A prospective cohort study on the relationship between vancomycin steady-state trough concentration and efficacy and safety in Chinese adults

Clinical guidelines recommend a steady-state vancomycin(VCM)trough concentration(SVTC)of 10–15 mg/L for regular infections and 15–20 mg/L for severe infections.However,clinical trials have shown that increasing SVTC is not beneficial for efficacy,and instead it leads to nephrotoxicity.To verify whether increasing the SVTC results in improved clinical outcomes with sustainable adverse effects,we prospectively determined its correlation with clinical efficacy and safety.The participants included patients hospitalized with Gram-positive bacterial infections from March 2017 through October 2018.The patients were classified into group I(SVTC<10 mg/L),II(10≤SVTC≤20 mg/L),or III(SVTC>20 mg/L).Clinical,microbiological,and laboratory data were collected.Clinical outcomes between group I and II were matched after propensity score matching(PSM).A total of 331 patients were included in this study.Clinical failure occurred in 59(29%)of 204 patients on day 14,with no significant difference between groups I and II(P=0.535).Infection recurred at 28 d in 62(30%)of 204 patients,and no significant difference in infection recurrence was observed between both the groups(log-rank,P=0.674).Except for a significant increase in the incidence of acute kidney injury in group II,no significant difference was observed between two groups for any clinical results.The incidence of adverse events in groups I and II was significantly lower than that in group III(P<0.001).SVTC had an applicable cut-off point at 14.55 mg/L.SVTC was not correlated with VCM clinical efficacy,while it was a good indicator of nephrotoxicity.

Population pharmacokinetics of vancomycin in Chinese elderly patients and its application for dose individualisation

In the present study, we aimed to develop a population pharmacokinetics(PPK) model of vancomycin(VCM) and propose the individualised dosage regimen for Chinese elderly patients. The data were collected prospectively from Chinese elderly patients receiving VCM therapy. Steady-state trough concentrations of VCM were determined using an enzyme-multiplied immunoassay. Patients’ sex, age, body weight, concomitant medications, infection type, and laboratory findings were recorded. The PPK model was developed using nonlinear mixed-effects model software. Moreover, we used Monte Carlo simulations to develop an initial dosage regimen targeting various VCM through concentration ranges based on the final model. We found that VCM clearance(CL) was significantly influenced by post-craniotomy meningitis(PCM) and glomerular filtration rate in elderly patients. Additionally, a new dosage regimen was proposed to individualise VCM regimen for PCM and non-PCM elderly patients. A PPK model was established to estimate the individual VCM CL for elderly patients, which could be applied for individualising doses in the target population.