Factors influencing caspofungin plasma concentrations in patients of a surgical intensive care unit.

BACKGROUND: Co-morbidity, medical and surgical interventions often cause alterations to drug plasma concentrations and pharmacokinetic parameters in critically ill patients. In the present study, we investigated parameters influencing plasma caspofungin concentrations in patients of a surgical intensive care unit (SICU). METHODS: In a monocentre open study, caspofungin trough concentrations (C(24)) were determined for a group of SICU patients. A linear-mixed model was then used to assess factors influencing caspofungin plasma concentrations. RESULTS: A total of 40 SICU patients were enrolled. Age and body weight ranged from 22 to 76 years and 47 to 108 kg, respectively. All participants received a caspofungin loading dose of 70 mg and a maintenance dose of 50 mg/day. The median duration of therapy was 10 days. Caspofungin C(24) in SICU patients varied more than those determined for healthy subjects reported in previous studies (0.52-4.08 microg/mL versus 1.12-1.78 microg/mL). According to our model, caspofungin C(24) were predicted to be significantly higher in patients with body weight <75 kg (P=0.019) and patients with albumin concentration >23.6 g/L (P=0.030). CONCLUSIONS: Our results show that body weight and albumin concentration influence caspofungin C(24) in SICU patients and should therefore be considered prognostic factors.

A holistic passive integrative sampling approach for assessing the presence and potential impacts of waterborne environmental contaminants.

As an integral part of our continuing research in environmental quality assessment approaches, we have developed a variety of passive integrative sampling devices widely applicable for use in defining the presence and potential impacts of a broad array of contaminants. The semipermeable membrane device has gained widespread use for sampling hydrophobic chemicals from water and air, the polar organic chemical integrative sampler is applicable for sequestering waterborne hydrophilic organic chemicals, the stabilized liquid membrane device is used to integratively sample waterborne ionic metals, and the passive integrative mercury sampler is applicable for sampling vapor phase or dissolved neutral mercury species. This suite of integrative samplers forms the basis for a new passive sampling approach for assessing the presence and potential toxicological significance of a broad spectrum of environmental contaminants. In a proof-of-concept study, three of our four passive integrative samplers were used to assess the presence of a wide variety of contaminants in the waters of a constructed wetland, and to determine the effectiveness of the constructed wetland in removing contaminants. The wetland is used for final polishing of secondary-treatment municipal wastewater and the effluent is used as a source of water for a state wildlife area. Numerous contaminants, including organochlorine pesticides, polycyclic aromatic hydrocarbons, organophosphate pesticides, and pharmaceutical chemicals (e.g., ibuprofen, oxindole, etc.) were detected in the wastewater. Herein we summarize the results of the analysis of the field-deployed samplers and demonstrate the utility of this holistic approach.

Estrogenicity of solid phase-extracted water samples from two municipal sewage treatment plant effluents and river Rhine water using the yeast estrogen screen.

In the present study, the yeast estrogen screen (YES) was used to estimate the estrogenic potential of solid phase-extracted water samples from the effluents of two municipal sewage treatment plants (STPs 1 + 2) and from four lanes (left to right) of the river Rhine at Worms, Germany, i.e. downstream the STPs. Estrogenic activities of extracted water samples were expressed as 17beta-estradiol equivalents (E(2)-EQs). Estrogenic activity was detected in the effluents of both STPs with values of 0.242 +/- 0.038 nM (65.96 +/- 10.4 ng/l) and 0.125 +/- 0.026 nM E(2)-EQs (34.1 +/- 7.18 ng/l) at STP 1 and 2, respectively. In river Rhine water, estrogenic activity was lower, however, displaying significant differences between the left and right bank of the river (0.044 +/- 0.003 nM E(2)-EQs [11.97 +/- 0.7 ng/l] for lanes 1-3; 0.071 +/- 0.01 nM E(2)-EQs [19.42 +/- 2.8 ng/l] for lane 4). Chemical analysis of corresponding water samples resulted in a potential estrogenic response in the YES, expressed as E(2)-EQs for the known estrogens and phytoestrogens in the STP effluents with values up to 0.0662 nM E(2)-EQs (18.04 ng/l). In Rhine water from lane 4, however, total estrogenic activity of steroidal estrogens was equal to 0.014 nM E(2)-EQs (3.8 ng/l). Furthermore, total concentrations of flavonoids, fecal- and phytosteroids and resorcyclic lactones were about 1.2 microg/l at STP 1, 0.62 microg/l at STP 2 and 0.25 microg/l at the river Rhine, lane 4. Results indicate that estrogenic activity can clearly be measured in SPT effluents as well as in river Rhine water using the YES in combination with chemical analysis. Results from the bioassay, however, indicated a higher estrogenic potential (expressed as E(2)-EQs) than that obtained by chemical analysis.