Therapeutic drug monitoring and virological response at week 48 in a cohort of HIV-1-infected patients switching to dolutegravir/rilpivirine dual maintenance therapy (ANRS-MIE-BIRIDER study).

AIMS: Dolutegravir (DTG) and rilpivirine (RPV) dual therapy is now recommended as a switch option in virologically suppressed HIV patients. Literature suggests that virological failure with dual therapy could possibly relate to subtherapeutic drug concentrations. In this study, we aimed at describing the DTG and RPV trough plasma concentrations (Cmin) and plasma HIV-1 RNA viral load (VL) during maintenance dual therapy. METHODS: We performed a retrospective analysis of DTG and RPV therapeutic drug monitoring in people living with HIV/AIDS (PLWHA) with dual therapy in 9 French centres. DTG and RPV trough plasma concentrations were estimated using a Bayesian approach to predict Cmin. The relationship between the pharmacokinetics of DTG and RPV and VL > 50 copies (cp)/mL was explored using joint nonlinear mixed models. The frequency of subtherapeutic threshold (DTG Cmin below 640 ng/mL and RPV Cmin below 50 ng/mL) were compared between PLWHA presenting VL > 50 cp/mL or not during the study. RESULTS: At baseline, 209 PLWHA were enrolled in the study. At week 48, 19 people living with HIV/AIDS (9.1%) discontinued their treatment and 15 PLWHA (7.1%) exhibited VL > 50 cp/mL. Six PLWHA out of 15 (40.0%) with VL > 50 cp/mL during the follow-up had at least 1 Cmin below the respective thresholds while only 26/194 patients (13.4%) without virological replication had at least 1 concentration below the threshold (P = .015). CONCLUSION: A majority of PLWHA receiving DTG/RPV maintenance dual therapy demonstrated VL < 50 cp/mL but virological replication was more frequent in people living with HIV/AIDS with subtherapeutic Cmin.

Assessment of Endocrine Disruptor Exposure in Hospital Professionals Using Hair and Urine Analyses: An Awareness Campaign.

BACKGROUND: In 2021, French public authorities initiated the fourth National Environmental Health Plan to prevent environment-related health risks. This plan primarily focuses on the sensitization of health professionals and health care institutions. Endocrine disruptors (EDs) are environmental factors associated with several adverse health effects, such as reproductive disorders, obesity, and cancer. This study aimed to conduct an awareness campaign among professionals at a general hospital center on the risks related to EDs. METHODS: Hospital professionals were directly involved in this study, and urine and hair samples were collected to determine bisphenol and paraben exposure levels. Analyses were performed using validated liquid chromatography-tandem mass spectrometry methods, enabling the simultaneous determination of bisphenols and parabens. A questionnaire on lifestyle habits was distributed to assess its relationship with the exposure profiles. Nineteen professionals were recruited for the study. RESULTS: Bisphenol A was detected in 95% of the urine samples, and the chlorinated derivatives of bisphenol A were between 16% and 63%. parabens showed detection frequencies between 37% and 100%, and methylparaben was quantified at an average concentration of 0.45 ± 0.46 ng/mL. In hair samples, bisphenols A, F, and S were detected at 95%-100%, chlorinated derivatives of bisphenol A were detected at 37%-68%, and parabens were detected at 100%. CONCLUSIONS: This awareness campaign may encourage health care institutions to adopt a policy of reducing endocrine disruptor exposure among their patients and professionals, who could be educated regarding the risks associated with EDs. Conducting a multicenter study to refine the results herein and establish a dynamic to prevent endocrine disruptor and environmental risks in health care systems would be valuable.

Quantification of the Conjugated Forms of Dichlorobisphenol A (3,3'-Cl 2 BPA) in Rat and Human Plasma Using HPLC-MS/MS.

BACKGROUND: Bisphenol A (BPA) is a ubiquitous contaminant that has endocrine-disrupting effects. Chlorinated derivatives of BPA are formed during chlorination of drinking water and have higher endocrine-disrupting activity. Dichlorobisphenol A (Cl 2 BPA) is the most abundant chlorinated BPA derivative found in several human biological matrices. Recent in vitro experiments have shown that Cl 2 BPA is metabolized in sulpho- and glucuro-conjugated compounds. To date, no assay has been developed to quantify the sulfo- and glucuro-conjugates of 3,3'-Cl 2 BPA (3,3'-Cl 2 BPA-S and 3,3'-Cl 2 BPA-G, respectively). METHODS: A high-performance liquid chromatography-tandem mass spectrometry assay for the determination of 3,3'-Cl 2 BPA conjugated forms in plasma samples was developed and validated according to the European Medicines Agency guidelines. Quantification was performed in the multiple reaction monitoring mode for all target analytes using a SCIEX 6500 + tandem mass spectrometer with an electrospray source operating in the negative ionization mode. Chromatographic separation was achieved using a C18 column maintained at 40°C and a binary mobile phase delivered in the gradient mode at a flow rate of 0.35 mL/min. Sample was prepared via simple precipitation using acetonitrile. The assay was validated and applied to rat and human plasma samples. RESULTS: Linearity was demonstrated over the range of 0.006-25 ng/mL for 3,3'-Cl 2 BPA-G and 0.391-100 ng/mL for 3,3'-Cl 2 BPA-S. Intraday and interday bias values were in the 95%-109% range, and the imprecision <9%. Internal standard corrected matrix effects were also investigated. This method enabled quantification of the conjugated forms of 3,3'-Cl 2 BPA in plasma samples. CONCLUSIONS: This is the first report on the development and validation of an analytical method for the quantification of 3,3'-Cl 2 BPA-G and 3,3'-Cl 2 BPA-S in the plasma matrix. This study is also the first report on the in vivo occurrence of these metabolites.

Analytical method for the biomonitoring of bisphenols and parabens by liquid chromatography coupled to tandem mass spectrometry in human hair.

Bisphenols and parabens are endocrine disruptors families widely used in daily life. They are known to be linked to numerous pathologies such as reproductive disorders, obesity, breast cancer, hypertension and asthma. Biomonitoring is an essential tool for assessing population exposure to environmental pollutants. Blood and urine are the main matrices used in human biomonitoring. However, they are not suitable to evaluate long-term exposure to endocrine disruptors with a short elimination half-life such as parabens or phenols. Hair appears to be an interesting alternative matrix allowing a wide window of exposure due to an accumulation of xenobiotics during hair growth. This study presents the development and validation of a high-performance liquid chromatography coupled to tandem mass spectrometry for the simultaneous determination of bisphenol A, its chlorinated derivatives, bisphenol F, bisphenol S and parabens in human hair. An optimised sample preparation based on acidic hydrolysis followed by liquid-liquid extraction was performed, before an analysis by ultra-high performance liquid chromatography coupled to tandem mass spectrometry in multiple reaction monitoring mode. To validate the method, recognized bioanalytical guidelines were used and calibration and quality control samples were prepared in human hair samples. Linearities were over 0.996 in the whole range of concentrations. Trueness and precision were demonstrated for each target analyte with intra-day and inter-day bias values ranging from 86 % to 118 % and relative standard deviation values ranging from 0 % to 19 %. At the same time, limits of quantification were set at 0.25 ng/g for bisphenol A and parabens, 0.05 ng/g for bisphenols F and S and 0.00625 ng/g for the chlorinated derivatives of bisphenol A. This reliable method was applied to hair samples taken from hospital professionals and allowed the quantification of these endocrine disruptors in this population. Chlorinated derivatives of bisphenol A were quantified here in hair for the first time.

Bisphenol A, Chlorinated Derivatives of Bisphenol A and Occurrence of Myocardial Infarction in Patients with Type 2 Diabetes: Nested Case-Control Studies in Two European Cohorts.

A positive association between Bisphenol A (BPA) exposure and coronary heart disease has been shown, but not in patients with type 2 diabetes (T2D). During the treatment of drinking water, chlorination leads to the formation of chlorinated derivatives of Bisphenol A (ClxBPA), that have higher estrogenic activity than BPA. No evidence exists for a relationship between exposure to ClxBPA and myocardial infarction in patients with T2D. The objective of this study was to evaluate the relationship between exposure to BPA, ClxBPA and the occurrence of myocardial infarction (MI) in patients with T2D. Two nested case-control studies in two independent European cohorts were performed. Each case with incident MI during follow-up was matched to one control on age, sex, and personal cardiovascular history in the same cohort. Association between baseline urine concentrations of BPA and of ClxBPA and incident MI was determined. Exposure to BPA was 31% in the ESTHER cohort and 18% in the SURDIAGENE cohort. In a meta-analysis of the two studies, occurrence of MI was significantly associated with urine BPA detection: adjusted OR = 1.97 (1.05-3.70), p = 0.04. Exposure to ClxBPA significantly differed in the SURDIAGENE and ESTHER studies: 24% and 8%, respectively (p = 0.0003). It was very strongly associated with MI in the SURDIAGENE cohort with an adjusted odds ratio (OR) of 14.15 (2.77-72.40) but this association was not replicated in the ESTHER study: adjusted OR: 0.17 (0.02-1.23). Whether these results may be explained by different water chlorination processes in France and Germany, resulting in different ClxBPA exposure levels, requires further investigation.

Population pharmacokinetics of teicoplanin administered by subcutaneous or intravenous route and simulation of optimal loading dose regimen.

Objectives: To investigate the population pharmacokinetics of teicoplanin in patients treated by the subcutaneous (sc) and/or intravenous (iv) route. Patients and methods: Non-linear mixed-effects modelling described teicoplanin concentrations from 98 patients with infection caused by Gram-positive cocci. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) of various dosage regimens. Results: Teicoplanin concentrations were best described by a two-compartment model with clearance predicted by estimated glomerular filtration rate. Estimated absorption rate constant (between-subject variability) was 0.039 h-1 (77%), clearance was 0.305 L/h (28%), central volume was 10.3 L (49%), inter-compartmental clearance was 4.42 L/h (66%) and peripheral volume was 97.4 L (51%). The sc route was associated with lower initial Cmin and AUC (day 3: loading phase) compared with the iv route. This difference appeared to vanish after 14 days, with comparable simulated PTAs based on the Cmin and AUC for all tested dosages (400, 600, 800 and 1000 mg every 12 h). However, a loading dose regimen with five administrations of either 400 or 600 mg was not sufficient to achieve the target Cmin (≥15 mg/L) for both routes. Also, PTAs for higher MIC (≥1.0 mg/L) were poor with all regimens for both routes. Conclusions: This is the first study examining the pharmacokinetic/pharmacodynamic implications of using the sc route for teicoplanin. Subcutaneous administration is associated with lower Cmin and AUC values after the loading phase compared with iv administration. Therefore, iv administration should be preferred in the first few days of therapy. This study also shows that loading doses of teicoplanin higher than currently recommended should be used to improve PTA.

Ultrasensitive determination of bisphenol A and its chlorinated derivatives in urine using a high-throughput UPLC-MS/MS method.

Bisphenol A (BPA) is a well-known endocrine disruptor. Chlorinated derivatives of BPA (ClxBPA) may be formed by reaction of chlorine with BPA present in drinking water. ClxBPA exhibit a higher level of estrogenic activity than BPA. While many studies have reported detectable BPA concentrations in urine, only very few studies were conducted in regards to ClxBPA. Since ClxBPA are potentially more toxic, it is important to assess large-scale exposure of the general population. Indeed, in the field of environment health, large studies are required to assess exposure to pollutants at ultratrace concentrations; therefore, analytical methods have to be rapid and sensitive. This work intends to validate a highly sensitive and rapid analytical method suitable to evaluate BPA and ClxBPA exposures during large-scale biomonitoring studies. For that purpose, a method based on online solid-phase extraction coupled with isotope dilution ultrahigh - performance liquid chromatography-tandem mass spectrometry was developed and validated according to accepted guidelines. The matrix-matched calibration curve ranged from 0.25 to 16.0 ng mL(-1) and from 0.025 to 1.60 ng mL(-1) for BPA and ClxBPA, respectively. This method was precise (the intra- and inter-day coefficients of variation of quality control were <16.4%) and accurate (bias ranged from -4.0 to 16.8%). The limit of quantification was validated at 0.25 and 0.025 ng mL(-1), for BPA and ClxBPA, respectively. The limit of detection was estimated for each experiment performed. Finally, this method is rapid and sensitive enough to be carried out during biomonitoring studies of BPA and ClxBPA in human urine.

Analytical methods and biomonitoring results in hair for the assessment of exposure to endocrine-disrupting chemicals: A literature review.

Endocrine-disrupting chemicals (EDC) are compounds that alter functions of the endocrine system due to their ability to mimic or antagonize endogenous hormones, or that alter their synthesis and metabolism, causing adverse health effects. Human biomonitoring (HBM) is a reliable method to assess human exposure to chemicals through measurement in human body fluids and tissues. It identifies new sources of exposure and determines their distribution, thereby enabling detection of the most exposed populations. Blood and urine are commonly used for HBM of EDC, but their interest is limited for compounds presenting short half-lives. Hair appears as an interesting alternative insofar as it provides a large exposure window. For the present study, we evaluated the relevance of hair in determining EDC exposure. With this in mind, we undertook a literature review focusing on the bioanalytical aspects and performances of methods developed to determine EDC in hair. The literature review was performed through methodical bibliographical research. Relevant articles were identified using two scientific databases: PubMed and Web of Science, with search equations built from a combination of keywords, MeSH terms and Boolean operators. The search strategy identified 2949 articles. After duplicates were removed, and following title, abstract, and full-text screenings, only 31 were included for qualitative synthesis. Hair collection was mainly performed in the back of the head and preparation involved two processes: cutting into small pieces or grounding to powder. The off-line LC-MS/MS method remains the main technique used to assess EDC through hair. Differences regarding the validation of analytical methods and interpretation of HBM results were highlighted, suggesting a need for international harmonisation to obtain reliable and comparable results. External contamination of hair was identified as a main limitation in the interpretation of results, highlighting the need to better understand EDC transfers through hair and to develop relevant hair decontamination processes.

N-Ethylhexedrone: A very long and bad trip! A case series.

N-ethylhexedrone (NEH) is a new cathinone derivative with, currently, low toxicokinetic and toxicodynamic knowledge. We present three documented clinical cases of NEH intoxication with plasma and urine concentrations. A thorough search for metabolites was performed. The three patients were admitted to the emergency department, and two out of the three were hospitalized for an extended period. While recovering from the drug effects, 12-24 h after nasal intake of New Psychoactive Substance (NPS), the patients described the following disorders: anxiety, feelings of persecution, asthenia, anhedonia, abulia, psychomotor slowing and loss of consciousness. NEH was identified in all samples by liquid chromatography-high resolution mass spectrometry (LC-HRMS), and quantified by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). Quantitative analysis showed decreasing concentrations over time: for Case 1, from 97.2 (Day 1, D1) to 0.7 (Day 7, D7) µg/L for plasma, and from 724 (D1) to 0.5 (D7) µg/L for urine. NEH concentration of 7.9 µg/L was found in the plasma collected at admission for Case 2. For Case 3, concentrations ranging from 49 (D1) to 1.8 (D7) µg/L in plasma, and from 327.3 (Day 6, D6) to 116.8 (D7) µg/L in urine were found. NEH was no longer detected in the urine sample at Day 10. Elimination half-life was estimated at 19, and 28 hours in Patients 1 and 3, respectively. Four metabolites were identified in blood and urine: reduced NEH, dealkyl-NEH, reduced dealkyl-NEH and hydroxy-NEH. The cases presented highlight the long detectable lifetime of NEH. Characterization of the metabolites will allow better identification of the consumption of this drug. Serious adverse events can be observed after NEH consumption, as two out of the three patients required intubation and ventilation. A syndrome of inappropriate antidiuretic hormone secretion (SIADH) was also diagnosed. Two out of the three cases are notable because of the number of samples collected and because NEH was the only drug of abuse detected.

Gentamicin in hemodialyzed critical care patients: early dialysis after administration of a high dose should be considered.

Gentamicin is a widely used antibiotic in the intensive care unit (ICU). Its dosage is difficult to adapt to hemodialyzed ICU patients. The FDA-approved regimen consists of the administration of 1 to 1.7 mg/kg of gentamicin at the end of each dialysis session. Better pharmacokinetic management could be obtained if gentamicin were administered just before the dialysis session. We performed Monte Carlo simulations (MCS) to determine the best gentamicin pharmacokinetic profile (high peak and low trough concentrations). Then, 6 mg/kg of gentamicin was infused into 10 ICU patients over a period of 30 min. A 4-h-long hemodialysis session was started 30 min after the end of the infusion. Pharmacokinetic samples were regularly collected over 24 h. A one-compartment model with zero-order input and first-order elimination was developed in Nonmem version VI to analyze patients' measured gentamicin concentration-versus-time profiles. Finally, additional MCS were performed to compare the regimen chosen with the FDA-approved gentamicin regimen. High peak concentrations (C(max), 31.8 ± 16.8 mg/liter) were achieved. The estimated C(24) and C(48) values (concentrations 24 and 48 h, respectively, after the beginning of the infusion) were 4.1 ± 2.3 and 1.8 ± 1.2 mg/liter, respectively. The volume of distribution was 0.21 ± 0.06 liter/kg. MCS confirmed that the dosing regimen chosen achieved the target C(max) whereas the FDA-approved regimen did not (31.0 ± 10.9 versus 8.8 ± 3.1 mg · liter(-1)). Moreover, the C(24) values were similar while the AUC(0-24) values were moderately increased (190.8 ± 65.0 versus 135 ± 42.2 mg · h · liter(-1)). Therefore, administration of 6 mg/kg of gentamicin before hemodialysis to critically ill patients achieves a high C(max) and an acceptable AUC, maximizing pharmacokinetic/pharmacodynamic endpoints.

In vitro reciprocal interactions between yeasts from human cutaneous mycobiota and parabens used in cosmetics.

Parabens are substances with antifungal and antibacterial properties, suspected to be endocrine disruptors and widely used as preservatives in cosmetics. In this case, exposure to these compounds is mainly dermal and interactions may occur with skin components including cutaneous mycobiota. In this work, we have explored the in vitro reciprocal interactions between three parabens (methylparaben, ethylparaben, and propylparaben) and yeasts from the human cutaneous mycobiota (Candida parapsilosis, Cryptococcus uniguttulatus, and Rhodotorula mucilaginosa) by studying the effect of these parabens on fungal growth and the fungal ability to metabolize the tested compounds. Our results showed that, at the tested concentrations, the growth of three strains of C. parapsilosis was not influenced by the presence of parabens. Whereas, using the same parabens concentrations, growth of C. uniguttulatus and R. mucilaginosa was completely inhibited by ethylparaben since the first day of contact, whereas these same fungi were not sensitive to the two other parabens, even after seven days of incubation. The presence of a lamellar wall in these basidiomycete fungi as well as the physico-chemical properties of ethylparaben could explain this selective inhibition. Additionally, C. parapsilosis and R. mucilaginosa degraded 90% to 100% of propylparaben after seven days of incubation but had no effect on the other tested parabens. Thus, their enzymes seem to only degrade long chain parabens. In the same conditions, C. uniguttulatus did not degrade any paraben. This inability may be due to the absence of fungal enzymes able to degrade parabens or to the possible inaccessibility of intracellular enzymes due to the polysaccharide capsule. Our work has shown that parabens can act differently from one fungus to another within the cutaneous mycobiota. These preliminary results have evidenced that in vitro parabens, contained in cosmetic products, could be involved in the occurrence of a state of dysbiosis. The tested yeasts from the cutaneous mycobiota can also be involved in the degradation of parabens and thereby reduce, according to the produced metabolites and their activities, the risk of endocrine disruption they can induce.

Exposure to endocrine disruptors promotes biofilm formation and contributes to increased virulence of Pseudomonas aeruginosa.

Anthropogenic activities contribute to the spread of chemicals considered as endocrine disruptors (ED) in freshwater ecosystems. While several studies have reported interactions of EDs with organisms in those ecosystems, very few have assessed the effect of these compounds on pathogenic bacteria. Here we have evaluated the impact of five EDs found in aquatic resources on the virulence of human pathogen P. aeruginosa. ED concentrations in French aquatic resources of bisphenol A (BPA), dibutyl phthalate (DBP), ethylparaben (EP), methylparaben (MP) and triclosan (TCS) at mean molar concentration were 1.13, 3.58, 0.53, 0.69, and 0.81 nM respectively. No impact on bacterial growth was observed at EDs highest tested concentration. Swimming motility of P. aeruginosa decreased to 28.4% when exposed to EP at 100 µM. Swarming motility increased, with MP at 1 nM, 10 and 100 µM (1.5-fold); conversely, a decrease of 78.5%, with DBP at 100 µM was observed. Furthermore, exposure to 1 nM BPA, DBP and EP increased biofilm formation. P. aeruginosa adhesion to lung cells was two-fold higher upon exposure to 1 nM EP. We demonstrate that ED exposure may simultaneously decrease mobility and increase cell adhesion and biofilm formation, which may promote colonisation and establishment of the pathogen.

Characterization of pregnant women exposure to halogenated parabens and bisphenols through water consumption.

Exposure of pregnant women to endocrine disruptor compounds, such as parabens and bisphenol A is of concern for fetal transition. Their halogenated degradation products, mainly coming from water treatment plans, could be problematic as well, depending on their occurrence in drinking water in the first place. Thus, 25 halogenated compounds were synthesised in order to investigate 60 substances (Bisphenols, parabens and their degradation products) in 325 drinking water samples coming from a French cohort study of pregnant women. Analysis was performed by tandem mass spectrometry coupled to gas chromatography (GC-MS/MS) after SPE extraction and derivation of the contaminants. Results indicate that parabens (methylparaben, n-propylparaben, ethylparaben and n-butylparaben), bisphenols S, A and F, and their degradation product, 4-hydroxybenzoic acid, were detected up to several hundred ng/L in drinking water, with detection frequencies between 16% and 88%. Regarding halogenated degradation products, the highest detection frequencies were found for monochlorinated products (about 50% for 2-chlorobisphenol A), which were quantified up to several tens of ng/L. Such analytical approaches with broader spectrum of monitoring (i.e. chemical hazards and their degradation products) constitute in the beginning of a solution to exhaustively answer the questions related to the characterization of the human chemical exposome.

[Level of evidence for therapeutic drug monitoring of aminoglycosides]. / Niveau de preuve du suivi thérapeutique pharmacologique des aminosides.

Aminoglycosides are major antibiotics indicated for the treatment of infection with gram-negative bacilli. They are characterized by high clinical effectiveness but their main drawback is the occurrence of toxicity in a significant number of patients. Pharmacokinetic parameters of aminoglycosides exhibit wide inter-individual variability and the relationships between concentration and effect have been clearly demonstrated. Consistent studies have demonstrated that therapeutic drug monitoring (TDM) of aminoglycosides administered in multiple daily doses was cost-effective in maximising antibiotic efficacy and/or reducing incidence of toxicity. Therefore TDM of aminoglycosides should be considered "essential". Level of evidence for TDM of aminoglycosides administered once daily is not so clearly demonstrated however it should be highly recommended.

[Not Available]. / Niveau de preuve du suivi thérapeutique pharmacologique des aminosides.

Aminoglycosides are major antibiotics indicated for the treatment of infection with gram-negative bacilli. They are characterized by high clinical effectiveness but their main drawback is the occurrence of toxicity in a significant number of patients. Pharmacokinetic parameters of aminoglycosides exhibit wide inter-individual variability and the relationships between concentration and effect have been clearly demonstrated. Consistent studies have demonstrated that therapeutic drug monitoring (TDM) of aminoglycosides administered in multiple daily doses was cost-effective in maximising antibiotic efficacy and/or reducing incidence of toxicity. Therefore TDM of aminoglycosides should be considered "essential". Level of evidence for TDM of aminoglycosides administered once daily is not so clearly demonstrated however it should be highly recommended.

[Level of evidence for therapeutic drug monitoring of fluconazole]. / Niveau de preuve du suivi thérapeutique pharmacologique du fluconazole.

Fluconazole is a recommended treatment option for the treatment of invasive candidiasis. Fluconazole is active against most pathogenic Candida spp. except C. kruzei and C. glabrata. Fluconazole is orally well absorbed. Its volume of distribution is reported to be 0.7-1.0 L/kg and it is weakly bound to plasma proteins. The majority of fluconazole dose is excreted via the kidneys. Usually, fluconazole pharmacokinetics display moderate inter-individual variability. However, in presence of renal dysfunction or in pediatrics patients, fluconazole pharmacokinetics might be difficult to predict. Concentration-efficacy relationships are demonstrated whereas concentration-toxicity relationships are sparse. As a consequence, therapeutic drug monitoring is not routinely recommended but can be useful in certain situations.

[Level of evidence for therapeutic drug monitoring of teicoplatin]. / Niveau de preuve du suivi thérapeutique pharmacologique de la teicoplanine.

Teicoplanin is a glycopeptid antibiotic used for treatment of serious infections caused by Gram+ bacteriae. The treatment scheme corresponds to an initial loading dose followed by maintenance dose. High interindividual pharmacokinetic variability and strong relation between high through concentrations, dose and clinical success, support the need of therapeutic drug monitoring using through concentrations. Achieving through concentrations ≥ 10-15 mg/L or ≥ 20-40 mg/L, regarding the measurement method and the infection severity, is recommended to increase clinical success rate. The level of proof of therapeutic drug monitoring is evaluated: "necessary".