Target Attainment of TDM-guided Infusion of Piperacillin/Tazobactam and Cefepim in Critically Ill Patients (DOSATB)

Target Attainment of TDM-guided Continuous Infusion of Piperacillin/Tazobactam and Cefepim in Critically Ill Patients: a Prospective Observational Study

Although alternative dosing strategies can improve antimicrobial exposure in critically ill patients, the high PK variability in this population means that some may still receive sub-optimal antibiotic exposure leading to unfavourable clinical outcomes.

Therapeutic drug management (TDM) guided dosing is the only safe and effective way to ensure that all critically ill patients achieve therapeutic antimicrobial exposures and to minimise the likelihood of toxicity.

For experts, TDM should be a standard of care, in particular for β-lactams. Nevertheless, because of the assay method for β-lactams and the need for bioanalytical experts, delays in obtaining results frequently occurred. These barriers, combined with difficulties in the interpretation of TDM results, need to be addressed in order to increase its routine utilization. Consequently, study aiming at identify which subgroup of patients or infection are more likely to benefit from TDM are urgently warranted This prospective observational study aimed at evaluating target attainment of piperacillin/tazobactam (PIP/TAZ) and cefepim (CEF) with the use of a Therapeutic Drug Monitoring (TDM) in critically patients during the routine care

Study Overview

• Status: Completed
• Conditions: Sepsis; Critical Illness; Septic Shock; Antibiotic Toxicity
• Intervention / Treatment: Other: dosage of concentration of piperacillin and cefepim

• Study Type: Observational
• Enrollment (Actual): 99

Contacts and Locations

Study Locations

• France
  • Vandoeuvre les Nancy, France, 54500
    • Central Hospital
  • Lorraine
    • Vandoeuvre Les Nancy, Lorraine, France, 54500
      • Emmanuel NOVY

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

Critically ill patients admitted to the surgical intensive care unit whatever the reason of admission and who received piperacilin or cefepim with a TDM for sepsis or septic shock during their stay.

Description

Inclusion Criteria:

• Minimun age limits 18 years
• Critically ill patient receiving piperacillin or cefepim administered continuously

Exclusion Criteria:

• Beta lactam allergy
• Pregnancy
• Age less than 18 years

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
critically ill patients; Critically ill patients receiving continuous infusion of piperacillin/tazbactam or cefepim and dosage of plasma concentration of the B lactam administered	Other: dosage of concentration of piperacillin and cefepim; Dosage of total plasma concentration of piperacillin and cefepim at different timepoints

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
to determine the percentage of patients who met the PK/PD targets at 24 hours	PK/PD target was defined as follows: Concentration of piperacillin or cefepim between a lower and a upper limit: The lower limit was defined as estimated free concentration above 4 times the epidemiological cut-off value of suspected bacteria; The upper limit was based on known limit of neurotoxicity, namely 35 and 160 mg/L for cefepim and piperacillin, respectively Consequently : for piperacillin : the PK/PD target is considered to be reach if the free concentration of PIPERACILLIN/TAZOBACTAM is between 32 and 160 mg/l; for cefepim : the PK/PD target is considered to be reach if the free concentration of CEFEPIM is between 4 and 35 mg/l	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
to determine the percentage of patients who met the PK/PD targets "exposure" at 24 hours	PK/PD target "exposure" take into account only the the lower limit was defined as estimated free concentration above 4 times the epidemiological cut-off value of suspected bacteria Consequently : for piperacillin : the PK/PD target is considered to be reach if the free concentration of PIPERACILLIN/TAZOBACTAM is above 32 mg/l; for cefepim : the PK/PD target is considered to be reach if the free concentration of CEFEPIM is above 4 mg/l	Day 1
factors associated with target attainment at day 1	effect of age on antibiotic concentration	Statistical analysis after 2 years of inclusion
factors associated with target attainment at day 1	effect of renal clearance on antibiotic concentration	Statistical analysis after 2 years of inclusion
factors associated with target attainment at day 1	effect of presence of septic shock on antibiotic concentration	Statistical analysis after 2 years of inclusion
factors associated with dose changing	effect of presence of septic shock on number of dose changing after analyse of antibiotic concentration	Statistical analysis after 2 years of inclusion
factors associated with dose changing	effect of renal clearance on number of dose changing after analyse of antibiotic concentration	Statistical analysis after 2 years of inclusion

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: Emmanuel NOVY, Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 2, 2018
• Primary Completion (ACTUAL): November 1, 2019
• Study Completion (ACTUAL): November 2, 2019

Study Registration Dates

• First Submitted: August 24, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (ACTUAL): August 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 28, 2020
• Last Update Submitted That Met QC Criteria: August 26, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: therapeutic drug monitoring
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Anti-Infective Agents; Anti-Bacterial Agents; Piperacillin
• Other Study ID Numbers: PSS2018/DOSATB-NOVY/YB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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