Biology Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2749
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Item Development of Standardized Antimicrobial Susceptibility Testing Methods and Aeromonas salmonicida Epidemiologic Cutoff Values for Antimicrobial Agents Used in Aquaculture(2007-07-27) Miller, Ron Ashley; Kane, Andrew S; Marine-Estuarine-Environmental Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Pharmacokinetics 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.Item Hepatic Phase I and II Biotransformation Kinetics in Fishes: A Comparative Study(2006-12-04) Gonzalez, Jaime Fernando; Kane, Andrew S; Marine-Estuarine-Environmental Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Eight finfish species were selected to test the similarities and dissimilarities on their phase I and II biotransformation capabilities using microsomal and cytosolic fractions of the liver. This research had three main objectives: 1) a comparison among the kinetics of the 8 species using model substrates, 2) farm-raised and laboratory-acclimated specimens of channel catfish, rainbow trout and tilapia were compared to determine similarities and differences in the biotransformation reactions, and 3) the same latter three species were tested to compare in vitro hepatic metabolism of albendazole, a drug that undergoes metabolic biotransformation mainly through hepatic phase I reactions. The comparison among the 8 finfish species showed that some of them had higher biotransformation capabilities than others. For most of the seven phase I- II reactions that were tested; rainbow trout, tilapia, channel catfish and Atlantic salmon had higher enzymatic efficiencies than those showed by of striped bass, hybrid striped bass and bluegill. Largemouth bass shared some enzymatic capabilities with one group or the other. The comparison between lab-acclimated and farm-raised specimens of tilapia, channel catfish and rainbow trout did not show biologically significant differences among the two groups of fish for the 3 species. All the values found for the kinetics of the reactions were within the ranges of the constitutive expression that has been reported for them and far below those found in other works when inducers (e.g. pollutants) of enzymatic reactions have been used. The phase I-mediated hepatic sulfoxidation of albendazole in tilapia, channel catfish and rainbow trout showed significant differences in Vmax and Km values among the three species. However, the catalytic efficacies of the reaction (Vmax/Km) in the 3 species transforming the parent compound were similar. In addition, albendazole induced EROD activity (2.6 fold) in in vivo dosed channel catfish. The results found in the present study showed that the catalytic efficiency of hepatic phase I-II enzymatic reactions varied among finfish species. Some of them may be categorized as "more efficient metabolizers" than others. This may have important implications in drug metabolism and residue depletion patterns.Item GROWTH OF EASTERN OYSTER, CRASSOSTREA VIRGINICA, IN CHESAPEAKE BAY(2004-05-14) Coakley, Jessica; Miller, Thomas J; Marine-Estuarine-Environmental SciencesI applied modern techniques of modal analysis to track size modes in Eastern oyster, Crassostrea virginica, populations longitudinally through time, from which I inferred age-classes to establish size-at-age relationships for individual oyster bars and across Maryland's Chesapeake Bay. Average shell lengths of putative age-0 through age-5 oysters range from 22.93 (6.67, n=194) mm to 84.46 (8.27, n=4) mm. Growth rates declined with age-class from a mean of 28.97mm/yr to 0.85mm/yr, and the maximum and minimum individual growth rates were 0.78 and 53.0 mm/yr, respectively. I estimated von Bertalanffy growth parameters across all sites as L90.85mm, k=0.55, and to=-0.51. On average, I estimated oysters take 3 years to reach a marketable size within Chesapeake Bay. As an alternative to modal length frequency analysis, annuli in chondrophore sections of known-age oysters in Chesapeake were examined. It was determined that annuli formation was unrelated to chronological age.