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

NCT04915872 | Completed

• 1 other identifier: CHUBX 2020/53
• Study Type: observational
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Laparotomy; Critical Illness; Piperacillin, Tazobactam Drug Combination

Keywords

Open Abdomen; Negative Pressure Therapy; Antibiotics; Piperacillin - Tazobactam; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (1)

Participant

Critically Ill Patients with Open Abdomen and Negative Pressure Wound Therapy

Procedure: Blood sampling (T0, inclusion); Procedure: other samplings (T1)

Interventions

Blood sampling (T0, inclusion) PROCEDURE

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)

Participant

other samplings (T1) PROCEDURE

\- 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)

Participant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Critically Ill Patients with Open Abdomen and Negative Pressure Wound Therapy

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (1)

CHU de Bordeaux

Bordeaux, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood sample Urinary sample Negative Pressure Therapy fluid sample Peritoneal sampling

MeSH Terms

Conditions

Critical Illness

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: June 7, 2021
• Study Start: July 1, 2021
• Primary Completion: November 18, 2022
• Study Completion: January 27, 2023
• Last Updated: February 27, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)