No one-size-fits-all approach: Retrospective analysis of efficacy and safety of serum concentrations of continuously administered vancomycin in critically ill adults reveals different target serum concentrations depending on disease severity

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.

Associations between vancomycin steady-state serum concentrations and treatment failure or toxicity with CIV were examined.

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 (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.

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 19mg/L (i.e. 20-25mg/L or 19-28mg/L).

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. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study did not receive any funding. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes 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). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes viertelk{at}kliniken-koeln.de, carmen.meegen{at}tu-dortmund.de, swetlana.herbrandt{at}tu-dortmund.de, annecket{at}kliniken-koeln.de, mattnerf{at}kliniken-koeln.de Data Availability All data produced in the present study are available upon reasonable request to the authors.