Abstract

Abstract Background Critically ill patients have altered pharmacokinetic (PK) due to severity of illness and multi-organ failure. The lack of pharmacokinetic and pharmacodynamic data in Continuous Sustained Low-efficiency Dialysis (C-SLED) further perpetuates the uncertainty of efficacy with current antimicrobial dosing strategies. The objective of this study is to evaluate patient-specific PK of various β-lactams antibiotics in critically ill patients on C-SLED to assess if the current dosing strategy leads to therapeutic drug levels. Methods This prospective observational cohort study was performed at an academic medical center from November 2021 to June 2022. It included patients age > 18 years and on β-lactam antibiotics while on C-SLED. Therapeutic drug monitoring (TDM) was performed by checking two levels (peak and trough). These levels were used to calculate patient-specific elimination rate constant (k), half-life, and the fraction of time above MIC (fT>MIC). Other data collected included demographics, β-lactam regimens, source of infection, microbiology data, mortality on days 7 and 30, and length of stay. Descriptive statistics were used for data analysis. Results There were 11 patients included in the study with a median age of 55 and 82% (n = 9) of patients were male. β-lactam daily regimen was dosed as creatinine clearance (CrCl) > 50mL/min in 71.4% of patients (n = 10), CrCl 30-50 mL/min in 28.5% (n = 4), and < 30mL/min in 0% of patients. An extended infusion dosing strategy was used in 35.6% of patients (n = 5). The therapeutic drug target (50%fT > MIC for penicillins, 60%fT > MIC for cephalosporins, 40%fT > MIC for carbapenems) was achieved in 100% (n=14) of patients. Dose adjustment was not needed in all 14 cases. However, 100%fT > MIC was only achieved in 64% (n=9) patients. The median hospital length of stay was 60 days. Mortality on days 7 and 30 was 9% (n=1) and 27% (n=3), respectively. Conclusion Preliminary analysis shows that β-lactam daily dose based on CrCl of >30mL/min leads to therapeutic drug levels in patients on C-SLED. Disclosures All Authors: No reported disclosures.

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