Determination Of Teicoplanin Plasma Concentration And Clinical Application In Critically Ill Patients By HPLC

Objective:The aim of this study is to establish a high performance liquid chromatography?HPLC?for the determination of teicoplanin in human plasma,to do the therapeutic drug monitoring?TDM?for critically ill patients who are infected by Gram-positive bacteria and treated by teicoplanin,to analyze the teicoplanin pharmacokinetics?PK?characteristics in critically ill patients,to explore the related factors affecting the teicoplain trough teicoplanin?C₀?by multiple stepwise regression analysis,to evaluate the effectiveness and safety of Gram-positive bacteria infection treatment of teicoplanin by the recorded symptoms,bacterial culture,laboratory tests and the adverse reactions that may be associated with teicoplanin during the patients'administration,to operate a different-dose-teicoplanin controlled study in critically ill patients in order to observe the effect of dose on blood drug concentration and efficacy and better assist in the formulation of clinical decision-making.Method:1.Determination of teicoplanin in human plasma by HPLC:internal standard method and external standard method:Waters System-C₁₈ column?250mm*4.6 mm,5?m,Waters?;mobile phase:0.01 mol/L sodium dihydrogen phosphate buffer?pH2.53?:acetonitrile?75:25,V/V?;flow rate:1.2 mL/min;ultraviolet detection wavelength:215 nm.2.The teicoplanin therapeutic drug monitoring and the influencing factors analysis in critically ill patients:prospectively recruiting 58 patients with Gram-positive bacterial infections were treated with teicoplanin in accordance with the criteria of inclusion and exclusion from July 2017 to January 2019.All patients were collected for a blood sample before the administration of the teicoplanin on the fourth day of therapy.Plasma samples were collected by centrifugation and stored at-20?for examination.The plasma concentration of teicoplanin was determined by HPLC.SPSS 25.0 was used to analyze the PK characteristics of teicoplanin in critically ill patients.Multivariate stepwise regression analysis was conducted with C₀ as dependent variable,white blood cell?WBC?,percentage of neutrophils?Neu?,serum creatinine?Cr?,and hypersensitive C-reactive protein?hs-CRP?as independent variables to investigate the related factors of C₀ in critically ill patients.3.TDM and analysis of different doses of teicoplanin in the treatment of critically ill hematological patients:prospectively recruited patients with severe diseases who were treated with teicoplanin for Gram-positive bacterial infections and TDM in strict accordance with the inclusion and exclusion criteria from October 2017 to January2019.The loading dosage regimen of the experimental group was required to be 600mg,q12h,3 doses and the maintaining dose of 600 mg,qd;meanwhile the loading dosage regimen of the control group was 400 mg,q12h,3 doses,and the maintaining dose of 400 mg,qd.All patients were collected for a blood sample before the administration of the teicoplanin on the fourth day of therapy.The plasma teicoplanin concentration,efficacy and safety of the two groups were compared.Results:1.Determination of teicoplanin in human plasma by HPLC:The linear range of internal and external standard methods established in this study is 3.125-100 mg/L,and the lower limit of quantification is 3.125 mg/L.The precision RSD of plasma samples in day and day is less than 6.44%,the absolute recovery is between 90%and 96%,and RSD is 1.42%.2.The teicoplanin therapeutic drug monitoring and the of influencing factors analysis in critically ill patients:58 patients?39 males and 19 females?were enrolled strictly according to the criteria of admission and discharge.The determination range of C₀ was 0-22.6 mg/L,and the median trough concentration was 8.90?5.90,10.75?mg/L.According to the reference value in the National Prescription Collection Analysis of China,the valid trough concentration of teicoplanin in blood samples ranged from10 mg/L to 25 mg/L.The distribution of 58 monitoring results in three concentration ranges<10 mg/L,10-15 mg/L and>15 mg/L were 32,22 and 4 cases respectively,accounting for 55.2%,37.9%and 6.9%of the total monitoring results.Multivariate stepwise regression analysis showed that hypersensitive C-reactive protein?hs-CRP?and gender were the influencing factors of C₀,with statistical significance?P=0.005?.Fifty-eight patients were treated,41 patients were treated successfully,the effective rate was 70.7%.No adverse reactions occurred.According to C₀,32 patients with C₀ less than 10 mg/L and 21 patients with C₀ less than 10 mg/L were treated effectively,the effective rate was 63.6%.There were 24 patients with C₀ in the range of 10-15 mg/L,of whom 18 were treated effectively,the effective rate was 75%.Another 2 patients with C₀ higher than 15 mg/L were treated effectively.3.TDM and analysis of different doses of teicoplanin in the treatment of critically ill hematological patients:A total of 75 patients were enrolled,including 9 in the experimental group and 66 in the control group.The experimental group's monitoring results were less than 10 mg/L in 1 case,10-15 mg/L in 4 cases and 15 mg/L in 4 cases.Seven patients were successfully treated with an effective rate of 77.8%.During the treatment period,no adverse reactions related to teicoplanin occurred.The monitoring results of 66 patients in the control group were less than 10 mg/L in 33 cases,10-15mg/L in 24 cases,and 15 mg/L in 9 cases.45 patients were treated successfully with an effective rate of 68.1%.Conclusions:1.The method established in this study is simple,stable,accurate and reproducible.It can be used for the analysis of plasma samples.Reliable laboratory data for the further monitoring of teicoplanin would be provided by this method.2.There are great individual differences in teicoplanin in patients with severe diseases.The influencing factors of this result are creatinine,hs-CRP and gender.3.The teicoplanin trough concentration is related to the curative effect,and TDM can improve the curative effect.Routine TDM is recommended for patients using teicoplanin.4.Standardized administration of teicoplanin in critically ill patients is not suitable for all patients.Clinical pharmacists and physicians need to adjust the dose according to the renal function of patients,and then adjust the maintenance dose according to the patient's own conditions?such as hs-CRP and gender?and TDM,in order to achieve better therapeutic effect.5.High dose of teicoplanin?load dose:600 mg,q12h,3 doses,maintenance dose:600 mg,qd?can make the blood concentration of critically ill hematological patients reach the target range faster,but this conclusion needs more clinical data to support.