Development of Standardized Antimicrobial Susceptibility Testing Methods and Aeromonas salmonicida Epidemiologic Cutoff Values for Antimicrobial Agents Used in Aquaculture

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dc.contributor.advisorKane, Andrew Sen_US
dc.contributor.authorMiller, Ron Ashleyen_US
dc.contributor.departmentMarine-Estuarine-Environmental Sciencesen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2007-09-28T14:59:18Z
dc.date.available2007-09-28T14:59:18Z
dc.date.issued2007-07-27en_US
dc.description.abstractPharmacokinetics describes the time course of drug absorption, distribution, metabolism and excretion. Pharmacodynamics is the relationship between unbound drug concentration over time and the resulting antimicrobial effect. Pharmacokinetic/ pharmacodynamic (PK/PD) indices quantify the relationship between pharmacokinetic parameters (i.e., area under the concentration-time curve, AUC) and microbiological parameters (i.e., minimal inhibitory concentrations, MICs), and are used to establish interpretive criteria or clinical breakpoints. The three primary PK/PD indices used are the AUC over 24 h at steady-state/MIC (AUCss/MIC), the peak concentration/MIC (Cmax/MIC), and the percentage of time over 24 hours that the drug concentration exceeds the MIC at steady-state pharmacokinetic conditions (T>MIC). These indices can be used to determine both appropriate dosage regimens and index magnitudes required for efficacy and reduced antimicrobial resistance emergence. The goal of this work was to determine the relevant PK/PD index target (AUCss/MIC) for oxytetracycline (OTC) against Aeromonas salmonicida, causative agent of furunculosis in salmonids. To achieve this goal we first established a standardized MIC testing method for aquatic bacterial pathogens, then used this method to determine the in vitro susceptibility cutoff concentration (epidemiologic cutoff value) for OTC (and three other antimicrobial agents) against 217 A. salmonicida isolates. We conducted additional in vivo studies using rainbow trout to monitor achievable serum OTC concentrations in both healthy and A. salmonicida-challenged fish. We confirmed OTC to be highly efficacious against a susceptible A. salmonicida strain in vivo, and through pharmacokinetics studies, calculated the OTC AUCss in healthy and challenged fish to be 27.2 and 20.1 μg∙h/mL, respectively. The PK/PD index target reported in a neutropenic mouse model as the most applicable to the tetracyclines is an AUCss/MIC of ≥5. Either of the AUCss values divided by the current epidemiologic cutoff value for A. salmonicida isolates (1 μg/mL) yields a product greater than this AUCss/MIC target of ≥5. This work demonstrates PK/PD indices commonly used in studies in mammals to predict therapeutic efficacy can be applied in studies in fish.en_US
dc.format.extent2233106 bytes
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/1903/7256
dc.language.isoen_US
dc.subject.pqcontrolledAgriculture, Fisheries and Aquacultureen_US
dc.subject.pqcontrolledBiology, Veterinary Scienceen_US
dc.subject.pqcontrolledAgriculture, Fisheries and Aquacultureen_US
dc.subject.pquncontrolledAeromonas salmonicidaen_US
dc.subject.pquncontrolledpharmacokineticsen_US
dc.subject.pquncontrolledantimicrobial susceptibility testingen_US
dc.subject.pquncontrolledfishen_US
dc.subject.pquncontrolledaquacultureen_US
dc.subject.pquncontrolledMICen_US
dc.titleDevelopment of Standardized Antimicrobial Susceptibility Testing Methods and Aeromonas salmonicida Epidemiologic Cutoff Values for Antimicrobial Agents Used in Aquacultureen_US
dc.typeDissertationen_US

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