Prediction of Unbound Vancomycin Levels in Intensive Care Unit and Nonintensive Care Unit Patients: Total Bilirubin May Play an Important Role

Abstract

Background The mean unbound vancomycin fraction and whether the unbound vancomycin level could be predicted from the total vancomycin level are still controversial, especially for patients in different groups, such as intensive care unit (ICU) versus non-ICU patients. Other relevant potential patient characteristics that may predict unbound vancomycin levels have yet to be clearly determined. Methods We enrolled a relatively large study population and included widely comprehensive potential covariates to evaluate the unbound vancomycin fractions in a cohort of ICU (n=117 samples) and non-ICU patients (n=73 samples) by using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results The mean unbound vancomycin fraction was 45.80% ± 18.69% (median, 46.01%; range: 2.13–99.45%) in the samples from the total population. No significant differences in the unbound vancomycin fraction were found between the ICU patients and the non-ICU patients (P=0.359). A significant correlation was established between the unbound and total vancomycin levels. The unbound vancomycin level can be predicted with the following equations: unbound vancomycin level=0.395×total vancomycin level+0.019×total bilirubin level+0.468 (R 2 =0.771) for the ICU patients and unbound vancomycin level=0.526×total vancomycin level-0.527 (R 2 =0.749) for the non-ICU patients. Overall, the observed-versus-predicted plots were acceptable. Conclusion A significant correlation between the total and unbound vancomycin levels was found, and measurement of the unbound vancomycin level seems to have no added value over measurement of the total vancomycin level. The study developed parsimonious equations for predicting the unbound vancomycin level and provides a reference for clinicians to predict the unbound vancomycin level in adult populations.

Age-Related Changes in Vancomycin Protein Binding: Is It Time to Take It Seriously?

“…The mean unbound fraction between the 3 groups was 47% (range: 41%-60%), which is close to the assumed free fraction of 50%. This finding is also supported by Li et al, 12 who reported a significant correlation between total and free VAN concentrations in ICU and non-ICU patient populations. The free VAN concentration seemed to have no added value over the measurement of total VAN concentration.…”

“…In adult patients in ICU, supported by ECMO or in a renal dialysis ward, only a small difference was found between the model-EFVC and AFVC 11,12 : mean 6 SD difference = 21.0 6 0.72 mg/L, 20.77 6 0.77 mg/L, and 0.18 6 0.52 mg/L, respectively. Furthermore, a similar number of model-EFVCs and AFVCs were within the free VAN therapeutic range: 54.5% versus 54.5%, 52.7% versus 52.7%, and 60.4% versus 64.2%, respectively (Fig.…”

“…A literature review was conducted using Embase (search terms: VAN, free, unbound, year range 1996–2023) to identify models developed to estimate free (unbound) concentrations from the total VAN concentrations in adults, children, and neonates. A literature search identified 5 recent studies that investigated free VAN concentrations (separated by ultrafiltration) and their relationship with total concentrations: Butterfield et al 11 and Li et al 12 in adults, Oyaert et al 7 in adults and children, De Cock et al 8 in children, and Smits et al 9 in neonates. The correlation between the free and total VAN concentrations was investigated using multivariate regression analysis.…”

“…In all studies, the most important predictor of free VAN concentration was total VAN concentration. Other covariates in the adult models included bilirubin, 12 albumin, immunoglobulin A (IgA), 7 total protein, and the dialysis status. 11 Considering that IgA concentrations were not routinely measured at the authors' institution, it was not possible to implement the adult model of Oyaert et al 7 In the pediatric models, albumin 7,9 and total protein 8 were influential.…”