Pharmacokinetic Of Piperacillin/Tazobactam In Patients With Sepsis During Continuous Venovenous Hemodiafiltration

Objective:To evaluate the pharmacokinetic of Piperacillin/Tazobactam in Patients with sepsis during Continuous Venovenous Hemodiafiltration(CVVHDF)and to analyse the influencing factors.Method:A prospective,observational pharmacokinetics study in the intensive care units in a general hospital during June 2014 to May 2016,the patients with sepsis requiring Continuous renal replacement therapy(CRRT)were enrolled as the subjects.The study protocol was approved by the hospital ethics committee and all patients(or their surrogate decision-makers)provided written informed consent to participate in the study.First dose of Piperacillin-tazobactam(4.5g)(Tazocine,Wyeth Pharmaceutical Co.Ltd,USA)was administered intravenously over 30 min.Blood samples were taken at 0,15,30,45,60,90,120,180,240,360,480min after infusion.The concentrations of piperacillin and tazobactam were determined by high-performance liquid chromatography(HPLC),use Agilent1260 HPLC analyzer,chromatographic column:Agilent ZORBAX SB-C18(4.6 mm×150 mm,5μm).Describe the concentration-time curve,PK analysis was conducted using a non-compartmental approach,the DAS 3.2.1 software was used to calculate pharmacokinetic parameters,Linear regression analysis was used to analyze the relationship between patient characteristics/CRRT parameters and pharmacokinetics.Blood concentration maintained above the minimum inhibitory concentration(MIC)for 50%(f%T>MIC>50%)as a pharmacodynamic target.Result:Eight patients with sepsis receiving CVVHDF were included in the investigation,the median age was 54(47-62)years,the median APACHE II score was 23.5(19.3-29.8),the median SOFA score was 9(7.3-12.3);the replacement flow rate was 2.0(2.0-2.4)L/h,the dialysate rate was 1.0(1.0-1.9)L/h,the effluent flow rate was 59.3(52.3-73.1)ml/kg/h.The maximum concentration(Cmax)of Piperacillin and Tazobactam was 116.11(98.03-152.29)and 21.60(15.9-29.69)mg/L respectively;The volume of distribution(Vd)was 1.05(0.7-1.56)and 0.69(0.56-0.78)mg/L/h respectively;The elimination half-time(t1/2)was 4.79(3.30-8.27)and 4.38(3.35-5.52)h respectively;The total clearance rate(CL)was 7.67(5.66-9.71)and 6.11(4.36-10.03)L/h respectively.In the multivariate analysis,the most significant factor associated with Cmax of Piperacillin was replacement flow rate(β:-0.854,95%CI:-0.148～-0.854,p=0.007),the most significant factor associated with CL of Piperacillin was effluent flow rate(β:0.883,95%CI:0.133～0.433,p=0.004).When MIC≤16mg/L,all patients reached pharmacodynamic target,when 16<MIC<32mg/L,just 5 patients(62.5%)reached the target,while MIC≥64ml/L,no patient reach the target.Conclusion:Whether piperacillin or tazobactam in patients with sepsis receiving CVVHDF,showed significantly lower Cmax,significantly longer t1/2,and CL decreased.CL and t1/2 remained consistent.when germ’s MIC>32mg/L,the dosage regimen of piperacillin/tazobactam(4g/0.5g)Q8H had a greater risk of failure,it may be necessary to change the antibiotics or combine the drugs.