Background: Patients who had mechanical heart valves and an international normalized ratio (INR) of >5.0 should be managed by temporary cessation of vitamin K antagonist. This study aimed to investigate the safety of low-dose vitamin K1 in patients with mechanical heart valves who have supratherapeutic INR.Methods: CINAHL, Cochran Library, Clinical trial.gov, OpenGrey, PubMed, ScienceDirect, and Scopus were systematically searched from the inception up to October 2021 without language restriction. Studies comparing the safety of low-dose vitamin K1 treatment in patients with placebo or other anticoagulant reversal agents were included. We used a random-effect model for the meta-analysis. Publication bias was determined by a funnel plot with subsequent Begg's test and Egger's test.Results: From 7529 retrieved studies, 3 randomized control trials were included in the meta-analysis. Pooled data demonstrated that low-dose vitamin K was not associated with thromboembolism rate (risk ratio [RR] = 0.94; 95% CI: 0.19-4.55) major bleeding rate (RR = 0.58; 95% CI: 0.07-4.82), and minor bleeding rate (RR = 0.60; 95% CI: 0.07-5.09). Subgroup and sensitivity analysis demonstrated the nonsignificant effect of low-dose vitamin K on the risk of thromboembolism. Publication bias was not apparent, according to Begg's test and Egger's test (P = .090 and 0.134, respectively). Conclusion:The current evidence does not support the role of low-dose vitamin K as a trigger of thromboembolism in supratherapeutic INR patients with mechanical heart valves. Nevertheless, more well-designed studies with larger sample sizes are required to justify this research question.

Background: Septic shock is a serious condition leading to increased mortality. Despite previous report of no benefit, thiamine has emerged as potential therapy to reduce mortality in septic shock patients. This study aimed to investigate the effect of thiamine in mortality rate in patients with septic shock. Methods: Eight databases, including MEDLINE, EMBASE, Science Direct, Scopus, Cochrane, CINAHL, Open Grey, and Dart-Europe, were systematically searched from the inception of the database up to August 21, 2020. Studies evaluating the effectiveness of thiamine on mortality rate in septic shock patients compared between thiamine and placebo were included. We used random-effects model to analyze the mortality with risk ratio (RR) and 95% confidence interval (95% CI). The subgroup and sensitivity analysis were performed to examine the influence of variables. Publication bias was considered using funnel plot, Begg's test, and Egger's test. Results: A total of 3,658 studies were retrieved and reviewed. Five studies were included for meta-analysis. In random-effects meta-analysis of the randomized controlled trials, although not statistically significant, there was a trend which suggested that thiamine may reduce mortality rate in septic shock patients (RR, 0.96; 95% CI: 0.72–1.28, P = 0.774). The result of sensitivity and subgroup analyses also supported the suggestion that thiamine may decrease mortality in septic shock patients. The Begg's test ( P = 0.624) and Egger's test ( P = 0.777) revealed no publication bias. Conclusions: Although not statistically significant, thiamine may reduce mortality rate in septic shock patients. Further prospective studies with larger sample size are warranted.

Background To predict the appropriate dosing of intravenous fosfomycin for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infection in continuous renal replacement therapy (CRRT) patients. Methods Minimum inhibitory concentration (MIC) values of all isolates were determined by E-test method. Population pharmacokinetic parameters were obtained from a previously published study. The percentages of a 24-hour period in which the drug concentration exceeded the MIC (%T >MIC) were defined to be 70% T >MIC and 100% T >MIC, respectively. In addition, the 24-hour area under the unbound concentration-time curve over the MIC (AUC0-24/MIC) of 45 mg·h/L was used as a target value. All dosing regimens were estimated for the probability of target attainment (PTA) using a Monte Carlo simulation. Results For the effluent rate of 20 mL/kg/h, the PTA for reaching 70% T >MIC, 100% T >MIC, and AUC0-24/MIC of 45 mg·h/L was achieved in pathogens with a MIC of 24 mg/L, 12 mg/L, and 24 mg/L in all regimens, respectively. Meanwhile for the effluent rate of 25 mL/kg/h, the PTA for reaching 70% T >MIC, 100% T >MIC, and AUC0-24/MIC of 45 mg·h/L was achieved in organisms with a MIC of 16 mg/L, 12 mg/L and 24 mg/L in all regimens, respectively. Conclusion The appropriate fosfomycin dosing regimens for CRE infections in critically ill patients receiving CRRT were suggested based on pharmacokinetic/pharmacodynamic targets, MIC values, and effluent rates. Clinical validation is warranted. Disclosures All Authors: No reported disclosures.

Background: Mortality from multidrug-resistant (MDR) pathogens is an urgent healthcare crisis worldwide. At present we do not have any simplified screening tools to predict the risk of mortality associated with MDR infections. The aim of this study was to develop a screening tool to predict mortality in patients with multidrug-resistant organisms.Methods: A retrospective cohort study to evaluate mortality risks in patients with MDR infections was conducted at Phrae Hospital. Univariable and multivariable analyses were used to classify possible risk factors. The model performance was internally validated utilizing the mean of three measures of discrimination corrected by the optimism using a 1000-bootstrap procedure. The coefficients were transformed into item scores by dividing each coefficient with the lowest coefficient and then rounding to the most adjacent number. The area under the receiver operating characteristic curve (AuROC) was used to determine the performance of the model.Results: Between 1 October 2018 and 30 September 2020, a total of 504 patients with MDR infections were enrolled. The ICU-SEPSA score composed of eight clinical risk factors: 1) immunocompromised host, 2) chronic obstructive pulmonary disease, 3) urinary tract infection, 4) sepsis, 5) placement of endotracheal tube, 6) pneumonia, 7) septic shock, and 8) use of antibiotics within the past 3 months. The model showed good calibration (Hosmer-Lemeshow χ2 = 19.27; p-value = 0.50) and good discrimination after optimism correction (AuROC 84.6%, 95% confidence interval [Cl]: 81.0%–88.0%). The positive likelihood ratio of low risk (score ≤ 5) and high risk (score ≥ 8) were 2.07 (95% CI: 1.74–2.46) and 12.35 (95% CI: 4.90–31.13), respectively.Conclusion: A simplified predictive scoring tool wad developed to predict mortality in patients with MDR infections. Due to a single-study design of this study, external validation of the results before applying in other clinical practice settings is warranted.