Activity of antimicrobial peptides, antibiotic combinations and antibiofilm agents against Mycobacterium avium-intracellulare complex and Mycobacteroides abscessus clinical isolates causing nontuberculous mycobacterial lung-disease
[eng] The high-level of antibiotic resistance, the ability to form biofilm as well as the emergence of nontuberculous mycobacteria-lung disease (NTM-LD) by Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus has led to the need for effective treatments against NTM-LD. Curren...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/203567 |
| Acceso en línea: | https://hdl.handle.net/2445/203567 http://hdl.handle.net/10803/689298 |
| Access Level: | acceso abierto |
| Palabra clave: | Malalties del pulmó Resistència als medicaments Biofilms Pulmonary diseases Drug resistance |
| Sumario: | [eng] The high-level of antibiotic resistance, the ability to form biofilm as well as the emergence of nontuberculous mycobacteria-lung disease (NTM-LD) by Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus has led to the need for effective treatments against NTM-LD. Currently available treatments are lengthy, consist on the administration of at least two to three antibiotics, have numerous side effects and show poor treatment outcomes. Further knowledge of MAC and M. abscessus response to different antibiotics is key in finding novel treatment options which result in improved patient management, less side effects and better treatment outcomes. IV. Natural and acquired antibiotic resistance in MAC and M. abscessus is of great concern. Thus, a good characterization of the antibiotic susceptibility profile is necessary. Moreover, alternative treatments could help in the fight against NTM- LD. a. The antimicrobial peptides (AMPs) could be effective against NTM V. NTM-LD treatment requires the administration of multiple antibiotics, however, few antibiotics show good activity. On the other side, even though drug susceptibility testing (DST) is performed individually, during treatment antibiotics are administered in combination. Furthermore, few studies have tested antibiotic combinations, and particularly triple-antibiotic combinations against NTM. b. The study of triple-antibiotic combinations could assess synergistic activity c. The adaptation of the time-kill assay to NTM could assess synergistic activity and determine the pharmacodynamics of antibiotics d. The adaptation of the macrophage infection model to NTM could assess synergistic activity and determine the intracellular activity of antibiotics VI. Biofilm formation plays an important role in NTM-LD by offering extra protection from antibiotics and other agents. Nonetheless, there is no standardized method for in vitro biofilm formation in NTM. Additionally, little is known about the activity of antibiotics and antibiofilm agents against NTM biofilm. e. The standardization of an in vitro model for biofilm formation could assess biofilm formation as well as determine the activity of antibiotics and antibiofilm agents against NTM biofilm |
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