Enterobacteriaceae InfectionsPROBATAZONCT04276480
Efficacy of Piperacillin-tazobactam as Empirical Antimicrobial Therapy for VAP Among ESBL-E Carriers.
A study testing Piperacillin-tazobactam in people with Enterobacteriaceae Infections, run by University Hospital, Bordeaux at 2 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Enterobacteriaceae Infections
- What is being tested?
- Piperacillin-tazobactam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesFrance
- Study dates
- 16 Feb 2022to 22 Apr 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- Pregnancy or breastfeeding
- Curatorship or guardianship
- Prisoners
- No health insurance
Trial locations and contacts
2 sites in 1 country.
France2 sites
Centre hospitalier de la Côte Basque
Bayonne, 64100
Hopital Pellegrin
Bordeaux, 33000
About this study
Official title: 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.
Read the 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.
- Conditions
- Enterobacteriaceae Infections
- Being tested
- Piperacillin-tazobactam
- Keywords
- Fecal carriage, Ventilator-associated pneumonia, Piperacillin-tazobactam
- Medical subject headings
- Enterobacteriaceae Infections, Pneumonia, Ventilator-Associated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Piperacillin-tazobactamDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | The patients included will receive piperacillin-tazobactam as empirical antimicrobial therapy. The empirical microbial therapy will continue until the bacterial susceptibility profile is known. Receives: Drug: Piperacillin-tazobactam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality in Intensive Care Unit (ICU)
Proportion of patients who died during ICU stay.
Measured: at day 28 after inclusion
Secondary outcomes (3)
Proportion of patients cured of infection on D3 and D7 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.
Measured: at day 7 after inclusion
Proportion of patients requiring an escalation of the probabilistic treatment of piperacillin-tazobactam to meropenem.
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.
Measured: at day 28 after inclusion
Mortality at day 90
Proportion of patients who died between D0 and D90
Measured: at day 90 after inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start16 Feb 2022
- Primary completion22 Apr 2024
- Study completion22 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Enterobacteriaceae InfectionsStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laura RICHERT, Dr, Study chair, USMR
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04276480
- Sponsor's protocol ID
- CHUBX 2019/27
- Other IDs
- 2019-A03028-49
- Acronym
- PROBATAZO
- Status last verified
- Aug 2024
- First submitted
- 14 Feb 2020
- Last updated
- 19 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT04276480
- Acronym / sponsor ID
- PROBATAZO / CHUBX 2019/27
- Conditions
- Enterobacteriaceae Infections
- Keywords
- Fecal carriage, Ventilator-associated pneumonia, Piperacillin-tazobactam
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 16 Feb 2022 (actual)
- Primary completion
- 22 Apr 2024 (actual)
- Study completion
- 22 Apr 2024 (actual)
- First posted
- 19 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: Piperacillin-tazobactamThe patients included will receive piperacillin-tazobactam as empirical antimicrobial therapy. The empirical microbial therapy will continue until the bacterial susceptibility profile is known. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Piperacillin-tazobactamAt 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. | Drug | Intervention |
Primary outcome
Mortality in Intensive Care Unit (ICU)
Time frame: at day 28 after inclusion
Proportion of patients who died during ICU stay.
3 secondary outcomes
Proportion of patients cured of infection on D3 and D7 after inclusion
Time frame: 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
Mortality at day 90
Time frame: at day 90 after inclusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laura RICHERT, Dr study chair
USMR
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Piperacillin-tazobactam in people with Enterobacteriaceae Infections, run by University Hospital, Bordeaux at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality in Intensive Care Unit (ICU) (time frame: at day 28 after inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2026.