Skin protection creams in medical settings: successful or evil?

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Modelled target attainment after temocillin treatment in severe pneumonia: systemic and epithelial lining fluid pharmacokinetics of continuous versus intermittent infusions.

Objectives: To describe the population pharmacokinetics of temocillin administered via continuous versus intermittent infusion in critically ill patients with pneumonia. Secondary objectives included characterization of epithelial lining fluid (ELF)/plasma penetration ratios and determination of the probability of target attainment (PTA) for a range of MICs. Methods: Thirty-two mechanically ventilated patients who were treated for pneumonia with 6g of temocillin daily for in vitro sensitive pathogens were assigned either to the II (2g every 8h over 0.5h) or to the CI (6g over 24h after a loading dose of 2g) group. A population pharmacokinetic model was developed using unbound plasma and total ELF concentrations of temocillin and related Monte Carlo simulations were performed to assess PTAs. Results: The AUC(0-24) ELF/plasma penetration ratio was 0.73, at steady-state, for both modes of infusion and whatever the level of creatinine clearance. Monte Carlo simulations showed for the minimal pharmacodynamic (PD) targets of 50% T> 1X MIC (II group) and 100% T > 1X MIC (CI group), PK/PD breakpoints of 4 mg/L in plasma and 2 mg/L in ELF and 4mg/L in plasma and ELF, respectively. The breakpoint was 8 mg/L in ELF for both modes of infusion in patients with CL(CR)<60mL/min. Conclusion: While CI provides better PKPD indexes, the latter remain below available recommendations for systemic infections, except in case of moderate renal impairment, thereby warranting future clinical studies in order to determine the efficacy of temocillin in severe pneumonia

Validation of an UHPLC/DAD method for the determination of cannabinoids in seized materials: Analysis of 213 samples sold in Belgian CBD shops

Purpose: Nowadays, (−)-cannabidiol (CBD) is gaining popularity for the treatment of various problems and can be found easily in many stores in Belgium. However, such product must comply with the law: if the total tetrahydrocannabinol (THC) content [(−)-Δ9-tetrahydrocannabinol + (−)-Δ9-tetrahydrocannabinolic acid A (THC-A)] is higher than 0.2%, it is considered as narcotic by the Belgian legislation. In this context, we have developed a method to quantify major cannabinoids (THC, THC-A, CBD, cannabidiolic acid, cannabigerolic acid, cannabigerol and cannabinol) in plant material. Methods: After drying, a liquid-liquid extraction was performed on plant materials, followed by dilutions. Extracts were analyzed by ultra-high-performance liquid chromatography combined with a photodiode array detector. Mobile phases consisted of methanol and 0.1% formic acid in water applied in a 16-minute gradient mode. After validating the method, it was applied to 213 samples seized by the police in CBD shops. Results: The method fulfilled the criteria in terms of specificity, calibration curve, precision, trueness and dosing range. Total THC content ranged from 0.14 to 1.17% (median 0.38%) with 110 samples exceeding the Belgian legal threshold of 0.2%. The amounts measured in the samples varied greatly, some were 6 times below the amount labelled on the packaging, others showed a concentration 4 times higher than stated on the package. Same strain also showed concentration differences from shop to shop. Conclusion: Our method was successfully validated and applied to samples seized in CBD shops. Half of the products exceeded the Belgian legal threshold. THC and CBD concentrations discrepancies showed that products sold in CBD shops are not pharmaceutical grade. © 2020 Elsevier B.V

Application de la résonance magnétique nucléaire (RMN) en toxicologie judiciaire

peer reviewe

Continuous infusion of cefepime and neurotoxicity: a retrospective cohort study.

peer reviewedObjectives: Neurotoxicity related to cefepime is increasingly reported in the literature but specific data concerning continuous infusion (CI) of the drug are still lacking. Our primary objective was to evaluate the incidence of neurotoxicity related to CI of cefepime and the associated risk factors. Our secondary objectives were to analyse the plasma cefepime concentrations and to define the threshold above which neurotoxicity occurs. Methods: In this single-centre retrospective cohort study, all adult patients who underwent at least one cefepime therapeutic drug monitoring (TDM) and were treated with CI of 4 g/day between January 2017 and June 2019 were included. Neurotoxicity was evaluated according to a strict definition and was correlated with steady-state concentration at the time of toxicity presentation. Results: Ninety-eight patients with 201 cefepime TDM studies were included, with an incidence of neurotoxicity of 14.3% (14/98). Patients with neurotoxicity had more often underlying brain disease (35.7% (5/14) vs 11.9% (10/84), p = 0.030)) and higher steady-state concentrations (mean ± standard deviation 71.8 ± 32.9 mg/L vs 49.6 ± 30.6, p = 0.036) than the others. A receiver operating characteristic curve analysis yielded a cefepime steady-state concentration of 63.2 mg/L as the best cut-off point between patients with or without neurotoxicity. A mean steady-state concentration of 46.4 mg/L was achieved if the dosages of cefepime were adapted to renal function which was under our threshold concentration but above our highest pharmacokinetic/pharmacodynamic target of 32-40 mg/L. Conclusions: Our results suggest that 4 g/day of cefepime adapted to renal function and infused over 24 h is a trade-off for the risk/benefit ratio, when used empirically

Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study

OBJECTIVES: The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia. PATIENTS AND METHODS: Among 55 patients in intensive care treated with 1 g of meropenem every 8 h for severe nosocomial pneumonia, 30 were assigned to intermittent infusion (II; over 0.5 h) and 25 to extended infusion (EI; over 3 h) groups. Based on plasma and epithelial lining fluid (ELF) concentrations determined at steady-state, pharmacokinetic modelling and Monte Carlo simulations were undertaken to assess the probability of attaining drug concentrations above the MIC for 40%-100% of the time between doses (%T > 1-fold and 4-fold MIC), for 1 or 2 g administered by either method. RESULTS: Penetration ratio, measured by the ELF/plasma ratio of AUCs, was statistically higher in the EI group than in the II group (mean ± SEM: 0.29 ± 0.030 versus 0.20 ± 0.033, P = 0.047). Considering a maximum susceptibility breakpoint of 2 mg/L, all dosages and modes of infusions achieved 40%-100% T > 1-fold MIC in plasma, but none did so in ELF, and only the 2 g dose over EI achieved 40%-100% T > 4-fold MIC in plasma. CONCLUSIONS: The optimum regimen to treat severe nosocomial pneumonia was 2 g of meropenem infused over 3 h every 8 h. This regimen achieved the highest pharmacodynamic targets both in plasma and in ELF

Technique d'extraction de 12 benzodiazépines dans le plasma. Résultats expérimentaux multicentriques

Dans le cadre des différents thèmes de travail proposés aux membres de la commission de Toxicologie Clinique de la SFTA, une étude est réalisée sur l'identification et la quantification simultanée de 12 benzodiazépines dans le plasma. L'objectif est de tester la robustesse d'une technique d'extraction en l'imposant aux différents participants, les conditions chromatographiques de séparation et le mode de détection restant libres, fonctions de l'équipement de chaque laboratoire. L'étude a été réalisée sur une période de 2 mois et demi. Deux échantillons tests de plasmas surchargés avec 12 benzodiazépines à des concentrations thérapeutiques ou supra-thérapeutiques sont adressés à chaque centre d'investigation en vue de leur évaluation. La technique d'extraction utilise un mélange d'hexane / dichlorométhane en milieu tamponné (pH 9.2) et le loflazépate d'éthyle comme standard interne. Une méthode CLHP avec détecteur à barrette de diode est proposée à défaut par le laboratoire coordonnateur aux participants ne disposant pas de technique d'analyse. Sur les 11 participants, 10 utilisent une technique CLHP, un seul une technique CPG. Parmi les techniques CLHP, 2 d'entre elles associent un détecteur de masse, 7 un détecteur à barrette de diodes, 1 un détecteur UV. La technique CPG est associée à un détecteur de masse. L'analyse des résultats montre que la technique d'extraction proposée a été testée avec succès par 8/11 des participants : 4/11 laboratoires sans erreur et 4/11 laboratoires avec 1 ou 2 résultats exclus. Par contre, 3/11 laboratoires ont rencontré des difficultés majeures : un site par la survenue d'émulsions lors du traitement des échantillons tests (plasmas lyophilisés à reconstituer), un site par manque de temps et d'expérience, le troisième mettant en cause le choix du standard interne en technique CPG, le loflazépate d'éthyle n'ayant pas fait l'objet d'une étude préalable par cette technique