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

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.

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Key information

Conditions

Laparotomy Critical Illness Disease Attributes Pathologic Processes Pathological Conditions, Signs and Symptoms Piperacillin, Tazobactam Drug Combination

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

CHU de Bordeaux

Bordeaux, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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)

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)

Primary outcomes

Rate of piperacillin

Time frame: T1 (Day of the first surgical revision, up to 72 hours after inclusion)

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).

Sponsors and collaborators

Lead sponsor

University Hospital, Bordeaux

Other

Registry information

Acronym: PK-LAP

Important dates

Study start: 2021
Primary completion: 2022
Study completion: 2023
First posted: Jun 7, 2021
Registry last updated: Feb 27, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed