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

NCT ID: NCT04915872

Last Updated: 2023-02-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

46 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-07-01

Study Completion Date

2023-01-27

Brief Summary

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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.

Detailed Description

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Conditions

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Laparotomy Critical Illness Piperacillin, Tazobactam Drug Combination

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Participant

Critically Ill Patients with Open Abdomen and Negative Pressure Wound Therapy

Blood sampling (T0, inclusion)

Intervention Type 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)

Intervention Type 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)

Interventions

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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)

Intervention Type 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)

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Bordeaux

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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CHU de Bordeaux

Bordeaux, , France

Site Status

Countries

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France

Other Identifiers

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CHUBX 2020/53

Identifier Type: -

Identifier Source: org_study_id

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