Observed Pharmacokinetic of Piperacillin/Tazobactam Compared to Amikacin in ICU

Study Overview
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Brief Summary
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The pharmacokinetics of antimicrobials is profoundly modified in Intensive care unit (ICU) patients. To adapt the treatment, it is recommended to measure blood levels of antibiotics. Some antibiotics, such as amikacin, are easy to monitor, while for other molecules, such as piperacillin/tazobactam, the drug monitoring is more difficult to obtain. These two molecules have similar physicochemical characteristics (hydrophilicity) and therefore have closed pharmacokinetic properties. OPTIMA is a study aiming at criteria will be used to judge whether the pharmacokinetic (PK) parameters of amikacin are predictive of those of piperacillin and tazobactam.

Official Title
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Observed Pharmacokinetic of Piperacillin/Tazobactam in ICU Patients Compared to Therapeutic Drug Monitoring of Amikacin

Conditions
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Septic Shock, Sepsis, Sepsis Syndrome

Intervention / Treatment
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* Biological: Plasma dosage of amikacin, piperacillin and tazobactam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient ≥ 18 years old Patient hospitalized in the critical care department of the Lyon-Sud hospital centre Patient with a sepsis or a severe sepsis table defined by the latest international recommendations Patient to be treated by the amikacin + piperacillin/tazobactam association Patient affiliated to a social security system, having agreed to participate in the study Exclusion Criteria: Patient with a known history of hypersensitivity or contraindication to amikacin, piperacillin or tazobactam Patient known to have previously received piperacillin/tazobactam or amikacin combination before inclusion Patient treated at the time of inclusion with dialysis techniques

Ages Eligible for Study
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Minimum Age: 18 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: Patients treated by amikacin and piperacillin<br>ICU patient with a sepsis treated by amikacin and piperacillin/tazobactam | Biological: Plasma dosage of amikacin, piperacillin and tazobactam<br>* Pharmacokinetic (PK) criteria will be used to judge whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma concentration of amikacin during the first 24 hours after administration |  | First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) | 
| Change in plasma concentration of piperacillin during the first 24 hours after administration |  | First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) | 
| Change in plasma concentration of tazobactam during the first 24 hours after administration |  | First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) | 
| Dose administered of amikacin at baseline |  | Hour 0 (Baseline) | 
| Dose administered of piperacillin at baseline |  | Hour 0 (Baseline) | 
| Dose administered of tazobactam at baseline |  | Hour 0 (Baseline) | 
| Change in plasma volume of distribution of amikacin during the first 24 hours after administration | In order to evaluate whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam. Plasma volume of distribution is one of the two PK parameters evaluated in this study (with clearance), calculated with drug plasma concentration and dose administered | First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) | 
| Change in plasma volume of distribution of piperacillin during the first 24 hours after administration | In order to evaluate whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam. Plasma volume of distribution is one of the two PK parameters evaluated in this study (with clearance), calculated with drug plasma concentration and dose administered | First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) | 
| Change in plasma volume of distribution of tazobactam during the first 24 hours after administration | In order to evaluate whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam. Plasma volume of distribution is one of the two PK parameters evaluated in this study (with clearance), calculated with drug plasma concentration and dose administered | First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) | 
| Change in plasma clearance of amikacin during the first 24 hours after administration | In order to evaluate whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam. Plasma clearance is one of the two PK parameters evaluated in this study (with volume of distribution), calculated with drug plasma concentration and dose administered | First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) | 
| Change in plasma clearance of piperacillin during the first 24 hours after administration | In order to evaluate whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam. Plasma clearance is one of the two PK parameters evaluated in this study (with volume of distribution), calculated with drug plasma concentration and dose administered | First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) | 
| Change in plasma clearance of tazobactam during the first 24 hours after administration | In order to evaluate whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam. Plasma clearance is one of the two PK parameters evaluated in this study (with volume of distribution), calculated with drug plasma concentration and dose administered | First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) |