PK/PD and Clinial Outcomes of Beta-lactams in ICU Patients

Study Overview
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Brief Summary
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Meropenem and imipenem are broad-spectrum carbapenem antibiotic and are frequently prescribed in critically ill patients with severe infections. These patients show several pathophysiological changes that may alter the carbapenem pharmacokinetic (PK) normally found in other populations. Although the PK of carbapenems has been widely studied, most studies have been conducted on small populations, and clinical outcome data are sparse. Therefore, the aims of this study are (i) describe the population pharmacokinetic parameters of meropenem and imipenem in critically ill subject (ii) evaluate the pharmacodynamic of meropenem and imipenem as a predictor of clinical treatment outcome.

Official Title
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Pharmacokinetics/Pharmacodynamics and Clinical Outcomes of β-lactams in Critically Ill Patients

Conditions
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Critical Illness, Bacterial Infections

Intervention / Treatment
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* Drug: Meropenem
* Drug: Imipenem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >18 years severely ill patient who admitted to medical or surgical intensive care unit who require a treatment with meropenem or imipenem antibiotic Exclusion Criteria: severe renal impairment and require renal replacement therapy APACHE II score >30 History of hypersensitivity to carbapenems Pregnancy or breast-feeding female

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Meropenem<br>Critically ill patients who require meropenem therapy | Drug: Meropenem<br>* This group is composed of 52 critically ill patients, meropenem dosage is chosen by the intensivist in charge of the case. Blood sampling: 5 blood samples (3 mL) were obtained from a heparinized intravascular catheter by direct venipuncture at the following time: before (time 0) and during 0-0.5 h, 0.5-2.5 h, 2.5-4 h, 4-8 h or 4-12 after meropenem administration.<br>|
| Imipenem<br>Critically ill patients who require imipenem therapy | Drug: Imipenem<br>* This group is composed of 50 critically ill patients, imipenem dosage is chosen by the intensivist in charge of the case. Blood sampling: 5 blood samples (3 mL) were obtained from a heparinized intravascular catheter by direct venipuncture at the following time: before (time 0) and during 0-0.5 h, 0.5-2 h, 2-4 h, 4-6 h or 4-12 after imipenem administration.<br>* Other names: Imipenem/cilastatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Population pharmacokinetic parameters of meropenem and imipenem |  | 24-48 hours after treatment | 
| %fT>MIC of meropenem and imipenem | the percentage of time which the free drug concentration remains above the minimum inbibitory concentration (%fT>MIC) | 24-48 hours after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The relationship between %fT>MIC and clinical cure | Clinical cure: disappearance of all signs and symptoms related to the infection, such that no additional antibacterial therapy, drainage, or surgical procedure was required. | Day 3-7 after treatment and end of therapy (7-14) | 
| The relationship between %fT>MIC and microbiological cure | Success is eradication (absence of the baseline pathogen in a specimen appropriately obtained from the original site of infection) or presumed eradication (absence of material to culture in a subject who was assessed as a clinical cure). | Day 3-7 after treatment and end of therapy (7-14) | 
| The relationship between %fT>MIC and mortality | All-cause mortality | during hospital stay and at day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, pharmacodynamics, meropenem, imipenem