Superiority of ceftazidime off-label high-dose regimen in PK/PD target attainment during treatment of extensively drug-resistant Pseudomonas aeruginosa infections in cancer patients.

AIM: The objective of this study was to evaluate off-label high-dose ceftazidime population pharmacokinetics in cancer patients with suspected or proven extensively drug-resistant (XDR) Pseudomonas aeruginosa infections and then to compare the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target after standard and off-label high-dose regimens using population model-based simulations. A further aim was to clinically observe the occurrence of adverse effects during the off-label high-dose ceftazidime treatment. METHODS: In patients treated with off-label high-dose ceftazidime (3 g every 6 h), blood samples were collected and ceftazidime serum levels measured using LC-MS/MS. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were then used to compare standard and high-dose regimens for PK/PD target attainment. RESULTS: A total of 14 cancer patients with serious infection suspected of XDR P. aeruginosa aetiology were eligible for PK analysis. XDR P. aeruginosa was confirmed in 10 patients as the causative pathogen. Population ceftazidime volume of distribution was 13.23 L, while clearance started at the baseline of 1.48 L/h and increased by 0.0076 L/h with each 1 mL/min/1.73 m2 of eGFR. High-dose regimen showed significantly higher probability of target attainment (i.e., 86% vs. 56% at MIC of 32 mg/L). This was translated into a very low mortality rate of 20%. Only one case of reversible neurological impairment was observed. CONCLUSION: We proved the superiority of the ceftazidime off-label high-dose regimen in PK/PD target attainment with very low occurrence of adverse effects. The off-label high-dose regimen should be used to optimize treatment of XDR P. aeruginosa infections.

Comparison of Polyphenol-Enriched Tomato Juice and Standard Tomato Juice for Cardiovascular Benefits in Subjects with Stage 1 Hypertension: a Randomized Controlled Study.

There is a growing body of evidence that tomato consumption reduces the risk of cardiovascular disease, through antioxidative, anti-inflammatory and hypotensive effects. We compared the effects of polyphenol-enriched and standard tomato juice on parameters of lipid and oxidative status and blood pressure in subjects with stage 1 hypertension. The experimental group (n = 13) was supplemented with 200 g of tomato fruit juice enriched with 1 g of ethanolic extract of whole tomato fruit, while the control group (n = 13) was consuming 200 g tomato fruit juice. Before and after the treatment, blood samples were collected, and blood pressure was measured. Markers of oxidative stress and antioxidative defense: paraoxonase (PON1), thiobarbituric acid reactive substances (TBARS), total antioxidant status (TAS), total oxidant status (TOS), pro-oxidant-antioxidant balance (PAB) and C reactive protein (CRP) were determined in serum. Prothrombin time (PT) was measured in the whole blood samples. Parameters of lipid status, as well as susceptibility to copper-induced oxidation of LDL particles in vitro were also determined. There was a significant reduction in total cholesterol and LDL-C only in the control group at the end of the study. No significant differences were observed in the remainder of the assessed parameters along the study. In conclusion, tomato juice may have favorable effects on lipid metabolism, but polyphenol fortification does not constitute additional beneficial cardiovascular effects.

Effects of Probiotic Supplementation on Selected Parameters of Blood Prooxidant-Antioxidant Balance in Elite Athletes: A Double-Blind Randomized Placebo-Controlled Study.

A randomized, double-blind, placebo-controlled study was conducted, in order to evaluate if Lactobacillus helveticus Lafti® L10 (Lallemand Health Solutions, Montreal, Canada) supplementation during three months could influence oxidative markers in the population of elite athletes: triathletes, cyclists and endurance athletes. Twenty-two elite athletes were randomized to either placebo (n = 12) or probiotic (n = 10) groups. The probiotic group received 2x1010 colony forming units of Lafti® L10. Before and after the supplementation serum samples were collected. Markers of oxidative stress and anti-oxidative defense: superoxide dismutase (SOD), paraoxonase (PON), advanced oxidation protein products (AOPP), malondialdehyde (MDA), total antioxidant status, total oxidant status, pro-oxidant-antioxidant balance, oxidative stress index, bilirubin, uric acid and albumin were determined in serum. Parameters of lipid status, as well as susceptibility to copper-induced oxidation of LDL particles in vitro were also determined. There was a significant interaction effect for MDA (p = 0.039), with a decrease in MDA in the probiotic group only (p = 0.049). There was a significant interaction effect for AOPP (p = 0.037), with a significant decrease in the probiotic group (p = 0.045). Interaction effect for SOD was approaching to formal significance (p = 0.108) and the post-hoc test showed a significant decrease in the probiotic group (p = 0.041) only. A significant correlation between AOPP and SOD (p = 0.012, r = -0.40) was found in the probiotic group at the end of the study. PON1 activity was decreased in both the probiotic (p = 0.032) and placebo group (p = 0.035). No significant changes in the remainder of the evaluated parameters were noted. In conclusion, probiotic strain Lafti® L10 exerts certain antioxidant potential, but further research is needed.