Assessment of the Optimal Dosing of Piperacillin-tazobactam in Intensive Care Unit Patients: Extended Versus Continuous Infusion

Study Overview
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Brief Summary
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Piperacillin-tazobactam is an acylureido-penicillin-beta-lactamase inhibitor combination and is frequently used in the empirical treatment of hospital-acquired infections because of its antipseudomonal activity. Similar to other beta-lactam antibiotics, piperacillin-tazobactam exhibits time-dependent killing and the T > MIC appears to be the best outcome predictor. Because a majority of infections are treated empirically, it is necessary to achieve a T > MIC equal to 50% of the dosing interval (50% T > MIC) against the most likely pathogens, including those with only moderate susceptibility The aim of this study is to compare the same dose of piperacillin/tazobactam administered by an extended infusion versus a continuous infusion. A pharmacokinetic study will be performed in patients treated by extended (loading dose 4 G/30 min followed by 4 X 4 G /3h) and continuous infusion (loading dose 4 G/30 min followed by 16G /24h). A population pharmacokinetic analysis with Monte Carlo simulations will be used to determine 95% probability of target attainment (PTA95) versus MIC

Official Title
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Assessment of the Optimal Dosing of Piperacillin-tazobactam in Intensive Care Unit Patients: Extended Versus Continuous Infusion

Conditions
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Infectious Disease

Intervention / Treatment
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* Drug: piperacillin continuous infusion
* Drug: piperacillin extended infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (> 18 years) admitted on the intensive care unit (surgical and medical surgery). Starting a treatment with piperacillin/tazobactam Signed informed consent Hematocrit >= 21% Available arterial line Exclusion Criteria: age <18 or >75 years patient's weight <50 or >100 kg renal insufficiency (estimated clearance < 50 ML /MIN) haemodialysis WBC < 1000 103 µl estimated survival <5 days meningitis or other proven infections of the CNS IgE-mediated allergy to penicillins pregnancy patients having participated in another study <30 days before inclusion in the present study retrospectively, marked deterioration of the renal function during the study period retrospectively, treatment < 96 h

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: extended infusion<br> | Drug: piperacillin extended infusion<br>* piperacillin extended infusion<br>|
| Experimental: continuous infusion<br> | Drug: piperacillin continuous infusion<br>* piperacillin continuous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetics of piperacillin continuous infusion compared to piperacillin extended infusion | Determination of serum concentrations of piperacillin. | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 95% probability of target attainment (PTA95) versus MIC of different organisms. | Determination of the probability of target attainment versus MIC of different organisms. | 96 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infectious disease, piperacillin, continuous infusion, extended infusion