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In the right column the effect on the resistant bacterial populations is shown.
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Teicoplanin is a glycopeptide with a similar spectrum of antibacterial activity to vancomycin.
Three mice were used per dose timepoint.
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We considered both the antibacterial effect of teicoplanin and the emergence of resistance to teicoplanin as primary study endpoints.
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Download 9reat stand by me em karaokePharmacodynamics of teicoplanin against MRSA.
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Download 9reat stand by me em karaokeMonte Carlo simulations were performed with Pmetrics.
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Pharmacodynamics and Therapeutics, Institute of Translational Medicine, University of Liverpool, Liverpool, UK2Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
In vitro susceptibility and mutational frequency.
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Download 9reat stand by me em karaokeFor the adult simulations we used the population PK estimates and covariance matrix from a previously developed population PK model in adults.
Download 9reat stand by me em karaokeEach experiment comprised a control arm and three cohorts of mice receiving teicoplanin.
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In vitro PK studies.
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Download 9reat stand by me em karaokeFor the paediatric simulations, we used the population PK estimates and covariance matrix from a previously developed PK model in children.
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Download 9reat stand by me em karaokeMonte Carlo simulations and probability of target attainment (PTA) analysis.
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MIC target for efficacy and suppression of resistance.
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In vitro PK and PD studies.
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The strain was oxacillin resistant by Etest (Oxoid).
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The mean value of the bacterial burden from the left and right thighs from each mouse was determined.
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We finally bridged the experimental results to patients to reflect on the adequacy of current EUCAST in vitro susceptibility breakpoints.
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PK profile was simulated in the HFIM.
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Monte Carlo simulations from previously developed population PK models in adults and children were conducted to explore the probability of target attainment (PTA) for teicoplanin dosage regimens against the current EUCAST WT susceptibility range.
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Download 9reat stand by me em karaokeThese updated targets are based on small retrospective studies in adults.
These simulated patients were used to examine the outcomes of candidate regimens of teicoplanin.
Pharmacodynamics and Therapeutics, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
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PK and PD studies in a murine thigh infection model.
PD index was then further explored with the in vivo mouse data.
Drug exposure targets that are associated with a high probability of a successful clinical outcome are relatively poorly defined.
The coefficient of determination and visual examination of the fit were used to discriminate the various PD indices.
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Sampling occurred during the first dose interval and at day 6 of therapy.
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Total and resistant subpopulations were quantified.
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Download 9reat stand by me em karaokeCmin at steady state (between days 3 and 4 of treatment) was performed for each dosage regimen for both adults and children.
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Fractional target attainment was calculated for the various regimens.
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PD of teicoplanin against MRSA.
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The MIC for the strain was determined using the EUCAST broth microdilution methodology on three separate occasions.
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Download 9reat stand by me em karaokeThe mean and SD for a group of three mice was then calculated.
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