A Prospective Cohort Study On Vancomycin Steady-State Trough Concentration Distribution In Chinese Adults And The Relationship Between Concentration And Both Clinical Efficacy And Safety

ObjectivesIn order to verify whether 10-20 mg/L is the optimal concentration in Chinese adults,we prospectively explored the distribution of steady-state serum vancomycin trough concentration?SSVTC?and assessed the correlation between SSVTC and clinical efficacy and safety.We also devoted to identify patient characteristic factors,if any,that are associated with SSVTC.We aimed to explore the distribution of SSVTC and assessed the correlation between SSVTC and clinical safety and efficacy.MethodsA prospective,open,single-centre cohort study include patients with gram-positive bacterial infections hospitalized form March 2017 through October 2018.The adult patients??18 years?with Clearance creatinine?CLcr??50ml/min who would be treated per 12 hours with 1000mg vancomycin infused intravenously over one hour.Serum sample would be collected 30min before vancomycin was administered for at least the fifth maintenance doses.the SSVTC was measured via enzyme-multiplied immunoassay technique?EMIT?.According to the initial level of SSVTC,patients were stratified into 3 groups:group?(C_min<10mg/L),group?(10mg/L?C_min?20mg/L)and group?(C_min>20mg/L).The primary outcome was clinical failure at 14 days.The secondary outcome included 28-day recurrence of infection.Factors influencing SSVTC were also determined by using multiple logistic regression analysis.In order to obtain95%confidence interval,multivariate analyses were performed using ordinal logistic regression as appropriate.We constructed both a logistic regression model to calculate a propensity score?PS?and Kaplan-Meier survival analysis for efficacy evaluation.ResultsIn all,331 patients were included.SSVTC of<10mg/L were frequently observed?136/331,41%?.Clinical success at day 14 occurred in 145?71%?of 204 patients,with no significant differences between group?and group??P=0.440?.The 28-day recurrence of infection was 62?30%?of 204 patients,and similar in the two groups.No significant difference were observed between two groups for all outcomes,except for increased the incidence of acute kidney injury?AKI?with high level of SSVTC.The logistic regression analysis indicates SSVTC has no statistical correlation with clinical outcomes.Multivariate analysis revealed age,weight,Scr,serious infection and hypertension were associated with the level of SSVTC.The occurrence of adverse event both in group?and group?exhibited a significant lower value,compared with group??P<0.001?.The 14.55 mg/L cut point indicates 70%sensitivity and 78%specificity on vancomycin-related nephrotoxic adverse effects.?OR=0.82,95%CI=0.72-0.83?ConclusionsSSVTC has no statistical correlation with clinical efficacy,However,it is an good indicator of nephrotoxicity in therapeutic drug monitoring of vancomycin.