PK/PD of Extended-infusion Meropenem, Piperacillin-tazobactam and Cefepime in the Early Phase of Septic Shock

Study Overview
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Brief Summary
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This study evaluates PK/PD of an extended-infusion protocol of meropenem, piperacillin-tazobactam and cefepime, in the early phase of septic shock.

Detailed Description
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Beta Lactams are the keystones of shock septic treatment. Early phase of septic shock is a period of disturbed pharmacokinetics, with augmented renal clearance and distribution volume of hydrophilic drugs as Beta Lactams. Consequently, early phase of septic shock is a period at risk of underdosing Beta Lactam, which could increase the risk of clinical failure an mortality. Data are available concerning underdosing of MEROPENEM, PIPERACILLIN-TAZOBACTAM and CEFEPIME, when administered in bolus. No data exist concerning the achievement of a target of 100% of the whole interval above 4 time the superior breakpoint of Pseudomonas Aeruginosa according to EUCAST (European Committee on Antimicrobial Susceptibility Testing), during the 48 first hours of treatment of septic shock, when Beta Lactam are administered in extended infusion.

Official Title
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Pharmacokinetics and Pharmacodynamic (PK/PD) of Extended-infusion Meropenem, Piperacillin-tazobactam and Cefepime in the Early Phase of Septic Shock

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: MEROPENEM
* Drug: PIPERACILLIN-TAZOBACTAM
* Drug: CEFEPIME


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Septic shock Meropenem, piperacillin-tazobactam or cefepime started after enrollment Exclusion Criteria: Pregnancy Central nervous system infection Burns

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MEROPENEM<br>After enrollment, patients of MEROPENEM arm will receive an initial 2g bolus of MEROPENEM and 2g infusion over 3 hours every eight hours, during 48 hours, without modification of rhythm and dose according to renal function. | Drug: MEROPENEM<br>* Administration of MEROPENEM according to a protocol of extended infusion defining dose and duration of infusion.<br>|
| Active Comparator: PIPERACILLIN-TAZOBACTAM<br>After enrollment, patients of PIPERACILLIN - TAZOBACTAM arm will receive an initial 4g bolus of PIPERACILLIN - TAZOBACTAM and a 16g continuous infusion per day, during 48 hours, without modification of rhythm and dose according to renal function. | Drug: PIPERACILLIN-TAZOBACTAM<br>* Administration of PIPERACILLIN-TAZOBACTAM according to a protocol of continuous infusion defining dose and duration of infusion.<br>|
| Active Comparator: CEFEPIME<br>After enrollment, patients of CEFEPIME arm will receive an initial 2g bolus of CEFEPIME and a 6g continuous infusion per day, during 48 hours, without modification of rhythm and dose according to renal function. | Drug: CEFEPIME<br>* Administration of CEFEPIME according to a protocol of continuous infusion defining dose and duration of infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving the PK/PD target | Proportion of patients achieving the target of 100% of 48 first hours of treatment above 4 time the upper critical breakpoint for Pseudomonas Aeruginosa | First 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality |  | 28th day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Septic shock, Beta Lactams, Extended infusion, PK/PD