Antibiotic utilisation and resistance over the first decade of nationally funded antimicrobial stewardship programmes in Singapore acute-care hospitals.

OBJECTIVE: The aim of this study was to describe the time series of broad-spectrum antibiotic utilisation and incidence of antibiotic-resistant organisms during the implementation of antimicrobial stewardship programmes (ASP) in Singapore. METHODS: An observational study was conducted using data from 2011 to 2020 in seven acute-care public hospitals. We applied joinpoint regressions to investigate changes in antibiotic utilisation rate and incidence density of antibiotic-resistant organisms. RESULTS: Across the seven hospitals, quarterly broad-spectrum antibiotic utilisation rate remained stable. Half-yearly incidence density of antibiotic-resistant organisms with two joinpoints at first half (H1) of 2012 and second half (H2) of 2014 decreased significantly in the second and third period with a half-yearly percentage change (HPC) of -2.9% and - 0.5%, respectively. Across the five hospitals with complete data, half-yearly broad-spectrum antibiotic utilisation rate with one joinpoint decreased significantly from H1 of 2011 to H2 of 2018 (HPC - 4.0%) and H2 of 2018 to H2 2020 (HPC - 0.5%). Incidence density of antibiotic-resistant organisms decreased significantly in the two joinpoint periods from H1 of 2012 to H2 of 2014 (HPC - 2.7%) and H2 of 2014 to H2 of 2020 (HPC - 1.0%). Ceftriaxone with one joinpoint decreased significantly from H1 of 2011 to H1 of 2014 (HPC - 6.0%) and H1 of 2014 to H2 of 2020 (HPC - 1.8%) and ceftriaxone-resistant E. coli and K. pneumoniae decreased significantly in later periods, from H2 of 2016 to H2 of 2020 (HPC - 2.5%) and H1 of 2012 to H2 of 2015 (HPC - 4.6%) respectively. Anti-pseudomonal antibiotics with one joinpoint decreased significantly from H1 of 2011 to H2 of 2014 (HPC - 4.5%) and H2 of 2014 to H2 of 2020 (HPC - 0.8%) and that of quinolones with one joinpoint at H1 of 2015 decreased significantly in the first period. C. difficile with one joinpoint increased significantly from H1 of 2011 to H1 of 2015 (HPC 3.9%) and decreased significantly from H1 of 2015 to H2 of 2020 (HPC - 4.9%). CONCLUSIONS: In the five hospitals with complete data, decrease in broad-spectrum antibiotic utilisation rate was followed by decrease in incidence density of antibiotic-resistant organisms. ASP should continue to be nationally funded as a key measure to combat antimicrobial resistance in acute care hospitals.

Sustaining Antimicrobial Stewardship in a High-Antibiotic Resistance Setting.

Importance: There is a lack of studies comparing the intended and unintended consequences of prospective review and feedback (PRF) with computerized decision support systems (CDSS), especially in the longer term in antimicrobial stewardship. Objective: To examine the outcomes associated with the sequential implementation of PRF and CDSS and changes to these interventions with long-term use of antibiotics for and incidence of multidrug resistant organisms (MDROs) and other unintended outcomes. Design, Setting, and Participants: This cohort study used an interrupted time series with segmented regression analysis of data from January 2007 to December 2018. Data were extracted from the electronic medical records of patients admitted at a large university teaching hospital with high rates of antibiotic resistance in Singapore. Data were analyzed from June 2019 to June 2020. Exposures: PRF of piperacillin-tazobactam and carbapenems (intervention 1, April 2009), with the addition of hospital-wide CDSS (intervention 2, April 2011), and lifting of CDSS for half of the hospital wards for 6 months (intervention 3, March 2017). Main Outcomes and Measures: Monthly antimicrobial use was measured in defined daily doses (DDDs) per 1000 patient-days. The monthly incidence of MDROs was calculated as number of clinical isolates detected per 1000 inpatient-days over a 6-month period. Unintended outcomes examined included in-hospital mortality and age-adjusted length of stay (LOS). Results: The number of inpatients increased from 56 263 in 2007 to 63 572 in 2018. During the same period, the mean monthly patient days increased from 33 929 in 2007 to 45 603 in 2018, and the proportion of patients older than 65 years increased from 45.5% in 2007 to 56.6% in 2018. After intervention 1, there were 0.33 (95% CI, 0.18 to 0.48) more DDDs per 1000 patient-days per month of piperacillin-tazobactam and carbapenems and -11.05 (95% CI, -15.55 to -6.55) fewer DDDs per 1000 patient-days per month for other broad-spectrum antibiotics. After intervention 2, there were -0.22 (95% CI, -0.33 to -0.10) fewer DDDs per 1000 patient-days per month of piperacillin-tazobactam and carbapenems and -2.10 (95% CI, -3.13 to -1.07) fewer DDDs per 1000 patient-days per month for other broad-spectrum antibiotics. After intervention 3, use of piperacillin-tazobactam and carbapenem increased by 0.28 (95% CI, 0.02 to 0.55) DDDs per 1000 patient-days per month. After intervention 2, incidence of Clostridioides difficile decreased (estimate, -0.02 [95% CI, -0.03 to -0.01] cases per 1000 patient-days per month). Conclusions and Relevance: In this cohort study, concurrent PRF and CDSS were associated with limiting the use of piperacillin-tazobactam and carbapenems while reducing use of other antibiotics.

NIHSS-the Alberta Stroke Program Early CT Score mismatch in guiding thrombolysis in patients with acute ischemic stroke.

OBJECTIVE: This study investigates the mismatch between the National Institutes of Health Stroke Scale (NIHSS) score and the computed tomography (CT) findings measured by the Alberta Stroke Program Early CT Score (ASPECTS) for predicting the functional outcome and safety of intravenous thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS). METHODS: This prospective observational study includes patients with AIS who underwent CT imaging within 4.5 h of the onset of symptoms. Patients were divided into the NIHSS-ASPECTS mismatch (NAM)-positive and NAM-negative groups (group P and N, respectively). The clinical outcome was assessed using the Modified Rankin Scale (mRS). Safety outcomes included progression, symptomatic intracerebral hemorrhage (sICH), intracerebral hemorrhage (ICH), adverse events, clinical adverse events, and mortality. RESULTS: A total of 208 patients were enrolled in the study. In group P, IVT treatment was associated with a good functional outcome at 3 months (p = 0.005) and 1 year (p = 0.001). A higher percentage of patients with favorable mRS (0-2) (p = 0.01) and excellent mRS (0-1) (p = 0.011) functional outcomes was obtained at 1 year in group P with IVT treatment. Group N did not benefit from the same treatment (p = 0.352 and p = 0.480 at 3 months and 1 year, respectively). There were no statistically significant differences in sICH, ICH, mortality rates, or other risks between the IVT and conventional treatment groups. CONCLUSION: IVT treatment is associated with a good functional outcome in patients with NAM, without increasing the risks of sICH, ICH, mortality, or other negative outcomes. NAM promises to be an easily obtained indicator for guiding the treatment decisions of AIS.

Analysis of influencing factors of multi-site work-related musculoskeletal disorders in surgeons / 中国职业医学

@# Objective - - To analyze the prevalence and influencing factors of multi site work related musculoskeletal disorders （ ） Methods WMSDs in surgeons. A total of 102 surgeons from four hospitals were selected as study subjects by convenient sampling method. The Chinese version of Musculoskeletal Disorders Questionnaire was used to investigate the prevalence of ， Results WMSDs in the past one year the related individuals and occupational factors. The total prevalence of WMSDs among （ ）， （ ） （ ） surgeons was 54.9%. The top three sites were neck 48.0% lower back 35.3% and shoulder 32.4% . The prevalence of （ vs ，P ） WMSDs in multiple sites was higher than that in a single site 43.1% 11.8% <0.01 . Multivariate logistic regression ， ， analysis showed that surgeons who smoked were tired at work and had a bent back had a higher risk of developing WMSDs ［ （ - ）， （ - ）， （ - ）， P ］ odds ratios and 95% confidence intervals were 3.66 1.41 9.46 8.33 2.15 32.20 and 18.74 2.14 166.77 all <0.01 Conclusion - after excluding the influence of confounding factors. The prevalence rate of multi site WMSDs among surgeons is ， high and the influencing factors include bad living habits and occupational factors such as working load and working posture.

Effect and mechanism of Qifu Yin regulation of JAK2/STAT3 pathway to improve type 2 diabetic cognitive impairment / 中国药理学通报

Objective To explore the regulatory effeet of Qifu Yin ( QFY) on JAK2/STAT3 pathway in rats with type 2 diabetic cognitive impairment.Methods A small dose of STZ combined with high-fat and high- sugar feed was used to build the model.After success, they were divided into model group, QFY low-dose, high-dose group, and metformin group.After four weeks of intervention, fasting blood glucose ( FBG ) was measured; Morris water maze was used to detect spatial learning and memory ability in rats; Nissl staining and immunofluorescence staining were respectively used to detect the degree of brain injury and the expression of lba-1 , a marker of microglia .EL1SA was used to detect the expression of TNF-cx, IL6, ILK) and BDNF.Western blot was employed to detect the expression of JAK2/STAT3 pathway.Results Compared with the control group, the model group showed significant increase in blood glucose, decreased spatial learning and memory capacity, severely damaged hipp-ocampal neurons, increased activated microglia, significantly higher levels of TNF-cx, 1L6, p-JAK2/JAK2 and p-STAT3/STAT3, and signif icantly lower levels of ILK) and BDNF.Compared with the model group, QFY group effectively reduced FBG, inhibited the con-tinuous rise of FBG, improved learning and memory a- bility, improved hippocampal neuronal damage, reduced activated microglia, reduced TNF-cx, 1L6, p- JAK2/JAK2 and p-STAT3/STAT3 levels, and increased ILK) and BDNF levels.Conclusion QFY has been shown to improve type 2 diabetic cognitive impairment , and the mechanism may be related to the inhibition of blood glucose rise and regulation of the JAK2/STAT3 pathway, thereby inhibiting microglia activation.

Case-crossover study on association between temperature and non-accidental mortality in Tibet Plateau, China / 环境与职业医学

Background Under the background of global climate change, temperature has increased dramatically. Most studies about association between temperature and human health are conducted in low-altitude areas, but rarely focus on plateau areas. Objective To examine the association between temperature and non-accidental mortality risk in Tibet Plateau, China and to identify vulnerable populations for formulating targeted policies of climate change adaptation. Methods The mortality data, meteorological data, and pollutant data of Tibet area between 2013 to 2019 were collected. Based on time-stratified case-crossover design, conditional logistic regression models were used to analyze the exposure-response relationship between temperature and cause-specific mortality, which was linearized to obtain excess risk for 1 ℃ change; attributable fraction was calculated for assessing burden attributable to temperature; and stratified analyses were further conducted by gender, age (＜65 years old, ≥65 years old), and causes of death (cardiovascular diseases, cerebrovascular diseases, and respiratory diseases). Sensitivity analyses were conducted by adjusting model parameters and variables. Results A total of 26 045 non-accidental deaths were collected in Tibet during 2013 and 2019, and the P50 of temperature was 5.0 ℃. The non-accidental mortality risk increased as temperature become colder. A 1 ℃ decrease in temperature was associated with a 2.01% (95%CI: 0.94%-3.07%) increase in total non-accidental mortality, while the association changed to 2.05% (95%CI: 0.62%-3.47%) for male and 1.96% (95%CI: 0.34%-3.56%) for female, both of statistial significance; 1.45% (95%CI: −0.10%-2.98%) for the people <65 years old (not of significance) and 2.52% (95% CI : 1.04%-3.99%) for the people ≥65 years old (of significance); the excess risk for cardiovascular mortality was 2.65% (95%CI: 1.03%-4.24%), for cerebrovascular mortality was 3.70% (95%CI: 0.74%-6.57%), both of statistical significance, and for respiratory mortality was 2.18% (95%CI: −0.14%-4.44%), without significance. The total attribution number of non-accidental mortality was 5340 (95%CI: 2719-7528), and the total attributable fraction was 20.50% (95%CI: 10.44%-28.91%). The attributable fractions were higher in specific subgroups like male (20.72%), people ≥65 years (23.33%), and people with cardiovascular diseases (26.07%). Conclusion The exposure-response relationship between temperature and non-accidental mortality in Tibet showes that the non-accidental mortality risk increase as temperature become colder. The attributable burden of disease is heavy. Residents being male, ≥65 years, with cardiovascular diseases and respiratory diseases may be vulnerable to nonoptimal temperature.

Hospital Pharmacists and Antimicrobial Stewardship: A Qualitative Analysis.

Antimicrobial stewardship programmes (ASPs) in hospitals are predominantly led by specific ASP physicians and pharmacists. Limited studies have been conducted to appreciate non-ASP-trained hospital pharmacists' perspectives on their roles in antimicrobial stewardship. Focus group discussions (FGDs) were conducted with 74 pharmacists, purposively sampled from the 3 largest acute-care public hospitals in Singapore, to explore facilitators and barriers faced by them in antimicrobial stewardship. Applied thematic analysis was conducted and codes were categorised using the social-ecological model (SEM). At the intrapersonal level, pharmacists identified themselves as reviewers for drug safety before dispensing, confining to a restricted advisory role due to lack of clinical knowledge, experience, and empowerment to contribute actively to physicians' prescribing decisions. At the interpersonal level, pharmacists expressed difficulties conveying their opinions and recommendations on antibiotic therapy to physicians despite frequent communications, but they assumed critical roles as educators for patients and their caregivers on proper antibiotic use. At the organisational level, in-house antibiotic guidelines supported pharmacists' antibiotic interventions and recommendations. At the community level, pharmacists were motivated to improve low public awareness and knowledge on antibiotic use and antimicrobial resistance. These findings provide important insights into the gaps to be addressed in order to harness the untapped potential of hospital pharmacists and fully engage them in antimicrobial stewardship.

Effects of coronavirus disease 2019 (COVID-19) pandemic on antimicrobial prevalence and prescribing in a tertiary hospital in Singapore.

BACKGROUND: The deployment of antimicrobial stewardship (AMS) teams to deal with the COVID-19 pandemic can lead to a loss of developed frameworks, best practices and leadership resulting in adverse impact on antimicrobial prescribing and resistance. We aim to investigate effects of reduction in AMS resources during the COVID-19 pandemic on antimicrobial prescribing. METHODS: One of 5 full-time equivalent AMS pharmacists was deployed to support pandemic work and AMS rounds with infectious disease physicians were reduced from 5 to 2 times a week. A survey in acute inpatients was conducted using the Global Point Prevalence Survey methodology in July 2020 and compared with those in 2015 and 2017-2019. RESULTS: The prevalence of antimicrobial prescribing (55% in 2015 to 49% in 2019 and 47% in 2020, p = 0.02) and antibacterials (54% in 2015 to 45% in 2019 and 42% in 2020, p < 0.01) have been reducing despite the pandemic. Antimicrobial prescribing in infectious disease wards with suspected or confirmed COVID-19 cases was 29% in 2020. Overall, antimicrobial prescribing quality indicators continued to improve (e.g. reasons in notes, 91% in 2015 to 94% in 2019 and 97% in 2020, p < 0.01) or remained stable (compliance to guideline, 71% in 2015 to 62% in 2019 and 73% in 2020, p = 0.08). CONCLUSION: During the COVID-19 pandemic, there was no increase in antimicrobial prescribing and no significant differences in antimicrobial prescribing quality indicators.

Validation of Vancomycin Dosing Guidance During Transition of Care.

Vancomycin is an antibiotic commonly used to treat serious gram-positive infections. Patients requiring prolonged therapy in Singapore routinely receive intermittent vancomycin infusion in the hospital and are switched to continuous infusion for outpatient parenteral antibiotic therapy. During this transition of care, there may be a risk of not achieving therapeutic targets. We evaluated the performance of a model-based dosing algorithm in achieving a therapeutic target within 7 days of care transition. A published population pharmacokinetic model was used as the foundation to guide vancomycin dosing when discharging inpatients on intermittent infusion to outpatient care on continuous infusion. Selected demographic variables (age, weight, and creatinine clearance) were used to devise initial dosing. Patients with guided dosing were compared with historic controls (dosing by clinicians alone). The primary outcome of the study was to achieve vancomycin steady-state concentration of 20-25 mg/L. Compared with historic controls, the proportion of patients attaining a therapeutic target by day 7 was significantly improved (6 of 19 [31.6%] vs 12 of 17 [70.6%], P = .04). Our model-based approach could guide customized dosing to facilitate switching patients from intermittent to continuous infusion during transition of care. Further validation in a larger patient cohort is warranted.

A point prevalence survey to assess antibiotic prescribing in patients hospitalized with confirmed and suspected coronavirus disease 2019 (COVID-19).

BACKGROUND: Earlier studies have reported high antibiotic use in patients hospitalised for coronavirus disease 2019 (COVID-19), resulting in concerns of increasing antimicrobial resistance with increase antibiotic use in this pandemic. Point prevalence survey (PPS) can be a quick tool to provide antibiotic prescribing information to aid antimicrobial stewardship (AMS) activities. OBJECTIVES: To describe antibiotic utilization and evaluate antibiotic appropriateness in COVID-19 patients using PPS. METHODS: Adapting Global-PPS on antimicrobial use, the survey was conducted in COVID-19 wards at 2 centres in Singapore on 22 April 2020 at 0800h. Patients on systemic antibiotics were included and evaluated for antibiotic appropriateness. RESULTS: Five hundred and seventy-seven patients were screened. Thirty-six (6.2%) patients were on antibiotics and which were started at median of 7 days (inter-quartile rate (IQR), 4, 11) from symptom onset. Fifty-one antibiotics were prescribed in these patients. Overall, co-amoxiclav (26/51, 51.0%) was the most often prescribed antibiotic. Thirty-one out of 51 (60.8%) antibiotic prescriptions were appropriate. Among 20 inappropriate prescriptions, 18 (90.0%) were initiated in patients with low likelihood of bacterial infections. Antibiotic prescriptions were more appropriate when reviewed by infectious diseases physicians (13/31 [41.9%] versus 2/20 [10.0%], p=0.015), and if reasons for use were stated in notes (31/31 [100.0%] versus 16/20 [80.0%], p=0.019). CONCLUSIONS: Despite low prevalence of antibiotic use among confirmed and suspected COVID-19 patients at 2 centres in Singapore, there was significant proportion of inappropriate antibiotics use where bacterial infections were unlikely. AMS teams can tailor stewardship strategies using PPS results.

Genetic diversity and antibacterial activity of endophytic fungi from Zanthoxylum nitidum / 中国中药杂志

In order to reveal the distribution and population characteristics of endophytic fungi from Zanthoxylum nitidum and the antibacterial potential,this study performed molecular identification and analyzed the genetic diversity and antibacterial activity of endophytic fungi from Z. nitidum in Guangxi. Through culture and molecular identification,35 strains,belonging to 15 genera,12 families,10 orders,4 classes,and 2 phyla,were isolated from various tissues of Z. nitidum,of which Colletotrichum and Fusarium were the dominant genera,respectively accounting for 20% of total strains. The diversity of endophytic fungi was significantly different among roots,stems,and leaves,as manifested by the significantly higher Shannon index( H') in stems( 1. 678) than in roots( 0. 882 1) and leaves( 0. 515 4). The antimicrobial activity analysis showed that 14. 28% of endophytic fungi inhibited at least one indicator pathogen. Among them,Fusarium sp. ZN-34 and Fusarium sp. ZN-26 separately demonstrated the strongest inhibitory effect on Escherichia coli and Staphylococcus aureus. In general,Fusarium sp. ZN-26 and Phialemoniopsis plurioloculosa ZN-35 were advantageous in suppressing the two bacteria owing to the broad spectrum and strong efficacy. In summary,Z. nitidum in Guangxi boasts rich endophytic fungi with the majority showing strong antibacterial activity,which can be used as candidates for the extraction and separation of basic antibacterial substances and the development of natural antibacterial agents.

Humanized Mouse as a Tool to Predict Immunotoxicity of Human Biologics.

Advancements in science enable researchers to constantly innovate and create novel biologics. However, the use of non-human animal models during the development of biologics impedes identification of precise in vivo interactions between the human immune system and treatments. Due to lack of this understanding, adverse effects are frequently observed in healthy volunteers and patients exposed to potential biologics during clinical trials. In this study, we evaluated and compared the effects of known immunotoxic biologics, Proleukin®/IL-2 and OKT3 in humanized mice (reconstituted with human fetal cells) to published clinical outcomes. We demonstrated that humanized mice were able to recapitulate in vivo pathological changes and human-specific immune responses, such as elevated cytokine levels and modulated lymphocytes and myeloid subsets. Given the high similarities of immunological side effects observed between humanized mice and clinical studies, this model could be used to assess immunotoxicity of biologics at a pre-clinical stage, without placing research participants and/or patients at risk.

Effect of platelet count on long-term prognosis of cerebral infarction.

OBJECTIVE: This study aimed to analyze the correlation between platelet (PLT) count and the modified Rankin scale (mRS) in patients with cerebral infarction (CI) at the later stage of rehabilitation, which can be used to guide the secondary prevention strategy of CI. METHODS: A total of 180 CI patients were divided into three groups according to PLT count: low PLT group (<125×109/L), medium PLT group (126- 225×109/L) and high PLT group (>226×109/L). The mRS was evaluated after three months and one year, respectively, and the difference in long-term prognosis between groups was analyzed. The mRS is an ordered scale coded from 0 (no symptoms at all) through 5 (severe disability) 6 (death). RESULTS: Finally, a total of 99 patients had complete data. The results of the multiple comparisons among the three groups were as follows: the analysis of variance of the mRS at three months after onset yielded F = 6.714 and P = 0.002, and the difference was statistically significant. The mRS was lowest in the medium PLT group (2.09±1.465), and neurological function recovery was the best. After one year, the mRS for the medium PLT group was the lowest (1.49±1.523), with F = 6.860 and P = 0.002. The repeated measures analysis of variance revealed that the effect of continuous rehabilitation was significant in the interval from three months to one year after onset (F = 35.528, P < 0.001). This was very significant, especially for patients taking aspirin (F = 50.908, P < 0.001). However, for patients who did not take aspirin, the effect of continuous rehabilitation was not obvious during the nine months, and the difference between the results of two mRS measurements was not statistically significant (F = 1.089, P = 0.308). CONCLUSIONS: Patients with a PLT count of 126- 225×109/L had the lowest mRS between three months and one year after onset, but had the best recovery of nerve function. Patients who persisted in taking aspirin continued to significantly recover during the 9-month period, from three months to one year after onset. Aspirin is not only a secondary preventive drug, but also an important drug to promote the rehabilitation of CI patients.

Effective Antimicrobial StewaRdship StrategIES (ARIES): Cluster Randomized Trial of Computerized Decision Support System and Prospective Review and Feedback.

BACKGROUND: Prospective review and feedback (PRF) of antibiotic prescriptions and compulsory computerized decision support system (CDSS) are 2 strategies of antimicrobial stewardship. There are limited studies investigating their combined effects. We hypothesized that the use of on-demand (voluntary) CDSS would achieve similar patient outcomes compared with automatically triggered (compulsory) CDSS whenever broad-spectrum antibiotics are ordered. METHODS: A parallel-group, 1:1 block cluster randomized crossover study was conducted in 32 medical and surgical wards from March to August 2017. CDSS use for piperacillin-tazobactam or carbapenem in the intervention clusters was at the demand of the doctor, while in the control clusters CDSS use was compulsory. PRF was continued for both arms. The primary outcome was 30-day mortality. RESULTS: Six hundred forty-one and 616 patients were randomized to voluntary and compulsory CDSS, respectively. There were no differences in 30-day mortality (hazard ratio [HR], 0.87; 95% CI, 0.67-1.12), re-infection and re-admission rates, antibiotic duration, length of stay, or hospitalization cost. The proportion of patients receiving PRF recommendations was not significantly lower in the voluntary CDSS arm (62 [10%] vs 81 [13%]; P = .05). Appropriate indication of antibiotics was high in both arms (351/448 [78%] vs 330/433 [74%]; P = .18). However, in geriatric medicine patients where antibiotic appropriateness was <50%, prescription via compulsory CDSS resulted in a shorter length of stay and lower hospitalization cost. CONCLUSIONS: Voluntary broad-spectrum antibiotics with PRF via CDSS did not result in differing clinical outcomes, antibiotic duration, or length of stay. However, in the setting of low antibiotic appropriateness, compulsory CDSS may be beneficial.

Outcomes of treating AmpC-producing Enterobacterales bacteraemia with carbapenems vs. non-carbapenems.

INTRODUCTION: AmpC ß-lactamases are found in Enterobacter species, Serratia species, Citrobacter freundii, Providencia species and Morganella morganii ('ESCPM'). Carbapenems are commonly used to treat severe 'ESCPM' infections. Carbapenem-sparing agents are needed because of increasing carbapenem resistance worldwide. Use of cefepime and piperacillin-tazobactam has limited supportive clinical data. We evaluated the efficacy of non-carbapenems vs. carbapenems in 'ESCPM' bacteraemia. METHODS: A retrospective cohort study was conducted on patients with 'ESCPM' bacteraemia. Primary outcome was 30-day mortality. Analyses were performed on patients who received carbapenems vs. piperacillin-tazobactam or cefepime monotherapy as empirical and definitive therapy. Propensity score for carbapenem therapy was adjusted for in multivariate analyses for 30-day mortality. RESULTS: A total of 241 patients were included. The most common bacterium isolated was Enterobacter species (58.1%). Common sources were urinary (22.8%) and vascular lines (22.0%). Carbapenems (28.6%) and piperacillin-tazobactam (28.6%) were the commonest empirical antibiotics. Carbapenems (54.8%) and cefepime (23.7%) were the most common definitive antibiotics. Median Pitt bacteraemia score was 1 (interquartile range [IQR], 0-2). Overall, 30-day mortality was 12.9%. Adjusted multivariate analyses for empirical and definitive antibiotic treatment models yielded risk factors for 30-day mortality, including higher Pitt bacteraemia score (empirical: adjusted OR [aOR] 1.21 for each point increase, 95% confidence interval [CI]:1.01-1.45; definitive: aOR 1.33 for each point increase, 95% CI:1.06-1.69) and age (empirical: aOR 1.04 for each year increase, 95% CI:1.01-1.08). Empirical piperacillin-tazobactam (aOR 0.29, 95% CI:0.07-1.27) and definitive cefepime (aOR 0.65, 95% CI:0.12-3.55) were not associated with 30-day mortality. CONCLUSIONS: Compared with carbapenem therapy, empirical piperacillin-tazobactam and definitive cefepime were not associated with 30-day mortality in 'ESCPM' bacteraemia.

Target screening and antihyperglycemic activity on SGLT2 and α-glucosidase in vitro and in vivo of TSG from Polygonum multiflorum / 中草药

Objective: To study the mechanism that TSG can reduce plasma glucose level by inhibiting sodium-dependent glucose cotransporters 2 (SGLT2) and α-glucosidase in vitro and in vivo. Methods: Molecular docking method was used to study the binding affinities of TSG and diabetes related targets. The structures of targets were taken from Protein Data Bank or references. 1-NBDG and PNPG were used as the substrates for the inhibition assays of TSG against SGLT2 and α-glucosidase respectively in vitro. The antihyperglycemic activity of TSG was operated by oral glucose tolerance test (OGTT) and urinary glucose excretion (UGE) test in rats. Results: TSG was identified as the inhibitors of SGLT2 with the docking score of -9.35 less than -9.79 of dapagliflozin as the positive control and α-glucosidase with the docking score of -5.44 compared to -5.58 of acarbose as the positive control. TSG showed the inhibitory rate of 21.6% at the dose of 10 μmol/L against SGLT2 and 32.5% at the dose of 100 μmol/L in vitro test. Compared with model group, the group of 120 mg/kg dose had significant difference (P < 0.05) but the overall effect was not as strong as dapagliflozin in OGTT and UGE test. The result of rat in vivo test showed that glucose inhibition rate of TSG (120 mg/kg) was (9.3 ± 1.0)%, urinary glucose content was (435.5 ± 84.0) mg/kg, which showed certain hypoglycemic effect. Conclusion: TSG exhibited antiglycemic activity through inhibiting SGLT2 and α-glucosidase, which was considered to be a new lead compound of dual target inhibitors.

No association between resistance mutations, empiric antibiotic, and mortality in ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae bacteremia.

The objective of this study was to correlate resistance mutations of extended spectrum beta-lactamases (ESBL) and AmpC beta-lactamases and virulence factors (VF) with 30-day mortality in patients treated with either piperacillin-tazobactam or carbapenems. A post-hoc analysis on 123 patients with ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae bacteremia treated empirically with piperacillin-tazobactam and carbapenems was performed. Beta-lactamase resistance mutations and VF were identified by whole genome sequencing (WGS). The primary endpoint was 30-day mortality. Multivariate analyses were performed using logistic regression. WGS showed diverse multilocus sequence types (MLST) in 43 K. pneumoniae strains, while ST131 predominated in E. coli strains (57/80). CTX-M was most commonly detected (76/80 [95%] of E. coli; 39/43 [91%] of K pneumoniae.), followed by OXA (53/80 [66%] of E. coli; 34/43 [79%] of K. pneumoniae). A significant correlation was found between the number of genes encoding third-generation cephalosporin-resistant beta-lactamases and 30-day mortality (p = 0.045). The positive association was not significant after controlling for empiric carbapenem, Pitt score 3 and K. pneumoniae (OR 2.43, P = 0.073). None of the VF was associated with 30-day mortality. No association was found between 30-day mortality and any ESBL and AmpC beta-lactamases or VF when piperacillin-tazobactam or carbapenems were given. No significant association between 30-day mortality and active empiric therapy was found.

CP-25 Attenuates the Activation of CD4+ T Cells Stimulated with Immunoglobulin D in Human.

Researchers have shown that the level of immunoglobulin D (IgD) is often elevated in patients with autoimmune diseases. The possible roles of IgD on the function of human T cell activation are still unclear. Paeoniflorin-6'-O-benzene sulfonate (code: CP-25), the chemistry structural modifications of paeoniflorin, was a novel drug of anti-inflammation and immunomodulation. The aims of this study were to determine if human CD4+ T cells could be activated by IgD via the IgD receptor (IgDR)-Lck pathway and whether the novel compound CP-25 could affect the activation of T cells by regulating Lck. Human CD4+ T cells were purified from peripheral blood mononuclear cells using microbeads. T cell viability and proliferation were detected by Cell Counting Kit-8 and CFSE Cell Proliferation Kit. Cytokines secreted by T cells were assessed with the Quantibody Human Inflammation Array. The binding affinity and expression of IgDR on T cells were detected by flow cytometry, and protein expression of IgDR, Lck, and P-Lck were analyzed by western blot. IgD was shown to bind to IgDR on CD4+ T cells in a concentration-dependent manner and stimulate the activation and proliferation of these cells by enhancing phosphorylation of the activating tyrosine residue of Lck (Tyr394). CP-25 inhibited the IgD-stimulated activation and proliferation of CD4+ T cells, as well as the production of inflammatory cytokines; it was thus suggested that this process might be related to the downregulation of Lck (Tyr394) phosphorylation. These results demonstrate that IgD amplifies the activation of CD4+ T cells, which could be mediated by Lck phosphorylation. Further, CP-25, via its ability to modulate Lck, is a novel potential therapeutic agent for the treatment of human autoimmune diseases.

The current state of autologous fat graft / 中华整形外科杂志

Autologous fat grafting has been widely used in plastic and cosmetic surgery, however, the unpredictable survival rate has plagued many surgeons.The fat grafting includes the harvesting, purification and injection, different methods have a certain impacton the survival of the fat.The following review provides a brief summary on the current status of autologous fat grafting.

Key points of high SMAS facelift / 中华整形外科杂志

Objective@#To summarize the key points of high SMAS facelift.@*Methods@#Forty-six patients who had received high SMAS facelift were included in this study. All the patients had subcutaneous dissection by classic facelift incision. The temporal region dissection was performed superficial to middle temporal fascia to avoid temporal branches injury. The zygomatic ligaments were released by sharp and blunt dissection at malar prominence and zygomatic arch. After sub-SMAS dissection, a complete SMAS-platysma flap was raised including temporal, malar, lower face, neck, and one third or half of the midface.@*Results@#Forty patients had postoprative follow-up for more than one year. Twenty patients showed " excellent" results, eighteen patients had " good" results , two patients " common" . The good and excellent rate was 95%.@*Conclusions@#The key points of high SMAS facelift to achieve ideal outcome depend on the safe dissection of superficial temporal fascia and the release of zygomatic ligaments.