Therapeutic Drug Monitoring of Anti-infectious Drugs in Intensive Care Unit (STP-ATB-REA)

Evaluation of the Use of Therapeutic Drug Monitoring in the Management of Infections in Intensive Care Unit Patients.

This research targets four anti-infectives commonly prescribed in intensive care: ceftazidime, cefepime, cefotaxime and meropenem, used for severe infections For patient hospitalized in intensive care unit , there is little or no pharmacokinetic data for these four molecules.

Study Overview

• Status: Unknown
• Conditions: Infection, Bacterial
• Intervention / Treatment: Other: Blood sample

Detailed Description

Antibiotics, and especially beta-lactams, are among the most used drugs in the world. The good use of antibiotics and the prevention of selection of resistant strains has been a public health priority for many years. In this context, it is essential to obtain effective antibiotic concentrations at the site of infection. In order to obtain effective concentrations, ceftazidime, cefepime, cefotaxime, piperacillin and meropenem are administered in this population by continuous infusion at high dose. Although beta-lactams are mostly well tolerated, they can cause adverse effects such as severe neurological toxicities.

The critically ill patient has physiological alterations that can significantly alter the pharmacokinetics of drugs. Several studies have clearly shown that the pharmacokinetics of beta-lactams in the critically ill patient is different from those of other patients. Depending on the clinical context and the co-morbidities of the patient, sub-therapeutic or potentially toxic concentrations can be observed for the same dosage. The risk of ineffective treatment and the development of resistance remains, despite the high doses administered. In addition, this pharmacokinetic variability may be responsible for the observation of toxic concentrations and the occurrence of adverse effects in this population.

Following these arguments, therapeutic drug monitoring (TDM) of beta-lactams accompanied by personalized dosage adjustment appears to be an essential tool to optimize the management of critically ill patients. Although strongly recommended, the TDM of beta-lactams in the critically ill patient accompanied by a dosage adjustment is not currently performed systematically in all patients.

The objective of this study is to evaluate the impact of the use of a systematic therapeutic drug monitoring of beta-lactams in the critically ill treated with cefotaxime, ceftazidime, cefepime, meropenem or piperacillin, in terms of efficacy and prevention of neurotoxicity.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Romain GUILHAUMOU; Phone Number: +33 491.38.96.56/75.65; Email: Romain.GUILHAUMOU@ap-hm.fr
• Study Contact Backup: Name: Lionel VELLY; Phone Number: +33 4 13 42 94 61; Email: lionel.velly@ap-hm.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patient (age> 18 years)
• Patient hospitalized in intensive care for a duration greater than 7 days, treated with cefotaxime, ceftazidime, cefepime, piperacillin or meropenem according to a standardized dosing regimen.

Exclusion Criteria:

• Age <18
• Pregnant woman
• Patient allergic to beta-lactams
• No written informed consent by the patient or his/her (legal) representative

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: blood sample group; Adult patient hospitalized in intensive care unit and treated for infection.	Other: Blood sample; The blood samples will be taken from the patient's bed and then sent to the clinical pharmacology laboratory of Prof. Blin (DRC, Bat F, Timone Hospital).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
dosage of betalactamins concentrations	Target concentrations are determined from the PK/PD target defined for betalactamins in the intensive care patient, ie a steady-state concentration 100% of the time at 4-5xMIC.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy of the treatment with the clinical response at the end of treatment	Evaluate the efficacy of the treatment with the clinical response at the end of treatment and/or J14 according to the criteria of "resolution / improvement / failure" according to De Waele et al. (Intensive Care Medicine 2014 Sep; 40 (9): 1340-51)	14 days

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Anticipated): January 2, 2018
• Primary Completion (Anticipated): June 2, 2020
• Study Completion (Anticipated): October 31, 2020

Study Registration Dates

• First Submitted: November 8, 2017
• First Submitted That Met QC Criteria: November 8, 2017
• First Posted (Actual): November 13, 2017

Study Record Updates

• Last Update Posted (Actual): November 14, 2017
• Last Update Submitted That Met QC Criteria: November 10, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bacterial Infections and Mycoses; Infections; Bacterial Infections
• Other Study ID Numbers: 2017-05

Drug and device information, study documents

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