Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available in print.

Thesis (Ph. D.)--School of Biology, Georgia Institute of Technology, 2005. Directed by Paul Edmonds. / Paul Edmonds, Committee Chair ; Steve Harvey, Committee Member ; Igor Zhulin, Committee Member ; Yury Chernoff, Committee Member ; Mostafa El-Sayed, Committee Member. Includes bibliographical references.

Diss. Naturwissenschaften Zürich, 1990. / Rückentitel: Resistenz von P. aeruginosa gegen Betalaktam-Antibiotika. Name auch: U. Vurma-Rapp.

京都大学 / 新制・論文博士 / 博士(工学) / 乙第13581号 / 論工博第4212号 / 新制||工||1990(附属図書館) / (主査)教授 松原 誠二郎, 教授 中尾 佳亮, 教授 浦山 健治 / 学位規則第4条第2項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

Context: Daptomycin is the only antibiotic available with in vitro bactericidal activity against vancomycin-resistant enterococci (VRE). Its increased use has resulted in cases of decreased daptomycin efficacy. Recent in vitro studies have shown effective use of beta (beta)-lactam and daptomycin antibiotics, as a combination therapy, in the treatment of VRE. We describe a case of effective treatment in a patient with VRE infection using dual ampicillin and daptomycin therapy that shows bench-to-bedside application of the abovementioned finding. Case Report: A 76-year-old gentleman with a history of bilateral arthroplasty was admitted with a swollen left knee. Blood cultures were positive for Enterococcus faecium. Left knee joint aspiration showed leukocytosis and alpha defensins. Extensive imaging did not show any other source of infection. Culture sensitivity results showed multidrug-resistant enterococci sensitive to daptomycin. The patient was started on intravenous (IV) daptomycin. His left knee prosthesis was explanted and a spacer was placed. The patient continued to be bacteremic for 10 days after removing the knee prosthesis. The patient was trialed on combination IV ampicillin and daptomycin. His blood culture turned negative 2 days later. The patient was discharged home to continue 6 weeks of IV ampicillin and daptomycin. Conclusion: The exact mechanism of the daptomycin/ampicillin synergy effect is unclear. Current hypothesis suggests that ampicillin causes a reduction in the net positive charge of the bacterial surface, possibly by releasing lipoteichoic acid (LTA) from the cell wall. This process increases the ability of the cationic daptomycin/calcium complex to bind to the cell wall more effectively. Our case shows the clinical application of the same. A prospective randomized control trial to explore the effectiveness of dual antibiotic therapy in vivo is needed. If proven, daptomycin/-lactam can become a standard of care to treat VRE and decrease daptomycin nonsusceptibility.

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

Dentre os bacilos Gram-negativos não fermentadores (BGNNF), Acinetobacter baumannii, complexo Burkholderia cepacia, Pseudomonas aeruginosa e Stenotrophomonas maltophilia se destacam devido à ampla capacidade de adaptação, as quais podem habitar uma grande variedade de ambientes e adquirir resistência a uma grande variedade de antimicrobianos. A resistência aos ?-lactâmicos ocorre principalmente pela produção de enzimas do tipo ?-lactamases, as quais são capazes de clivar o anel ?-lactâmico. O objetivo do presente estudo foi isolar bactérias pertencentes a esses gêneros, determinar o perfil de resistência aos antimicrobianos através dos métodos de disco difusão e da concentração inibitória mínima (CIM) e investigar a presença de genes codificadores de ?-lactamases. Foram isolados 60 BGNNF, sendo 24 pertencentes ao complexo B. cepacia, 13 P. aeruginosa, 13 S. maltophilia e 10 A. baumannii obtidos de diferentes amostras de solo provenientes de diferentes estados e cidades das cinco regiões do Brasil. Dentre os isolados, 50 (83,3%) foram não suscetíveis a pelo menos um ?-lactâmico e altas CIMs para as cefalosporinas de amplo espectro foram detectadas. Diferentes genes codificadores ?-lactamases de importância clínica foram pesquisados, e um total de 70 foram detectados, como blaSHV, blaGES, blaOXA-1-like, blaPER, blaVEB, blaCTX-M-Gp1, blaCTX-M-Gp9, blaKPC, blaVIM e blaNDM, sendo que, a maior prevalência foi do blaSHV (46%). Este é o primeiro relato no mundo de uma bactéria isolada do solo com o gene blaKPC e o primeiro relato no Brasil e o segundo no mundo de uma bactéria isolada do solo portadora do gene blaNDM-1. O grande número de genes codificadores de ?-lactamases encontrados indica uma grande disseminação destas enzimas em bactérias isoladas do solo. / Among the nonfermenting Gram-negative bacilli (NFGNB), Acinetobacter baumannii, Burkholderia cepacia complex, Pseudomonas aeruginosa and Stenotrophomonas maltophilia stand out due to the large adaptation capacity, which can inhabit a wide variety of environments and acquire resistance to a wide variety of antibiotics. Resistance to ?-lactam antibiotics occurs mainly by the production of ?-lactamase, which are capable of cleaving the ?-lactam ring. The aim of the present study was to isolate bacteria belonging to these genera, to determine the antimicrobial resistance profile through disc diffusion and minimum inhibitory concentration (MIC) methods and to investigate the presence of ?-lactamase encoding genes. Sixty NFGNB were obtained, being 24 belonging to the B. cepacia complex, 13 P. aeruginosa, 13 S. maltophilia and 10 A. baumannii from different soil samples from different states and cities of the five Brazilian regions. Among the isolates, 50 (83.3%) were not susceptible to at least one ?-lactam antibiotics and high MICs for the extended-spectrum cephalosporins were detected. Different ?-lactamase encoding genes of clinical importance were investigated, and 70 were detected, such as blaSHV, blaGES, blaOXA-1-like, blaPER, blaVEB, blaCTX-M-Gp1, blaCTX-M-Gp9, blaKPC, blaVIM and blaNDM, with the highest prevalence being blaSHV (46%). This is the first report in the world of blaKPC gene in bacteria isolated from soil and the first report in Brazil and the second in the world of blaNDM-1 gene in bacterium isolated from soil. A large number of ?-lactamase encoding genes found indicates a large spread of these enzymes in bacteria isolated from soil.

No description available.

Graduation date: 1994

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