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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Detalles Bibliográficos
Autor: Portell Buj, Elena
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
Descripción
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