Class of 2011 Abstract / OBJECTIVES: Five methods for estimating vancomycin pharmacokinetic parameters were studied to determine the accuracy of each method in predicting vancomycin concentration. METHODS Patient vancomycin pharmacokinetic data from a prior study were retrospectively reviewed and used in five methods to calculate vancomycin clearance and volume of distribution in order to determine the accuracy in prediction of the measured value. RESULTS: The coefficients of determination ranged from 0.167 to 0.224, bias ranged from -5.18 to 2.13, and precision ranged from 5.98 to 7.64. The Buelga method had the highest percentage of predictions within 2.5 and 5 mg/L of the measured trough at 42% and 65% respectively, while the Thomson method had the highest percentage of predictions within 50% of the measured trough at 52%. The highest percentage of predictions within 25% of the measured trough were found with both the Thomson and Yasuhara method at 29%. CONCLUSION: There was wide variation in the prediction of vancomycin trough concentrations from the five methods for estimating vancomycin pharmacokinetic parameters. None of the methods provided adequate reliability to recommend discontinuation of therapeutic drug monitoring for vancomycin.

Enterococci bacteria that cannot be treated eectively with the antibiotic vancomycin are termed Vancomycin-Resistant Enterococci (VRE). In this thesis, we develop a mathematical framework for determining optimal strategies for prevention and treatment of VRE in an Intensive Care Unit (ICU). A system of ve ordinary dierential equations describes the movement of ICU patients in and out of dierent states related to VRE infection. Two control variables representing the prevention and treatment of VRE are incorporated into the system. An optimal control problem is formulated to minimize the VRE-related deaths and costs associated with controls over a nite time period. Pontryagin's Minimum Principle is used to characterize optimal controls by deriving a Hamiltonian expression and dierential equations for ve adjoint variables. Numerical solutions to the optimal control problem illustrate how hospital policy makers can use our mathematical framework to investigate optimal cost-eective prevention and treatment schedules during a VRE outbreak. / McAnulty College and Graduate School of Liberal Arts; / Computational Mathematics / MS; / Thesis;

Thesis advisor: Steven D. Bruner / Complex and unique enzymology is often behind the biosynthesis of natural products. This thesis is focused on how non-proteinogenic amino acids are biosynthesized and then incorporated into natural products. Chapters two, three and four deal with a unique dioxygenase found in vancomycin biosynthesis. Chapter five elaborates on the biochemical characterization along with efforts toward structural characterization of a terminal non-ribosomal peptide synthetase module. The vancomycin biosynthetic enzyme DpgC belongs to a small class of oxygenation enzymes that are not dependent on an accessory cofactor or metal ion. The detailed mechanism of cofactor-independent oxygenases has not been established. We have solved the first structure of an enzyme of this oxygenase class complexed with a bound substrate mimic. The use of a designed, synthetic substrate analog allows unique insights into the chemistry of oxygen activation. The structure confirms the absence of cofactors, and electron density consistent with molecular oxygen is present adjacent to the site of oxidation on the substrate. Molecular oxygen is bound in a small hydrophobic pocket and the substrate provides the reducing power to activate oxygen for downstream chemical steps. Our results resolve the unique and complex chemistry of DpgC, a key enzyme in the biosynthetic pathway of an important class of antibiotics. Mechanistic parallels exist between DpgC and cofactor-dependent flavoenzymes, providing information regarding the general mechanism of enzymatic oxygen activation. / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis (M. Med. Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 64-73).

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis (M. Med. Sc.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves 31-37).

Thesis (M.Med.Sc.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves 31-37). Also available in print.

Thesis (M.Med.Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 64-73). Also available in print.

Thesis (M.S.)--Ohio State University. / Bibliography: leaves 57-63. Available online via OhioLINK's ETD Center.

Orientador: Matthieu Tubino / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-13T14:10:39Z (GMT). No. of bitstreams: 1 RodriguesJunior_Alvino_M.pdf: 694987 bytes, checksum: 1b71ae2953ae2ae4410308e036a7f084 (MD5) Previous issue date: 2008 / Resumo: Este trabalho teve por objetivo o desenvolvimento de um método analítico quantitativo de para análise de vancomicina (em sua forma denominada vancomicina base - VCM, e na forma de cloridrato de vancomicina - HVCM), com utilização de espectrofotometria na região do visível. O método tem como princípio a reação da vancomicina com íons cobre(II), resultando na formação de um complexo de coloração lilás, que apresenta absorção máxima em 555 nm. Realizaram-se estudos para a otimização da reação entre a vancomicina e o íon cobre(II). Dentre estes fatores, destacam-se: a escolha do sal de cobre(II) utilizado na reação com vancomicina; a utilização de etanol, no preparo das soluções e como componente do meio reacional; pH do meio reacional; proporção molar entre vancomicina e íon cobre(II). A otimização destes parâmetros resultou em um método com faixa de trabalho de 1,0 × 10 mol L a 1,0 × 10 mol L, com coeficiente de correlação de 0,9997 e limite de detecção (LOD) e limite de quantificação (LOQ) de 4,0 × 10 mol L e 1,0 × 10 mol L, respectivamente. O método proposto também foi estudado em relação à recuperação de vancomicina frente a excipientes comumente utilizados na indústria farmacêutica. Os resultados obtidos foram comparados com método de referência cromatográfico, onde foi observado que o método proposto apresentou maior repepetibilidade para as amostras de HVCM e maior recuperação para as amostras de VCM. O procedimento para a realização de análises pelo método proposto é de fácil execução e de baixo custo / Abstract: The aim of this work was to develop a quantitative spectrophotometric analytical method, in the visible region of the spectrum, for the determination of vancomycin (in the form known as base ¿ VCM, and in the form of chloridrate, HVCM). The developed method uses the reaction between vancomycin and ions copper(II) that forms a lilac complex which spectrum shown a maximum at 555 nm. Studies were done in order to optimize the method. Among them can be cited: selection of the copper(II) salt to be used in the reaction with vancomycin; use of ethanol as component of the reaction for the preparation of the solution and as component of the reaction medium; pH of the reaction medium; molar proportion between vancomycin and copper(II) ions. The parameters optimization resulted in a method with a linear range from 1,0 × 10 mol L to 1,0 × 10 mol L, with correlation coefficient value of 0,9997, limit of detection (LOD) and limit of quantification (LOQ) values of 4,0 × 10 mol L and 1,0 × 10 mol L, respectively. The proposed medium was also studied with respect to the vancomycin recovering when mixed with excipients commonly used in the pharmaceutical industry. The obtained results were compared with those of the reference chromatographic method (HPLC), where it was observed the proposed method showed a better reprodutibility for HVCM samples and higher recoveries for VCM samples. The analytical procedure that is proposed in this work is simple to be performed and the cost is very low / Mestrado / Quimica Analitica / Mestre em Química