Impact of Therapeutic Drug Monitoring on Anti-Infective Agents Amongst Severely Burned Patients Requiring ICU Admission

Study Overview
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Brief Summary
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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 Burn shock and respiratory failure that used to be the major cause of mortality have progressively been replaced by sepsis and multiple organ failure.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.

Conditions
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Burn

Intervention / Treatment
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* Other: Systematic Therapeutic Drug Monitoring for the intervention group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All adult burn patients (≥ 18 years) admitted to the University Hospital of Lausanne during the study period receiving systemic anti-infectives agents for which TDM is available will be included. Exclusion Criteria: Patients not receiving systemic anti-infective agents therapy Patients with length of hospital stay <72 hours Patients refusing to give their written consent (or for which the therapeutic representative refuses) or incapable of understanding and lack of legal representative Pregnant or breastfeeding women Children <18 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with systematic TDM of anti-infective agents<br>Patients with systematic TDM of anti-infective agents and dosages adapted accordingly | Other: Systematic Therapeutic Drug Monitoring for the intervention group<br> <br> |
| No Intervention: Patients treated as usual<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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patients