Piperacillin/Tazobactam in Critically Ill Patients With Severe Sepsis and Septic Shock

Study Overview
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Brief Summary
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This is prospective study to assess the pharmacodynamics (t>MIC) of 4.5 g every 6 h of piperacillin/tazobactam in patients with early phase of severe sepsis/septic shock following administration by a 30 min infusion. Clinical and laboratory data such as age, sex, body weight, electrolyte, vital signs, APACHAE II score, BUN, Cr and fluid balance will be collected. Fifty patients will be enrolled in this study. Piperacillin pharmacokinetic study will be carried out during the piperacillin/tazobactam therapy. Each patient received 4.5 g every 6 h of piperacillin/tazobactam within 24 h of severe sepsis or septic shock, blood samples (approximately 3 ml) will be obtained by direct venipuncture at the following time: 0, 0-0.5, 0.5-2, 2-4 and 4-6 h after piperacillin/tazobactam therapy. Concentration of piperacillin in plasma will be simulated in Monte Carlo technique to get PK/PD index and reported to % PTA and % CFR.

Official Title
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Population Pharmacokinetics and Pharmacodynamics Study of Piperacillin/Tazobactam During Early Phase in Critically Ill Patients With Severe Sepsis

Conditions
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Early Phase of Severe Sepsis and Septic Shock

Intervention / Treatment
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* Drug: Piperacillin-tazobactam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: sepsis patient (defined by 2011 SCCM/ESICM/ACCP/ATS/SIS International sepsis definition conference) severe sepsis or septic sock was defined by Severe sepsis (sepsis with organ dysfunction) Septic shock (sepsis with systolic arterial pressure<90 mmHg, mean arterial pressure<60 mmHg or decrease systolic blood pressure> 40 mmHg from base line) Exclusion Criteria: Patients who are pregnant. Patients who have documented hypersensitivity to beta-lactam Patients who are dialysis Patients who are severe sepsis or septic shock more than 24 hour

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: piperacillin/tazobactam<br>4.5 g of piperacillin/tazobactam in 100 ml of normal saline solution was administered via an infusion pump at a constant flow rate 30 min every 6 h | Drug: Piperacillin-tazobactam<br>* 4.5 g of piperacillin/tazobactam in 100 ml of normal saline solution was administered via an infusion pump at a constant flow rate 30 min every 6 h and blood sample were obtained by direct venepuncture at 0, 0-0.5, 0.5-2, 2-4 and 4-6 hour after drug administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of piperacillin in plasma | Concentration of piperacillin in plasma will be simulated in Monte Carlo simulation to assess PK/PD index as 40% and 100% T>MIC and will be reported as %PTA. | 6 hour after the piperacillin dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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piperacillin/tazobactam, critically ill, severe sepsis, septic shock