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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 : : Acetaminophen is commonly used for the relief of pain and fever. Advocacy organizations recommend acetaminophen as the drug of choice in patients with kidney disease. Although some studies have suggested a risk of renal impairment after the use of acetaminophen, the effect of acetaminophen on the risk of renal impairment is unclear. The purpose of this research was to demonstrate any correlation linking acetaminophen treatment and renal impairment. Methods : : We performed a systematic review and meta-analysis of the association between acetaminophen and renal impairment in adults by searching Cochrane Library, PubMed, and Embase databases from initiation to June 16, 2019. Results : : Of 13,097 articles identified, 5 studies (2 cohort studies and 3 case-control studies) with a total of 13,114 participants were included. In the random-effects meta-analysis of the cohort study, acetaminophen use was shown to have statistically significant effects on the increased risk of renal impairment (adjusted odds ratio 1.23; 95% confidence interval, 1.07-1.40). The results of sensitivity and subgroup analyses also suggested that acetaminophen use increases the risk of renal impairment. The Egger’s test (P = 0.607) and Begg’s test (P = 0.732) revealed no apparent publication bias. Conclusion : : Acetaminophen is associated with a significantly increased risk of newly developing renal impairment in adults. Physicians who prescribe acetaminophen should be aware of potential adverse renal effects. A longitudinal study that further explores this association is warranted.

What is known and objective Hyponatremia is a common side effect of thiazide diuretics that can lead to increased mortality and hospitalization. A rapid and accurate screening tool is needed for rapid and appropriate management. In this study, we report on the development of a simple clinical screening tool for hyponatremia using thiazide diuretics. Methods This nested case-control study was performed by collecting data from 1 January 2015 to 30 June 2017. Univariable and multivariable logistic regressions were used to identify potential risk factors. The regression coefficients were converted into item scores by dividing each regression coefficient with the minimum coefficient in the model and rounding to the nearest integer. This value was then summed to the total score. The prediction power of the model was determined by the area under the receiver operating characteristic curve (AuROC). Results and discussion Six clinical risk factors, namely age ≥65 years, benzodiazepine use, history of a cerebrovascular accident, dose of hydrochlorothiazide ≥25 mg, female sex and statin use, were included in our ABCDF-S score. The model showed good power of prediction (AuROC 81.53%, 95% confidence interval [CI]: 78%-84%) and good calibration (Hosmer-Lemeshow X2 = 23.20; P = .39). The positive likelihood ratios of hyponatremia in patients with low risk (score ≤ 6) and high risk (score ≥ 8) were 0.26 (95% CI: 0.21-0.32) and 3.89 (95% CI: 3.11-4.86), respectively. What is new and conclusion The screening tool with six risk predictors provided a useful prediction index for thiazide-associated hyponatremia. However, further validation of the tool is warranted prior to its utilization in routine clinical practice.