Study On Vancomycin Population Pharmacokinetics And Clinical Efficacy In Neurosurgical Adult

Objective:(1)To compare the capability of Serum cystatin C(Cystatin C,Cys C)and Serum creatinine(SCR)that describe the characteristic of vancomycin population pharmacokinetics in neurosurgical adult patients based on population pharmacokinetic modeling;(2)To find the factors that may affect treatment out-comes in post-craniotomy patients with confirmed or suspected meningitis and evaluate the correlations between pharmacokinetic/phrmacodynamic(PK/PD)in-dices and the clinical efficacy of vancomycin based on the model established in part 1.Methods:(1)The patients from Neurosurgery Department,age ≥ 8 and hav-ing a steady-state plasma trough concentration at least were collected retrospec-tively.First,a population pharmacokinetic model(Cys C model)was established used Glomerular filtration rate estimated from Cys C(cGRF);Then,another model was established used same patients datas,but the Glomerular filtration rate estimated from SCR(sGRF).The predictive proformance of the two models were evaluated by Normalized Prediction Distribution Error(NPDE),goodness of fit plots,average prediction error and average absolute prediction error and so on.The aim of this study was to finding out one better model through comparing the predictive performance of these two models.(2)The adult patients with post-cra-niotomy meningitis that confirmed or suspected caused by the Gram-positive bac-terial were collected retrospectively.The clinical outcome was judged according to the patients’microbial culture results,infection index,clinical symptoms and medical image and so on.Then,the patients were devided into two groups based on different clinical outcomes.Univariate and multivariate logistic regression analysis were performed to identify the risk factors of treatment outcome of van-comycin.Results:(1)Two one-compartment models with first-order elimination were established based on Cys C and SCR,respectively.The predictive performance of these two models are similar when compare each other through Normalized Pre-diction Distribution Error(NPDE),goodness of fit plots,average prediction error and average absolute prediction error and so on.The formulas of two models were shown as follow:SCR model:CL(L/h)=[6.46×(GFR/118)0.474×(AGE/47)0.206]×e0.045;V(L)=60.1(L)Cys C model:CL(L/h)=[6.4×(GFR/128)0.515×(BW/60)0.417×(AGE/47)0.267]×e0.0417;V(L)=62(L)(2)There are 113 patients met the criterias and were enrolled in this study,there were 88 patients had a successful treatment outcome,and others 25 patients had a failure treatment outcome.The AUC0-24/MIC(AUMIC)value(p=0.657)and steady-state average concentrations(p=0.161)weren’t significant difference be-tween success group and failure group.Multivariate logistic regression analysis results shown that Cerebrospinal fluid glucose(OR,1.47;95%CI,1.09-2.00,p=0.01)was significant difference between success group and failure group.Conclusions:(1)The predictive performance of SCR final model and Cys C final model are similar,both of them can be used to assist clinicians in individ-ual administering vancomycin.(2)In this study,we were not find that steady-state average trough concentration was associated with clinical outcome.But we found cerebrospinal fluid glucose concentration in failure group was less than those in success group.