Efficacy of Piperacillin-tazobactam as Empirical Antimicrobial Therapy for VAP Among ESBL-E Carriers. (PROBATAZO)

May 18, 2026 updated by: University Hospital, Bordeaux

Antimicrobial Therapy for Ventilator-associated Pneumonia Among Patients Colonized With Extended-spectrum Beta-lactamase-producing Enterobacteriaceae : Efficacy of a Strategy Using Piperacillin-tazobactam as Empirical Treatment.

Antimicrobial resistance is a major threat worldwide and now concerns last-ressource antibiotics such as carbapenems. As the resistance to carbapenems is directly due to their use, their spare has become a public health emergency. Their efficacy in ventilator-associated pneumonia has never been compared to other classes of antibiotics such as piperacillin-tazobactam which can be an alternative to carbapenems.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The rising antimicrobial resistance has led to more than 33,000 deaths in Europe in 2015. Among them, extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are the most frequent in Europe and carbapenems are recommended as a first line treatment by the guidelines despite the fact they are last-resource agents. Nevertheless, the overuse of carbapenems triggered the emergence of carbapenems-resistant Enterobacteriaceae (CRE). Alternatives to carbapenems are needed to treat ESBL-E infections efficiently without selecting CRE. One strategy described during the last few years is to guide the empirical antimicrobial therapy upon the fecal carriage of ESBL-E. In fact, ESBL-E fecal carriers are more often colonised in the lungs with ESBL-E and have more subsequent ESBL-E infections than non-carriers. However, the positive predictive value of ESBL-E fecal carriage for subsequent ESBL-E is only of 40% despite a negative predictive value of almost 100%. Besides, a before-after cohort study with and without ESBL-E fecal carriage screening exhibited a decrease of carbapenems consumption without any clinical harm. Several studies compared carbapenems vs alternatives after ESBL-E documentation and did not find any clinical harm either but carbapenems were almost always used before documentation. At the best of our knowledge, no study prospectively investigated an alternative to carbapenems for the empirical antimicrobial therapy (before documentation) of ventilator-associated pneumonia despite those encouraging data. This study aims to assess the relevance of piperacillin-tazobactam as the empirical antimicrobial therapy in case of a ventilator-associated pneumonia among ESBL-E fecal carriers. The treatment will be then adapted according to the susceptibility profile. The follow-up of the patients will last until 28 days after their inclusion and until their discharge from intensive care unit if it occurs later. Bacterial susceptibility to the antimicrobial treatment and clinical outcomes will be recorded.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Bayonne, France, 64100
        • Centre Hospitalier de la côte Basque
      • Bordeaux, France, 33000
        • Hôpital Pellegrin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient above 18 year-old admitted to intensive care unit
  • ESBL-E fecal carriage according to current screening recommendations
  • Suspicion of ventilator-associated pneumonia according to ICU society guidelines

Exclusion Criteria:

  • Septic shock according to Sepsis-3 classification
  • Neutropenia (neutrophils count < 500/mm3)
  • Known fecal carriage of Carbapenemase-producing Enterobacteriaceae or multi-drug resistant A. baumanii during the past 6 months.
  • Infection with a bacteria resistant to piperacillin-tazobactam during the past 6 months
  • Treatment with piperacillin-tazobactam in the 10 previous days
  • Proven hypersensitivity to penicillin or tazobactam
  • Pregnancy or breastfeeding
  • Curatorship or guardianship
  • Prisoners
  • No health insurance

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Intervention
The patients included will receive piperacillin-tazobactam as empirical antimicrobial therapy. The empirical microbial therapy will continue until the bacterial susceptibility profile is known.
Drug: Piperacillin-tazobactam

At the time of ventilator-associated pneumonia diagnosis, patients will receive an initial 4g loading dose of piperacillin-tazobactam with a continuous maintenance dose of 16g per day the first day of treatment. The dose of the piperacillin-tazobactam administered the following days will be adjusted to the renal function.

The antimicrobial treatment will be adjusted to the narrower-spectrum agent after the antimicrobial susceptibility determination for a total length of treatment of seven days.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mortality in Intensive Care Unit (ICU)
Time Frame: at day 28 after inclusion
Proportion of patients who died during ICU stay.
at day 28 after inclusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of patients cured of infection on D3 and D7 after inclusion
Time Frame: at day 7 after inclusion
The proportion of cured patient is defined by the combination of : hemodynamic stability, a stable or improving SOFA score AND a stable or improving Pa02 / FiO2 ratio.
at day 7 after inclusion
Proportion of patients requiring an escalation of the probabilistic treatment of piperacillin-tazobactam to meropenem.
Time Frame: at day 28 after inclusion
Therapeutic escalation of piperacillin-tazobactam to meropenem will be performed in patients in whom septic shock according to the Sepsis-3 criteria appears between inclusion and obtaining microbiological documentation and in patients in whom the condition respiratory threatens the short-term life-threatening.
at day 28 after inclusion
Mortality at day 90
Time Frame: at day 90 after inclusion
Proportion of patients who died between D0 and D90
at day 90 after inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Bordeaux

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Laura RICHERT, Dr, USMR

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 16, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 22, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 22, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 14, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 17, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 19, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 19, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CHUBX 2019/27
  • 2019-A03028-49 (Other Identifier: ANSM)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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