Pharmacokinetics and Target Attainment of Ceftobiprole in Asian and Non-Asian Subjects

Ceftobiprole is a broad-spectrum cephalosporin. The objective of this study was to test the hypothesis that the pharmacokinetics (PK) and exposure of ceftobiprole in Asian subjects are similar to those in non-Asian subjects. Three approaches were followed. The first compared the individual PK estimates between the 2 subgroups derived from a population PK model previously built. Next, it was determined whether “Asian subject” was a significant covariate. Finally, a pharmacodynamic analysis was performed by comparing measures of exposure and target attainment. No significant differences were found between PK parameter estimates for Asian and non-Asian subjects, with median values (range) for clearance of 4.82 L/h (2.12–10.47) and 4.97 L/h (0.493–20.6), respectively (P =.736). “Asian subject” was not a significant covariate in the population PK model. There were no significant differences between the measures of exposure. The geometric mean ratio for the fAUC was 1.022 (90%CI, 0.91–1.15), indicating bioequivalence. Taking a target of 60% coverage of the dose interval, more than 90% of the population in both subgroups was adequately exposed. This analysis demonstrated that there are no PK or pharmacodynamic differences between Asian and non-Asian subjects for a ceftobiprole dose of 500 mg every 8 hours as a 2-hour infusion

Experience in implementing harvest strategies in Australia's south-eastern fisheries

The Southern and Eastern Scalefish and Shark Fishery (SESSF) is a complex multi-species fishery, with 34 stock units under quota management, for which a harvest strategy framework was developed in 2005. The framework involves the application of a set of tier-based harvest control rules (HCR) designed to provide a precautionary approach to management. The harvest strategy framework has been applied from 2005 to 2007, resulting in substantial reductions in quotas across the fishery. The experience in implementing the framework, both positive and negative, is described, and general lessons are drawn. Key lessons include the importance of formally testing such strategies using management strategy evaluation, the impact of external management drivers on implementation of the approach, the need to define strategies for setting "bycatch quotas" in multi-species fisheries, and the need for flexibility and pragmatism in the early stages of implementing such an approach

Exposure to ceftobiprole is associated with microbiological eradication and clinical cure in patients with nosocomial pneumonia

Contains fulltext : 138004.pdf (publisher's version ) (Open Access)The percentage of the dosing interval that the non-protein-bound plasma concentration is above the MIC (%fT>MIC) for cephalosporins has been shown to correlate with microbiological outcomes in preclinical studies. However, clinical data are scarce. Using data from a randomized double-blind phase 3 clinical trial, we explored the relationship of ceftobiprole exposure with microbiological and clinical outcomes in patients with nosocomial pneumonia. The individual ceftobiprole exposure was determined for different pharmacokinetic (PK)/pharmacodynamic (PD) indices using individual pharmacokinetic data and a previously published population model. The MICs used in the analysis were the highest MICs for any bacterium cultured at baseline or the end of treatment (EOT). Outcomes were microbiological cure at EOT and clinical cure at test of cure (TOC). Multiple logistic regression (MLR) and classification and regression tree (CART) analyses were applied to determine the relationships among exposure, patient characteristics, and outcomes. MLR indicated that the %fT>MIC of ceftobiprole was the best predictor for both microbiological eradication and clinical cure. CART analysis showed a breakpoint value of 51.1% (n = 159; P = 0.0024) for clinical cure, whereas it was 62.2% (n = 251; P MIC required to result in a favorable clinical outcome is >51% of the dosing interval, which is in line with the values found for microbiological eradication, the comparator ceftazidime, and preclinical models

Some comments regarding the ICSEAF protocol for testing assessment methodologies

Documento de trabajo preparado para el comité de metodología de evaluación de la International Commission for the Southeast Atlantic Fisheries (ICSEAF) - Commission Internatinale des Pêches de l'Atlantique Sud-Est (CIPASE) - Comisión Internacional de Pesquerías del Atlántico Sud-Oriental (CIPASO), que no llegó a presentarse en la segunda reunión de 1990 debido a su disolución.-- 17 pages, 1 figure, 1 table, 1 appendixPeer Reviewe

Assessing the management-related benefits of fixed-station fishery-independent surveys in Australia’s Southern Shark Fishery

Monte Carlo simulation is used to assess the benefits of different levels of survey intensity for a programme of fixed-station surveys using gill-nets, in terms of the ability to satisfy the management objectives for gummy shark, Mustelus antarcticus, in Bass Strait, Australia. The simulations consider the entire management process: Data collection, data analysis, stock assessment, and setting of total allowable catches (TACs). The use in assessments of survey results rather than future commercial catch rates leads to a marked improvement in the ability to satisfy the legislative management objective for Australian fisheries of Ecological Sustainable Development, especially if future catch rates are not related linearly to abundance or if catchability is density-dependent. The benefits of more than six stations per survey site appear limited, however, because of the possible impact of variability in survey results due to factors unrelated to sampling

Model uncertainty in the ecosystem approach to fisheries

Fisheries scientists habitually consider uncertainty in parameter values, but often neglect uncertainty about model structure. The importance of this latter source of uncertainty is likely to increase with the greater emphasis on ecosystem models in the move to an ecosystem approach to fisheries (EAF). It is therefore necessary to increase awareness about pragmatic approaches with which fisheries modellers and managers can account for model uncertainty and so we review current ways of dealing with model uncertainty in fisheries and other disciplines. These all involve considering a set of alternative models representing different structural assumptions, but differ in how those models are used. The models can be used to identify bounds on possible outcomes, find management actions that will perform adequately irrespective of the true model, find management actions that best achieve one or more objectives given weights assigned to each model, or formalise hypotheses for evaluation through experimentation. Data availability is likely to limit the use of approaches that involve weighting alternative models in an ecosystem setting, and the cost of experimentation is likely to limit its use. Practical implementation of the EAF should therefore be based on management approaches that acknowledge the uncertainty inherent in model predictions and are robust to it. Model results must be presented in a way that represents the risks and trade-offs associated with alternative actions and the degree of uncertainty in predictions. This presentation should not disguise the fact that, in many cases, estimates of model uncertainty may be based on subjective criteria. The problem of model uncertainty is far from unique to fisheries, and coordination among fisheries modellers and modellers from other communities will therefore be useful

Stock assessment of school shark, Galeorhinus galeus, based on a spatially explicit population dynamics model

The school shark (Galeorhinus galeus) resource off southern Australia is assessed by use of an assessment approach that takes account of the spatial structure of the population. The population dynamics model underlying the assessment considers the spatial as well as the age-specific characteristics of school shark. It allows for a series of fisheries (each based on a different gear type), explicitly models the pupping/recruitment process, and allows for multiple stocks. The values for the parameters of this model are determined by fitting it to catch-rate data and information from tagging studies. The point estimates of the pup production at the start of 1997 range from 12% to 18% of the pre-exploitation equilibrium size, depending on the specifications of the assessment. Allowing for spatial structure and incorporating tag release–recapture data lead to reduced uncertainty compared with earlier assessments. The status of the resource, as reflected by the ratio of present to virgin pup production and total (1+) biomass, is sensitive to the assumed level of movement between the stocks in New Zealand and those in Australia, with lower values corresponding to higher levels of movement