Are Standard Dosing Regimens of Piperacillin-Tazobactam Suitable in Critically Ill Patients With Open Abdomen and Negative Pressure Wound Therapy? A Population Pharmacokinetic Study. (PK-LAP)

For several years, open abdomen with temporary abdominal closure using Negative Pressure Therapy (OA/NPT) has become one of the leading strategies to treat or prevent intra-abdominal hypertension in critically ill surgical patients after a wide range of complex abdominal injuries and conditions.

According to current practice, piperacillin-tazobactam (PTZ) is widely used as part of empirical combined antibiotic therapy to treat severe abdominal infections in the critically ill patients. On the other hand, little is known about the impact of OA/NPT on antibiotics pharmacokinetics and pharmacodynamics (PK/PD) and the optimal dosing regimens in this population remain unclear.

As PTZ is a small hydrophilic molecule with a very low level of protein binding, invesitigators hypothesized that OA/NPT should lead to significant changes in volume of distribution (Vd) and/or drug clearance (CL

The main objective of this study was to assess the incidence of underdosing and the pharmacokinetics of piperacillin in critically ill patients with OA/NPT.

The secondary objective was to assess the appropriateness of recommended regimens for empirical minimum inhibitory concentration (MIC) coverage.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Laparotomy; Piperacillin, Tazobactam Drug Combination
• Intervention / Treatment: Procedure: Blood sampling (T0, inclusion); Procedure: other samplings (T1)

• Study Type: Observational
• Enrollment (Actual): 46

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • CHU de Bordeaux

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: Probability Sample

Study Population

Critically Ill Patients with Open Abdomen and Negative Pressure Wound Therapy

Description

Inclusion Criteria:

• Age ≥ 18
• Admitted in surgical ICU for a suspected length of stay > 3 days
• Receiving an antimicrobial therapy by PTZ
• For an intra-abdominal infection
• Under OA/NPT during antimicrobial therapy
• With urinary and arterial catheters

Exclusion Criteria:

• Severe renal failure (CLCR < 30 ml/min) without indication for continuous renal replacement therapy (CRRT)
• Known allergy to PTZ
• Patient's refusal for participation to the research
• Patient unable to consent (dementia or severe psychiatric disorders, people under legal protection, people deprived of their liberty...)
• Pregnancy or breast-feeding

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Participant; Critically Ill Patients with Open Abdomen and Negative Pressure Wound Therapy

Procedure: Blood sampling (T0, inclusion); Blood sample (5 ml) at 30 minutes after the loading dose of 4g/0.5g over 30 minutes for therapeutic drug monitoring at peak concentration (Cmax); Procedure: other samplings (T1); - T1 : Day of the first surgical revision, under PTZ administered by continuous infusion : Blood sample (5 ml) for therapeutic drug monitoring at steady state concentration (Css). Urinary sample and collection of urinary volume between T0 and T1 (Urinary Clearance) NPT fluid sample and collection of NPT volume between T0 and T1 (Peritoneal Clearance) Peritoneal sampling for therapeutic drug monitoring at the site of infection (CPt)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of piperacillin	The main outcome investigated in this study was the rate of piperacillin (PIP) underdosing, arbitrarily defined by at least one of three samples under 16 mg/L. This threshold represents the highest MIC for Pseudomonas as per the European Committee on Antimicrobial Susceptibility Testing (EUCAST).	T1 (Day of the first surgical revision, up to 72 hours after inclusion)

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Actual): November 18, 2022
• Study Completion (Actual): January 27, 2023

Study Registration Dates

• First Submitted: February 1, 2021
• First Submitted That Met QC Criteria: June 4, 2021
• First Posted (Actual): June 7, 2021

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 24, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Antibiotics; Negative Pressure Therapy; Open Abdomen; Piperacillin - Tazobactam
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: CHUBX 2020/53

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