Plasma Concentrations of the Non-protein-bound Form of Vancomycin

University Hospital, Rouen77 enrolled

Overview

In routine practice, the use of vancomycin must be accompanied by plasma concentration monitoring to ensure that pharmacodynamic targets are met and that plasma concentrations are not in toxic ranges. Because vancomycin has high plasma protein binding and a free fraction exhibits marked inter-individual variability, this variability is increased in intensive care, monitoring is all the more imperative. The factors influencing the concentration and/or free fraction of vancomycin are numerous and vary from one study to another. The striking fact of this work is that the link between the concentration of the total form and the concentration of the free form has not been established. However, only plasma measurements of the total form of vancomycin are currently available to clinicians in routine practice, while only the free fraction is biologically active, responsible for its efficacy, but also for its toxicity in the event of an overdose. This paradox is widely highlighted by authors who have studied the free fraction of vancomycin, emphasizing the importance of continuing scientific research on this subject. Moreover, these studies are few in number, particularly in intensive care units, and their sample size is small, and they present biases, particularly those related to their essentially retrospective nature. The failure to consider the free concentration of vancomycin in the therapeutic monitoring strategy is primarily explained by the fact that clinicians do not have access to plasma concentrations of the free form of drugs in routine practice. Thus, the guidelines do not include pharmacodynamic targets for the free concentration, due to the lack of scientific data on the subject.

Since 2019, the Rouen University Hospital Pharmacology Laboratory has been measuring the non-protein-bound plasma concentrations of certain beta-lactam antibiotics. The analyzed sample comes from ultrafiltration of the plasma sample, a pre-analytical technique used in several studies on the free form of vancomycin. Access to this new technique at Rouen University Hospital gives us the opportunity to study free vancomycin concentrations in ICU patients. This study therefore aims to investigate free vancomycin plasma concentrations in patients admitted to the ICU treated for suspected or proven Gram-positive cocci infection, and for whom a dosage has been prescribed as part of routine practice. This prospective study aims to specifically analyze the concentration of the free form of vancomycin, but also to determine whether certain clinical or biological factors could predict this concentration. The long-term objective would be to be able to better individualize dosage regimens for vancomycin, a molecule with high inter-individual variability in intensive care patients, with the aim of reducing both underdoses, which are responsible for therapeutic failures, and overdoses, which are responsible for toxicity.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult patient hospitalized in intensive care, * Treated with vancomycin for a proven or suspected Gram-positive cocci infection, * For whom a plasma vancomycin dose has been prescribed * Patient who has been informed and has expressed verbal non-opposition. If the patient is unable to express their non-opposition (emergency situations), non-opposition must be obtained from the patient's representative, their trusted person, or, failing that, a relative. Exclusion Criteria: * Objection from the patient or their relatives * Discontinuous administration of vancomycin * Total plasma vancomycin levels measured 5 days or more prior to inclusion, with the plasma sample being stored in the laboratory for only 5 days, as is standard practice. * Individuals not covered by a social security scheme * Failure to perform the prescribed vancomycin dosage: discontinuation of vancomycin, death, etc. * Vancomycin serum sample taken before the 24th hour, including the loading dose.

Outcomes

Primary Outcomes

Measurement of plasma concentration of the free form of vancomycin

The primary endpoint is determined by the measurement of the plasma concentration of the free form of vancomycin during the total plasma concentration measurement after at least 24 hours of continuous infusion treatment.

Time frame: 24 hours after the start of continuous vancomycin infusion treatment

Secondary Outcomes

Measurement of the fraction of the non-protein-bound form of vancomycin in plasma

The fraction unbound to plasma proteins (free form) of vancomycin will be determined by the ratio of the concentration of the free form to that of the total form, and expressed as a %.

Time frame: 24 hours

To determine the areas under the 24-hour curve (AUC24h) for total plasma protein-bound forms of vancomycin

The area under the 24-hour plasma concentration curve (AUC24h) is calculated for vancomycin by the product of the plasma concentration times 24, due to continuous administration. It is expressed in mg.h/L.

Time frame: 24 hours

To compare the areas under the 24-hour curve (AUC24h) for total and non-plasma protein-bound forms of vancomycin

Time frame: 24 hours

To determine the areas under the 24-hour curve (AUC24h) for non-plasma protein-bound forms of vancomycin

Time frame: 24 hours

To assess the frequency of achieving vancomycin pharmacodynamic targets for its total plasma concentration

The pharmacodynamic objective of vancomycin will be considered to be achieved when the AUC24h/MIC of the total form is greater than or equal to 400, corresponding to a total vancomycinemia greater than 17 mg/L, for the treatment of a Staphylococcus sp with a MIC of 1 mg/L

Time frame: 24 hours

Plasma Concentrations of the Non-protein-bound Form of Vancomycin

Overview

Conditions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes