: A rat model of sepsis was induced by cecal ligation and puncture (CLP) for 24 h. Systematic inflammation, tissue injury, hepatic FXR, and BA transporter expression were investigated in the CLP rats and sham-operated control rats with and without OCA pre-treatment (10 mg/kg, gavage) at 2 h before operation. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay was performed to access BA composition in the rats’ serum and livers. The injury and inflammatory effects of the elevated unconjugated BAs found in the CLP rats was further verified in a hepatic cell line BRL-3A in vitro. Results: Hepatic FXR was repressed in CLP rats, whereas OCA upregulated liver FXR and hepatic BA transporter expression, reduced total serum BA concentration, ameliorated the elevation of serum levels of IL-1β and IL-6, and improved liver and ileal tissue injuries. OCA administration reduced the elevated unconjugated BAs in both serum and liver, and effectively inhibited increases in cholic acid (CA), deoxycholic acid (DCA), and 7-ketoDCA concentrations in CLP rat livers. These BA fractions promoted the release of aspartate aminotransferase (AST) from BRL-3A cells and increased IL-6, CXCL2, and monocyte chemoattractant protein-1 (MCP-1) expression in the cells, along with enhanced transcription factor nuclear factor-κB activation. Conclusions: Liver inflammation and dysfunction during sepsis is attributable to significant changes in bile acid composition in the blood and liver. FXR activation reduces systemic inflammation and liver dysfunction by regulating bile acid homeostasis, especially inflammatory unconjugated bile acid components.

Introduction: Diabetes is an independent risk factor for the development of severe community-acquired pneumonia (CAP) and associated with pneumonia-related hospitalization as well as mortality. Here, we assessed several selected biomarkers to determine their predictive value for progression to severe CAP among diabetic patients. Research design and methods: A retrospective cohort study of diabetic patients with CAP was conducted at a tertiary teaching hospital. The prediction model group (N=100) comprised patients registered between January 2015 to December 2016. Multivariate analysis was performed to identify predictive biomarkers from this cohort. The validation group (N=108) comprised the patients between January 2017 to February 2019. Predictive performance was assessed in the validation group. Results: A total of 208 diabetic inpatients with CAP were recruited. Further multivariate analysis showed that C-reactive protein (CRP), absolute lymphocyte count (ALC), immunoglobulin (IgM), and HbA1C at admission were independently associated with progression to severe CAP in diabetic patients during hospitalization. The prediction model =0.0179555*CRP+1.975918* HbA1C-2.879364* ALC -0.026255* IgM -8.220555. The area under ROC (AUROC) curve in the validation group was 0.851 (0.781-0.921) with statistical significance (P<.05). Conclusions: In diabetic patients with CAP, a combination of CRP, ALC, IgM, and HbA1C at admission could be used to predict the progression to severe CAP.