Clinical Study Of Teicoplanin Pharmacokinetics On Individual Therapy In Patients With Severe G~+ Coccus Infection

Objective:To explore the advantages of teicoplanin pharmacokinetics in patients severely infected by Gram-positive cocci?G⁺?and to seek the influencing factors of drug concentration by analyzing the plasma concentration of teicoplanin,distribution of pathogens,clinical efficacy and drug safety in patients with severe G⁺infection in order toprovide a reference for clinical medication.Methods:This study is a prospective,multi-center and controlled study.Eighty patients with confirmed severe Gram-positive coccus infection from the Chengdu Military General Hospital,the Affiliated Hospital of Chengdu Medial College,People's Hospital of Shuangliu District,and People's Hospital of Xindu District were randomly divided into two groups:the standard group?n=40?and the optimized group(?n=40?.Therapeutic Drug Monitoring?TDM?wasperformedbyHighPerformanceLiquid Chromatography?HPLC?method.The DAS 2.0 software was used to calculate the area under the concentration-time curve?AUC?and the Vitek 2 Compact was used to measured the minimum inhibitory concentration?MIC?,through which we obtained the parameters of pharmacokinetic/pharmacodynamic?PK/PD?of teicoplanin.In the standard group,the dosage regimen of teicoplanin was used according to the drug instructions,whereas the optimized groupwasappliedpersonalizeddosageregimenguidedbythe pharmacokinetics.The compliance rate of target trough concentration?10mg/L?,AUC_0-24/MIC?125 and AUC_0-24/MIC?345 at the 3rd dose and the 6th dose,the efficiency of the drug?the body temperature,the counts of white blood cells?WBC?,the serum concentration of hypersensitive C-reactive protein?HS-CRP?,bacterial clearance,length of hospital stay and survival rate?and the adverse drug reactions?ALT,AST,BUN,SCr,PLT,skin rash?were compared between two groups.Results:TMD was performed by HPLC in these 80patients with severe G⁺infection.The linear regression equation of teicoplanin was Y=14.316X+2.881?r²=0.9999,n=6?.There was a good linear relationship,a high recovery rate and a high accuracy in a range of 3.5¹00ug/ml.When compared with the standard group,the optimized group had significantly higher trough concentration and compliance rate at the 6th dose?11.16±3.16 mg/L vs 8.96±4.10 mg/L,82.5%vs 32.5%,P<0.05?.The AUC_0-24/MIC value and the compliance rate of AUC_0-24/MIC?345 in the optimized group were apparently higher than that in the standard group[?507.97±248.27 vs 328.42±227.62?h,67.5%vs 27.5%,P<0.05].When compared with the standard group,the optimized group had a faster reduction in the count of WBC and the serum concentration of HS-CRP and a higher bacterial clearance rate?80%vs 55%,P<0.05?.The total clinical effective rate in the optimized group was 85%,while the standard groups was 65%?P<0.05?.The optimized group had a little higher trough concentration and the compliance rate of the 3th dose than the standard group had?7.25±3.48 mg/L vs,15%vs 27.5%,P>0.05?.The compliance rates of AUC_0-24/MIC?125 were82.5%and 92.5%in the standard group and the optimized group respectively,but there was no significant difference between two groups?P>0.05?.There were no statistically significance in body temperature changes before&after treatment,the total adverse drug reaction rates and the mortality rates between two groups.The factors signficantly associated with the teicoplanin trough concentration were creatinine clearance rate?CLcr,ml/min?and drug dose?kg,mg/kg?.Closely related to the log 3^rdd dose trough concentration?C3?were the initial loading dose?kg3?and creatinine clearance rate?CLcr3?,while the maintenance dose?kg6?and the day creatinine clearance rate?CLcr6?were closely related to the 6th dose trough concentration?C6?.The best multiple regression equations were as follows:LogC3=0.405+0.068kg3-0.001 CLcr3?VIF 1.023,R²=61.8%,P<0.001?,LogC6=0.92+0.042kg6-0.004CLcr6?VIF1,R²=73.5%,P<0.001?.Conclusion:It is worthy of being clinically popularized for teicoplanin TDM detected by HPLC with its accuracy and reliability.For patients with severe G⁺infection,we recommend that it be better to increase the target trough concentration and AUC_0-24/MIC value of teicoplanin by means of giving a higher dose.The individualized drug regimen of teicoplanin under the guidance of pharmacokinetics is effective and safe in the treatment of patients with severe G⁺infection.Its relationship fitting equation provides a certain reference for clinical medication.