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Beta-lactams agents are time-dependent antibiotics. Their bactericidal effects are associated with the time spent above the minimal inhibitory concentration (MIC) of the bacteria. In ICU patients, many pathophysiological changes may occur, which significantly alter beta-lactam pharmacokinetics (increasing in distribution volume, hypoalbuminemia or change in glomerular filtration rate…), leading to antibiotic underexposure, which may explain some treatment failures and risk of emergence of a multi-resistant bacteria.
Many guidelines advocate to reach a fixed target for the steady-state free plasma concentration of beta-lactam between 4 and 8 times of the MIC. However, clinical evidences supporting that septic patients in ICU would benefit from such optimization remain low and contradictory, and use of surrogate MICs based on critical breakpoints instead of actual MICs are significant limitations in the description of beta-lactam exposure among ICU patients with sepsis.
In this study, the investigators aim to indentify profiles of intensive care unit patients which are more likely to be associated with pharmacological failure (< 4 time the MIC of the bacteria). The investigators also aim to identify association between failure and poor clinical outcome.
The duration of patient participation extends from the inclusion visit (D1), to discharge from intensive care; if the participant is still in intensive care at D90, the last visit with data collection will be at D90. The maximum duration of participation in the study will therefore be 3 months.
Taking into account 3 months of set-up, 1 year of recruitment, 3 months of participant follow-up, 3 months of data processing and 3 months of interpretation, 2 years will be sufficient to carry out this project.
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| Measure | Description | Time Frame |
|---|---|---|
| Identify proportion of participant with betalactam underexposure in critically ill patients with sepsis and predictive parameters. | Under-exposure to beta-lactam antibiotics is defined as a plasma concentration below 4x the MIC of the identified bacterium. This concentration will be measured as residual in the case of discontinuous administration, or at equilibrium in the case of continuous administration. This criterion is assessed between 48 and 72 hours after the start of antibiotic therapy. Variables that will be assessed include age (in years), body mass index (in kg/m²), renal clearance (calculated with creatininemia, urinary creatininuria urinary volumeper day expressed in mL/min), SAPSII score (no unit), site of infection, modality of antibiotic administration (intermittent, continuous), time since first antibiotic injection (in hours), body temperature (in °C), SOFA score (no units), blood cell numeration (in cell/mL), coagulation parameters (in % of activity), protidemia (in g/L), lactates level (in mmol/L). | 25 months |
| Measure | Description | Time Frame |
|---|---|---|
| Count the number of participants with poor clinical outcome and pharmacological failure (< 4 times the bacterial MIC). | The secondary objective is to establish the association between under-exposure to betalactam antibiotics in ICU participants and their clinical outcome. Pharmacological failure, defined as < 4 times the bacterial MIC, will be correlated with poor clinical outcome, up to and including death. |
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Inclusion Criteria:
Exclusion Criteria:
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Patients hospitalized in intensive care with sepsis.
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| Name | Affiliation | Role |
|---|---|---|
| Pierre FILLATRE | CENTRE HOSPITALIER SAINT-BRIEUC PAIMPOL TREGUIER REANIMATION | Principal Investigator |
| Nicolas NESSELER | CHU RENNES REANIMATION CHIRURGIE THORACIQUE CARDIAQUE ET VASCULAIRE | Study Chair |
| Yoann LAUNEY | CHU RENNES REANIMATION CHIRURGICALE | Study Chair |
| Flora DELAMAIRE | CHU RENNES REANIMATION MEDICALE | Study Chair |
| Guillaume RIEUL | CH BRETAGNE ATLANTIQUE REANIMATION | Study Chair |
| Pierre BOUJU | ch bretagne sud atlantique REANIMATION | Study Chair |
| Aurélien FREROU | CH ST MALO REANIMATION | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| FILLATRE | Saint-Brieuc | 22000 | France |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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Biological workup: hematological workup (CBC, platelets), blood urea, blood creatinine, urine urea, urine creatinine, blood gas, liver workup.
| 25 months |
| D013568 |
| Pathological Conditions, Signs and Symptoms |