Background: Vancomycin is frequently monitored, but target levels for continuous infusion of vancomycin (CIV) are based on expert opinion. Rarely have vancomycin concentrations been correlated with therapeutic efficacy or safety of CIV. Objectives: Associations between vancomycin steady-state serum concentrations and treatment failure or toxicity with CIV were examined. Methods: A retrospective, single centre cohort study was conducted of consecutive critically ill surgical patients receiving CIV between 2010-2022. After detecting associations between vancomycin levels, renal function and health status, four subgroups were defined based on estimated glomerular filtration rate (</>=90mL/min/1.73m2) and Simplified Acute Physiology Score (SAPS) II (<=/>36). Failure and toxicity of vancomycin serum concentrations were assessed using primary (mortality, acute kidney injury (AKI)) and secondary (clinical and microbiological failure) endpoints. Predictors of outcome parameters were identified using logistic and Cox regression. Concentrations were compared by bivariate comparisons, post-hoc tests following analysis of variance for the regression models and desirability of outcome ranking. Concentration cut-offs were determined by receiver operating characteristic and classification and regression tree analyses. Results: 922 patients were included. Higher vancomycin concentrations (first 72h average; specifically >25mg/L) were associated with higher mortality, AKI and clinical failure, but less microbiological failure. For SAPS>36, concentrations <20mg/L (i.e. 15-20mg/L or <17mg/L) correlated with the best treatment outcome, for SAPS<=36 concentrations >19mg/L (i.e. 20-25mg/L or 19-28mg/L). Conclusion: Retrospective analyses of vancomycin serum concentrations during CIV suggest that ICU patients' disease severity should be considered when selecting a target concentration. The target concentration might be sought inversely related to SAPS, which should be confirmed in future prospective controlled trials.

The authors have declared no competing interest.

This study did not receive any funding.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted in accordance with the Declaration of Helsinki (2013 version) and was approved by the Ethics Committee of the University of Witten Herdecke, Germany, with a waiver of the need for patients' informed consent (Chair: Prof. Dr. med. P.W. Gaidzik, No. S 55/2022).

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All data produced in the present study are available upon reasonable request to the authors.