Individualized beta‑lactam dosing with piperacillin (drug combination) for ICU patients with sepsis caused by gram‑negative bacteria

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What is this study about?

Patients with sepsis in the intensive care unit often receive antibiotics from the beta-lactam class, such as piperacillin, tazobactam, amoxicillin, cefotaxime, cefepime, ceftazidime, avibactam and meropenem. Sepsis is a serious condition where the body’s response to infection can damage its own organs, and prompt, effective antibiotic treatment is crucial.

The study aims to determine whether an individualized approach that combines therapeutic drug monitoring, minimal inhibitory concentration and model-based dose adjustment can improve outcomes for these patients. Therapeutic drug monitoring means measuring the amount of antibiotic in the blood, minimal inhibitory concentration is the lowest drug level that stops bacterial growth, and model-based dose adjustment uses computer calculations to set the right dose.

Participants will be randomly assigned to receive the standard antibiotic regimen or the individualized regimen. In the individualized group, blood samples are taken shortly after the infusion to check drug levels, and doses may be modified based on the results. Patients are followed for up to 28 days to record time spent in the intensive care unit, need for breathing support or kidney treatment, and survival, without any additional procedures beyond routine care.

1 enrollment and baseline assessment

after joining the study you give informed consent and provide basic health information.

a blood sample is taken to measure the level of the antibiotic that will be used (therapeutic drug monitoring) and to determine the minimal inhibitory concentration (the lowest amount of drug that stops the bacteria).

2 start of antibiotic infusion

you receive an intravenous infusion of a beta‑lactam antibiotic selected for the study.

possible drugs and their usual doses are:

piperacillin 12 g, tazobactam 1.5 g per litre, amoxicillin 12 g, cefotaxime 12 g, cefepime 6 g, ceftazidime 6 g, meropenem 6 g, and avibactam 1.5 g.

the infusion is given once a day (or as a continuous infusion according to the hospital protocol) for up to 7 days, or until you leave the intensive care unit, whichever comes first.

3 daily blood sampling for drug level monitoring

each day while you are receiving the antibiotic, a small amount of blood is drawn to check the drug concentration in your bloodstream.

these results are used to keep the drug level within the range that is effective against the infection.

4 dose adjustment based on monitoring

if the daily blood test shows that the drug level is too low or too high, the medical team may change the amount of drug you receive.

dose changes can occur during the first 7 days of treatment to ensure optimal effectiveness and safety.

5 daily clinical assessments

health professionals evaluate your condition each day, recording scores that reflect organ function (SOFA score) and checking for signs of brain dysfunction (encephalopathy) using a standard questionnaire.

6 microbiological test on day 3

on the third day of antibiotic therapy a sample from your airway (tracheal aspiration) is taken.

the laboratory checks whether the bacteria that caused the infection are no longer present.

7 weekly screening for resistant bacteria

once a week, additional samples are collected to look for bacteria that have become resistant to the antibiotics.

this screening continues until day 28 or until you leave the intensive care unit.

8 clinical cure assessment at day 14

around the fourteenth day of your stay, clinicians determine whether you have achieved a clinical cure, meaning the infection signs have resolved.

if you are ready for discharge from the intensive care unit earlier, the assessment may be done sooner.

9 final follow‑up at day 28

on the twenty‑eighth day, the study records several outcomes, including the number of ICU free days (days you were alive and not in the intensive care unit), overall survival, and whether any additional antibiotics were needed.

the total number of days you received any antibiotic during the 28‑day period is also documented.

Who Can Join the Study?

Age 18 or older – you must be an adult.
Being cared for in the Intensive Care Unit (ICU), which is a special hospital area for very sick patients.
Having sepsis, which means your body is having a severe reaction to an infection.
Having a lab test that shows infection with Enterobacterales (a common group of bacteria) or non‑fermenting Gram‑negative bacilli (a type of bacteria that does not break down sugars in lab tests).
Currently receiving a beta‑lactam antibiotic (a family of antibiotics) such as cefotaxime, ceftazidime, cefepime, piperacillin, piperacillin‑tazobactam, meropenem, amoxicillin, or ceftazidime‑avibactam.
Providing informed consent yourself, or having a relative or legal representative give consent, or using the study’s emergency consent procedure.

Who Cannot Join the Study?

Having an allergy to beta-lactams (a common type of antibiotic) prevents participation.
Having a urinary infection (an infection of the bladder or kidneys) excludes you.
Having a plurimicrobial infection (an infection caused by more than one kind of germ) excludes you.
Having a “complex” infection such as a central nervous system infection (infection of the brain or spinal cord) or a bone or joint infection excludes you.
Being a protected person, which includes adults under legal guardianship or supervision, people who are imprisoned, pregnant women, women who are breastfeeding, or children, excludes you.
If doctors cannot measure the MIC (the lowest amount of antibiotic needed to stop bacterial growth) of the bacteria causing the infection, you cannot join.
Lacking coverage by a social security or health‑insurance scheme excludes you.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Centre Hospitalier Universitaire De Bordeaux	Bordeaux	France
Centre Hospitalier Universitaire De Lille	Lille	France
Centre Hospitalier Regional Et Universitaire De Brest	Brest	France

Other Sites

Site Name	City	Country
Centre Hospitalier Departemental Vendee	La Roche sur Yon	France
Centre Hospitalier Intercommunal De Cornouaille	Quimper	France
Groupe Hospitalier Rance Emeraude	Saint-Malo	France
Centre Hospitalier Universitaire d’Orléans	Orléans	France
Groupe Hospitalier Bretagne Sud	Lorient	France
Centre Hospitalier Bretagne Atlantique	Vannes	France
Centre Hospitalier Universitaire Amiens Picardie	Amiens	France
Centre Hospitalier Universitaire De Rennes	Rennes	France
Ajtxykhjcv Pfbglgaq Hvuyfgmm Dd Mhkihgnsw	Marseille	France
Cpkvkw Hflosylbbyb Rtybpfqe Umyppyeelwscd Db Tnydg	Tours	France
Clkd Dj Nyvgo	Vandoeuvre Les Nancy	France
Cepakb Huimiirrnpk Rnxixtsh Dxbpuzefdvrfbn	Angers	France
Cgfiuv Homntcsqplu Dl Sevddnawmlso	Saint-Brieuc	France

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	01.09.2026

Trial locations

Investigated Drugs:

Piperacillin is a beta‑lactam antibiotic that kills many types of bacteria. In the trial it is given by infusion to help treat serious infections caused by gram‑negative bacteria.

Tazobactam is a medicine that blocks enzymes some bacteria use to resist antibiotics. It is used together with piperacillin so the antibiotic can work better against resistant germs.

Amoxicillin is a penicillin‑type antibiotic that fights a wide range of bacterial infections. In the study it is given by infusion to treat patients with gram‑negative infections.

Cefotaxime belongs to the cephalosporin class of antibiotics. It has a broad spectrum of activity and is given by infusion to help clear serious gram‑negative bacterial infections.

Cefepime Dihydrochloride Monohydrate is a fourth‑generation cephalosporin antibiotic. It is strong against many gram‑negative bacteria, including those that are harder to treat, and is administered by infusion.

Ceftazidime is a cephalosporin antibiotic that works especially well against Pseudomonas and other gram‑negative germs. It is given by infusion as part of the treatment regimen.

Piperacillin Sodium is the sodium salt form of piperacillin, providing the same antibacterial action. It is infused to treat severe gram‑negative infections in the ICU.

Avibactam is a newer beta‑lactamase inhibitor that protects certain antibiotics from being broken down by resistant bacteria. In the trial it is combined with other drugs to improve their effectiveness.

Meropenem Trihydrate is a carbapenem antibiotic with very broad activity, used for infections that may not respond to other medicines. It is given by infusion to treat serious gram‑negative infections in critically ill patients.

BETARGET strategy is an individualized approach that uses therapeutic drug monitoring, measurement of the bacteria’s minimum inhibitory concentration, and computer‑based dose adjustments. This helps doctors give each patient the right amount of beta‑lactam antibiotic to improve outcomes.

Sepsis – Sepsis is a systemic response to infection that triggers widespread inflammation. The inflammatory response can cause blood pressure changes and impair the function of vital organs such as the lungs, kidneys, and liver. As the condition advances, organ dysfunction may become more pronounced, leading to the need for supportive care. Ongoing inflammation can result in further tissue damage and worsening of organ performance. Monitoring of clinical signs helps to track the evolution of the condition.

Trial ID:

2025-522819-42-01

Protocol code:

35RC23_8883_BETARGET

Trial Phase:

Human Pharmacology (Phase I) – Other

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Individualized beta‑lactam dosing with piperacillin (drug combination) for ICU patients with sepsis caused by gram‑negative bacteria

What is this study about?

Who Can Join the Study?

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