Influence of pharmacokinetic/pharmacodynamic ratio on vancomycin treatment response in pediatric patients with Staphylococcus aureus bacteremia.

BACKGROUND: Staphylococcus aureus is a frequent cause of hospital-acquired bacteremia in pediatric patients. Vancomycin is the drug of choice for the treatment of methicillin-resistant strains, although treatment failure is frequently observed. Area under the curve (AUC) of plasma concentrations over the minimum inhibitory concentration (MIC) has been proposed as the best index to predict treatment response, although information about its clinical impact on pediatric patients is scarce. The objective of this study is to determine if early recovery of an AUC/MIC>400 mg*h/L for vancomycin in pediatric patients with S. aureus bacteremia is associated with clinical and microbiological treatment response. METHODS: Retrospective observational study. Pediatric patients younger than 3 years with vancomycin-treated S. aureus bacteremia were included. The pharmacokinetic parameters were calculated from the vancomycin value obtained in the first 72 hours of treatment, assuming a bicompartmental model. A multivariate analysis was performed to analyze factors associated with early clinical response, treatment failure, microbiological response and 30-day mortality. RESULTS: Fifty-one patients with S. aureus bacteremia were included in the study. In 18 patients (35.3%), strains with a MIC higher than 1.0 mg/L were isolated, being in eight (15.7%) greater than 1.5 mg/L. 22 (43.1%) patients did not reach an estimated AUC/MIC>400 during the first 72 hours. A significant association was observed between attainment of an AUC/MIC>400 and early clinical response (OR:3.23 [95% CI: 1.07-12.03]). No significant association was found between an AUC/MIC>400 and microbiological response or mortality. CONCLUSIONS: An AUC/MIC>400 is associated with early response to vancomycin in pediatric patients with S. aureus bacteremia.

Pre and post intervention study of antiblastic drugs contamination surface levels at a Pharmacy Department Compounding Area using a closed system drug transfer device and a decontamination process.

Assuring healthcare workers security on Hazardous Drugs (HD) compounding is critical in healthcare settings. Our study aims to demonstrate that the use of a Close System drug Transfer Device (CSTD) PhaSeal™ added to a decontamination process reduces antiblastic surface contamination levels in the Compounding Area (CA) of our Pharmacy Department (PD). We selected cyclophosphamide, 5-fluorouracil and iphosphamide to be evaluated. Testing was carried out with a wipe kit and quantified by an independent laboratory. We defined four sampling times: baseline; just after a decontamination procedure, which was repeated weekly during the study; four months after introduction of CSTD PhaSeal™ for cyclophosphamide and 5-fluorouracil compounding; and after eight months using CSTD PhaSeal™ for cyclophosphamide and 5-fluorouracil and one month for iphosphamide compounding. There was a decrease at the number of positive samples at the beginning/end of the study for all the drugs tested: 28/15 for cyclophosphide, 29/23 for iphosphamide and 7/1 for 5-fluorouracile. Comparing to the baseline, median cyclophosphamide levels significantly decreased (p-value <0.001) at 4 and 8 months sampling time (baseline: 1.01 ng/cm2 to 0.06 ng/cm2 and 0.01 ng/cm2), and median iphosphamide levels significantly decreased (p < 0.001) at 8 months sampling time (baseline: 3.02 ng/cm2 to 0.06 ng/cm2). 5-Fluorouracil did not show significant differences between the sampling times (baseline: 0.09 ng/cm2 to 0.09 ng/cm2). We saw a significant increase at iphosphamide levels at 4 months sampling point, contrary to cyclophosphamide, which levels had decreased. The use of CSTD PhaSeal™ for iphosphamide compounding the last month was implemented for ethical reasons after this intermediate results review. Our study suggests that the use of CSTD PhaSeal™, adding to decontaminating procedures, significantly reduces antiblastic drug surface levels at the CA of our PD.

Effect of the dietary intake of melatonin- and hydroxytyrosol-rich wines by healthy female volunteers on the systemic lipidomic-related oxylipins.

Oxylipins are lipid mediators involved in the physiopathology of all organs. Moreover, isoprostanes have been established as general and reliable in vivo oxidative stress biomarkers. Red wine has proved to exert several benefits through the maintenance of the oxidative balance of the organism. Antiradical scavenging capacity has been mainly attributed to polyphenols. However, melatonin and hydroxytyrosol should be taken into account as potent antiradical agents. The present research aimed to clarify the situation of enzymatic and oxidative injury and eicosanoid urinary excretion related to the intake of three kinds of red wines and their primary musts. Judging by the reduction in the excretion of isoprostanes, red wine consumption exhibited the highest antioxidant protection against oxidative stress, attributed to its OHTyr content (p < 0.05), and to a lesser extent to its MEL content. Similarly, the intake of red wine leads to the cardioprotective effect due to the reduction in the urinary excretion of the pro-inflammatory prostaglandin 2,3-dinor-11-ß-PGF2α, besides the increase in the vasodilator prostaglandin PGE1, mediated by the melatonin (p < 0.05) and hydroxytyrosol (p < 0.05) contents. In conclusion, red wine (especially non-aged wine) exerts a higher in vivo antioxidant capacity than must or alcohol.