Penetration of daptomycin into bone and synovial fluid in joint replacement.

Daptomycin exhibits clinical activity in the treatment of infections with Gram-positive organisms, including infections due to methicillin-resistant Staphylococcus aureus. However, little is known about its penetration into bone and synovial fluid. The aim of our study was to assess the penetration of daptomycin into bone and synovial fluid after a single intravenous administration. This study was conducted in 16 patients who underwent knee or hip replacement and received a single intravenous dose of 8 mg of daptomycin per kg of body weight prior to surgery. Plasma daptomycin concentrations were measured 1 h after the end of daptomycin infusion and when bone fragments were removed. Daptomycin concentrations were also measured on bone fragments and synovial fluid collected at the same time during surgery. All samples were analyzed with a diode array-high-performance liquid chromatography (HPLC) method. After a single-dose intravenous infusion, bone daptomycin concentrations were above the MIC of daptomycin for Staphylococcus aureus in all subjects, and the median bone penetration percentage was 9.0% (interquartile range [IQR], 4.4 to 11.4). These results support the use of daptomycin in the treatment of Staphylococcus aureus bone and joint infections.

Impact of everolimus blood concentration on its anti-cancer activity in patients with metastatic renal cell carcinoma.

PURPOSE: Everolimus has demonstrated its efficacy in metastatic renal cell carcinoma (mRCC). Preliminary studies have shown high variability of everolimus blood concentrations (EBC). In other settings, its activity was correlated with EBC. We therefore decided to monitor EBC in patients treated with mRCC to assess its influence on oncologic outcomes. PATIENTS AND METHODS: Our study analyzed first 3 months' trough EBC levels in 42 patients treated in 4 French oncologic centers between March 2010 and August 2013. Patients presented a histologically confirmed diagnosis of mRCC and have failed prior anti-angiogenic (AA) therapies. RESULTS: Median follow-up was 25.9 months. A total of 113 EBC were analyzed. The median trough concentration was 14.1 µg/L (range 2.6-91.5). Fourteen patients (67 %) versus 8 (38 %) patients with median EBC above or below 14.1 µg/L were free from progression at 6 months (p = 0.06). Median progression-free survival was 13.3 versus 3.9 months (HR 0.66 95 % CI 0.33-1.31; p = 0.23), and the median overall survival was 26.2 versus 9.9 months (HR 0.62 95 % CI 0.28-1.37; p = 0.24), for patients above or below the median value of trough concentrations, respectively. CONCLUSION: Impact of drug exposure for AA tyrosine kinase inhibitors activity has been demonstrated in mRCC setting. Interpatients EBC variability was confirmed in the present study, and the results suggest a relationship between initial EBC within the first 3 months and the drug activity. It underlines the need to prospectively include EBC monitoring in future clinical trials to determine the need of its implementation in routine use.

Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study.

BACKGROUND: Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis. METHODS: Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with (n=26) or without (n=29) epinephrine were analysed using NONMEM. RESULTS: Epinephrine halves clearance between peritoneum and serum (IPCL) and increases the Pt central volume of distribution, IP exposure and penetration in tissue. IPCL has a better predictive value than any other parameter with respect to renal toxicity. CONCLUSION: This confirms that IPCL could be useful in assessing renal toxicity. As IPCL is also linked to tissue penetration and IP exposure, it may be proposed as biomarker. In addition to a Bayesian estimation, we propose a single-sample calculation-way to assess it. Prospective studies are needed to validate IPCL as a biomarker in this context.

Impact of filter mud applications on the germination of sugarcane and small-seeded plants and on soil and sugarcane nitrogen contents.

The impact of filter mud (FM) on the germination of sugarcane (Saccharum spp.), guar (Cyamopsis tetragonoloba), maize (Zea mays), groundnut (Arachis hypogaea) and sesame (Sesamum indicum), and the nitrogen content of soil and sugarcane were investigated. Experiments were set up in 2004 at the Kenana Sugarcane Estate, Sudan. For this study, 1:0,3:1,1:1,1:3 and 0:1 FM/soil (w/w) mixtures were used. The results showed that FM had no adverse impact on germination. Soil organic carbon and total nitrogen after 3 months increased with an increase in the FM content of the mixture. The impact of 100 t of dry FM was compared to a control without FM, and to inorganic nitrogen fertilizer applications of 0, 55, 110, 165 and 220 Kg N/ha. Cane yield, number of stalks, soil and leaf analysis results were determined after 6 months. FM treated soil gave a higher cane yield and stalk number. Leaf analysis showed no significant difference in nutrient content.

Influence of bulking agents and microbial activator on thermophilic aerobic transformation of sewage sludge.

Bangkok, while improving the wastewater treatment in order to alleviate the river pollution, faces important amounts of sewage sludge. The sewage sludge contains organic matter, nitrogen and phosphorus available for plant growth. However, it may contain pathogenic microorganisms. To be used for agricultural purposes, these pathogens should be destroyed, which can be achieved with the thermophilic phase of composting. As the sewage sludge is dense and unable to compost alone (low C/N ratio), it should be mixed with an organic by-product. Two by-products available in large quantities in Thailand (wood chips and rice husk) have been tested for mixture with sewage sludge. As these products are not easy to decompose (presence of silica in rice husk and lignin/tannins in wood chips), the addition of a microbial activator for composting has been tested in controlled conditions (small quantities of organic mixtures, 55 degrees C, moisture maintained at 60-70% of water holding capacity). The monitoring of the decomposition has been made by measuring the carbon dioxide respiration, pH, organic matter and nitrogen contents and the evolution of enzymatic activities. When mixed with sewage sludge, wood chips and rice husk do not show significant differences concerning decomposition after 63 days. The use of an activator within the experimental conditions does not improve the decomposition of organic matter contained in the mixture of sewage sludge and rice husk or wood chips.

[Diagnostic value of a new serum marker of human digestive cancer: the carbohydrate antigen 19.9; comparison with the carcinoembryonic antigen]. / Valeur diagnostique d'un nouveau marqueur sérique des cancers digestifs humains: l'antigène carbohydrate 19.9 (CA 19.9); comparaison avec l'antigène carcino-embryonnaire.

In order to evaluate its diagnostic value for digestive cancers, the carbohydrate antigen 19.9 (CA 19.9) was quantitated by radioimmunoassay in the serum of 102 patients suffering from malignant or non-malignant diseases of the digestive or pulmonary tract and of 20 healthy subjects. The carcinoembryonic antigen (CEA) was quantitated by enzyme-immunoassay in the same sera. No correlation was found between the CA 19.9 and the CEA levels. The sensitivity of the CA 19.9 test for the detection of digestive cancers (0.51) was not significantly higher than neither that of the CEA assay (0.46), nor that of the combined tests (0.59). Numerous false positive results were encountered in the CA 19.9 assay in pulmonary diseases and in non-cancerous liver diseases, especially cirrhosis. Its specificity (0.84) did not prove to be superior to that of CEA (0.90). Thus, in our experience, the clinical interest of serum CA 19.9 determination for the diagnosis of digestive cancers seems doubtful.