Monitoring of Piperacillin-Tazobactam and Meropenem Plasmatic Levels in Critical Patients

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to establish the Piperacillin-Tazobactam and Meropenem Plasmatic Levels to know if it´s necessary to make some adjustment in the recommended dose regimen.

Official Title
-----------------
Monitoring of Piperacillin-Tazobactam and Meropenem Plasmatic Levels in Critical Patients

Conditions
-----------------
Septic Shock, Sepsis

Intervention / Treatment
-----------------
* Drug: Piperacillin/tazobactam or Meropenem


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients above 18 years old. Hospitalized in the Intense Care Unit. Patients treated with Piperacillin-Tazobactam or Meropenem. Septic shock. Renal hyper clearance. Gram-negative bacillary bacteremia. Continuous renal replacement technique. ECMO. Obesity (BMI> 40). Exclusion Criteria: Patients under 18 years old. Pregnant women.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Piperacillin-Tazobactam or Meropenem Cohort<br>Patients hospitalized for sepsis or septic shock that are treated with Piperacillin-Tazobactam or Meropenem and meet all the inclusion criteria and none of the exclusion criteria. | Drug: Piperacillin/tazobactam or Meropenem<br>* The plasmatic levels determinations will always be made in state of equilibrium (after the fourth dose) and two samples will be collected: Just before the antibiotic infusion (T0) In the midpoint of time (T50). If the antibiotic is administered every 8 hours this determination will be made at 4 hours. If the antibiotic is administered every 6 hours, the determination will be made at 3 hours. A second complete determination will be made (before the infusion, in the midpoint of time and before the next dose) after the administration of 4 doses as long as a posology modification is made as a consequence of the information received from the plasmatic levels.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate if with the currently recommended dose regimen for Piperacillin-Tazobactam and Meropenem are achieved the seric concentrations asociated with the maximum therapeutic efficacy . | The chosen efficiency parameter is that 100 % of the time the concentration remains 4 times above the minimum inhibitory concentration (MIC), the exact minimum inhibitory concentration (MIC) of the used antibiotic will be determined by E-test by the Microbiology Service which means that the seric concentrations asociated with the maximum therapeutic efficacy are: For Meropenem 2mg/dl, which means reaching a concentration in T0 >8 mg/dL. For Piperacillin-Tazobactam 16 mg/dL, which means reaching a concentration in T0 >64 mg/dL. | Up to 12 months after the antibiotic administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate if with the currently recommended dose regimen for Piperacillin-Tazobactam and Meropenem are achieved the seric concentrations asociated with the maximum therapeutic efficacy in patients with renal hyper clearance. | The seric concentrations asociated with the maximum therapeutic efficacy are the same as the described for the description of the Primary Outcome Measure and it´s considered that a patient has renal hyper clearance when they have a creatinine clearance above 130 ml/min. | Up to 12 months after the antibiotic administration | 
| Evaluate if with the currently recommended dose regimen for Piperacillin-Tazobactam and Meropenem are achieved the seric concentrations asociated with the maximum therapeutic efficacy in patients with Gram-negative bacillary bacteremia. | The seric concentrations asociated with the maximum therapeutic efficacy are the same as the described for the description of the Primary Outcome Measure and it´s considered that a patient has Gram-negative bacillary bacteremia when the bloodstream is invaded by Gram-negative bacillary which is diagnosed by blood culture. | Up to 12 months after the antibiotic administration | 
| Evaluate if with the currently recommended dose regimen for Piperacillin-Tazobactam and Meropenem are achieved the seric concentrations asociated with the maximum therapeutic efficacy in patients with continuous renal replacement technique. | The seric concentrations asociated with the maximum therapeutic efficacy are the same as the described for the description of the Primary Outcome Measure and a patient with continuous renal replacement technique, has its blood purified extracorporeally, replacing the renal function continuously 24 hours of the day. | Up to 12 months after the antibiotic administration | 
| Evaluate if with the currently recommended dose regimen for Piperacillin-Tazobactam and Meropenem are achieved the seric concentrations asociated with the maximum therapeutic efficacy in patients with ExtraCorporeal Membrane Oxygenation. | The seric concentrations asociated with the maximum therapeutic efficacy are the same as the described for the description of the Primary Outcome Measure and a patient with ExtraCorporeal Membrane Oxygenation has a short-term extracorporeal circulatory and respiratory mechanical assistance system. | Up to 12 months after the antibiotic administration | 
| Evaluate if with the currently recommended dose regimen for Piperacillin-Tazobactam and Meropenem are achieved the seric concentrations asociated with the maximum therapeutic efficacy in patients with morbid obesity. | The seric concentrations asociated with the maximum therapeutic efficacy are the same as the described for the description of the Primary Outcome Measure and it´s considered that a patient has morbid obesity when it´s BMI (body mass index) is above 40. | Up to 12 months after the antibiotic administration | 
| Determine in the total cohort if with the currently recommended dose regimen for Piperacillin-Tazobactam and Meropenem are achieved the seric concentrations asociated with the maximum therapeutic efficacy. | Determine in the total cohort if with the currently recommended dose regimen for Piperacillin-Tazobactam and Meropenem are achieved the seric concentrations asociated with the maximum therapeutic efficacy. | Up to 12 months after the antibiotic administration | 
| Determine the association between the supra-therapeutic levels and the appearance of toxicity. | Determination of if there´s an association between the antibiotics supra-therapeutic levels and the toxicity appearance. | Up to 12 months after the antibiotic administration | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sepsis, Septic Shock, Piperacillin-Tazobactam, Meropenem, Plasmatic Levels, Critical Patients, Dose adjustment