Impact of Obesity on Serum Concentrations of Vancomycin Administered as Continuous Infusion and on Clinical Outcomes in Critically Ill Patients-A Retrospective Observational Study.

Abstract

Background/Objectives: Vancomycin is a commonly used antibiotic in critically ill patients with severe methicillin-resistant Staphylococcus aureus infections. Due to its narrow therapeutic window, under- or overdosing is likely to result in adverse effects, especially in patients with conditions associated with altered pharmacokinetics such as obesity. The objective of this study was to investigate the impact of obesity on serum concentrations of vancomycin in critically ill patients receiving intravenous vancomycin by continuous infusion based on ideal body weight (IBW). Methods: This retrospective observational study performed at the University Hospital of Leipzig, Germany, included all patients admitted to the intensive care unit (ICU) between January 2009 and December 2015 who received guideline-based vancomycin therapy based on IBW. Serum concentrations were obtained through routinely performed therapeutic drug monitoring (TDM). Results: A total of 1066 patients with a median age of 62 years were included in this study. The median (25%; 75% quantile) vancomycin treatment duration was 4 (2; 7) days and the median time to reach target concentrations of 20-25 mg L^-1 was 3 (2; 4) days without a significant difference between BMI groups. Overall, only 25.9% of patients were in the therapeutic range of 20-25 mg L^-1 in the entire treatment interval. 47.8% of vancomycin concentrations obtained from TDM were below the desired target range with no differences between the BMI groups (p = 0.077). 26.3% of measurements exceeded the target range, with a significant increase in the morbidly obese group (p < 0.001). A higher BMI was associated with an increased ICU, in-hospital, 28- and 90-day mortality in morbidly obese patients (p < 0.05). Age, BMI and high SAPS-II and SOFA scores were significant predictors of an increased risk of death. Conclusions: Our preliminary findings suggest that IBW-based dosing may help reduce the risk of supratherapeutic concentrations in morbidly obese patients. The high rates of sub- and supratherapeutic vancomycin serum concentrations across all patients highlight the need for close TDM and dose adjustments, particularly in morbidly obese patients with the highest rates of supratherapeutic vancomycin serum concentrations and of RRT.