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

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.

Study Overview

• Status: Unknown
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Drug: Piperacillin/tazobactam or Meropenem

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• Spain
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen Macarena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with sepsis or septic shock who are being treated with Meropenem or Piperacillin-Tazobactam and meet the following criteria and none of the exclusion criteria.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Piperacillin-Tazobactam or Meropenem Cohort; 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; 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.

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

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Investigators: Principal Investigator: José Garnacho Montero, Hospital Universitario Virgen Macarena

Study record dates

Study Major Dates

• Study Start (Anticipated): February 15, 2020
• Primary Completion (Anticipated): December 15, 2020
• Study Completion (Anticipated): March 15, 2021

Study Registration Dates

• First Submitted: February 4, 2020
• First Submitted That Met QC Criteria: February 4, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): February 6, 2020
• Last Update Submitted That Met QC Criteria: February 4, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Septic Shock; Sepsis; Meropenem; Plasmatic Levels; Dose adjustment; Piperacillin-Tazobactam; Critical Patients
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Shock, Septic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Meropenem; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination
• Other Study ID Numbers: FIS-MER-2019-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No