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Sepsis is the major cause of morbidity and mortality amongst burn patients. Burn shock and respiratory failure that used to be the major cause of mortality have progressively been replaced by sepsis and multiple organ failure. It is not rare that treatment failures occurs several weeks, or even months after injury as a consequence of sepsis usually caused by multi-drug resistant (MDR) microorganisms. Introduction of early surgery combined with topical and systemic antibiotherapy dramatically enhanced survival from sepsis after burn trauma, but further improvement is impaired by the rapid development of hard-to-treat MDR bacteria.
Correct prescription of anti-infective agents could be one way to curb the steadily increasing development of multidrug resistance. Administration of antibiotic to burn patient is complex: they frequently suffer from kidney dysfunction, they usually experience tremendous shifts of liquids between intra-vascular - inter-cellular and intra-cellular compartments, they often are hypo-albumin and protein-emic, and finally they present with a profoundly modified metabolism. All those aspects make this particular population of patients at high risk of both under or over prescription.
Monitoring of drug concentrations in the plasma of patients, so-called TDM for Therapeutic Drug Monitoring, has been introduced to clinical practice for several decades primarily to avoid toxicity of a small number of drugs with narrow therapeutic windows. However, with the increasing availability of detection techniques, the number of drugs that can be measured in the plasma of patients has grown tremendously over the last decade. As a consequence, it is currently possible to monitor drug concentrations not only to prevent toxicity, but also to improve efficacy. For instance, several studies demonstrated that TDM improved antibiotic prescription in different populations of hospitalized patients, including critically ill patients, with a direct impact on outcome.
Such studies amongst burn patients are however lacking, although this particular population is at high risk to suffer from mis-prescription. We thus hypothesize that systematic TDM could improve antibiotic prescription in this peculiar population. To this end, we propose to implement a 3-year prospective, randomized, mono-centric, clinical trial that will analyze the impact of systematic TDM on anti-infective agent prescription amongst burned patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with systematic TDM of anti-infective agents | Experimental | Patients with systematic TDM of anti-infective agents and dosages adapted accordingly |
|
| Patients treated as usual | No Intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Systematic Therapeutic Drug Monitoring for the intervention group | Other |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time required to achieve anti-infective plasma concentrations in the target | Up to 3 years | |
| Numbers of concentrations within the target during an anti-infective agents course | Up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Anti-infective agents consumption | Up to 3 years | |
| Development of antibiotic resistance | Up to 3 years | |
| Length of ICU stay based on TBSA |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier Universitaire Vaudois | Lausanne | Canton of Vaud | 1011 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29914948 | Derived | Fournier A, Goutelle S, Que YA, Eggimann P, Pantet O, Sadeghipour F, Voirol P, Csajka C. Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center. Antimicrob Agents Chemother. 2018 Aug 27;62(9):e00505-18. doi: 10.1128/AAC.00505-18. Print 2018 Sep. | |
| 29263079 | Derived |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | May 1, 2018 | |
| Reset | Nov 30, 2018 | |
| Release | Dec 3, 2018 | |
| Reset | Mar 15, 2019 | |
| Release | Oct 1, 2019 | |
| Reset | Oct 23, 2019 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| May 1, 2018 | Nov 30, 2018 | |||
| Dec 3, 2018 |
| ID | Term |
|---|---|
| D002056 | Burns |
| ID | Term |
|---|---|
| D014947 | Wounds and Injuries |
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| Up to 3 years |
| Characterization of the pharmacokinetic profile of most widely used antibiotics | Up to 3 years |
| Concentration - efficacy analysis | Population pharmacokinetic (NONMEM software) | Up to 3 years |
| Failure / resolution rate of infectious episodes | Up to 3 years |
| Concentration - toxicity analysis | Population pharmacokinetic (NONMEM software) | Up to 3 years |
| Fournier A, Eggimann P, Pantet O, Pagani JL, Dupuis-Lozeron E, Pannatier A, Sadeghipour F, Voirol P, Que YA. Impact of Real-Time Therapeutic Drug Monitoring on the Prescription of Antibiotics in Burn Patients Requiring Admission to the Intensive Care Unit. Antimicrob Agents Chemother. 2018 Feb 23;62(3):e01818-17. doi: 10.1128/AAC.01818-17. Print 2018 Mar. |
| Mar 15, 2019 |
| Oct 1, 2019 | Oct 23, 2019 |