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Métodos Terapéuticos y Terapias MTCI
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1.
ACS Infect Dis ; 6(3): 338-346, 2020 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-32017534

RESUMEN

The spread of antimicrobial resistance continues to be a priority health concern worldwide, necessitating the exploration of alternative therapies. Cannabis sativa has long been known to contain antibacterial cannabinoids, but their potential to address antibiotic resistance has only been superficially investigated. Here, we show that cannabinoids exhibit antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), inhibit its ability to form biofilms, and eradicate preformed biofilms and stationary phase cells persistent to antibiotics. We show that the mechanism of action of cannabigerol is through targeting the cytoplasmic membrane of Gram-positive bacteria and demonstrate in vivo efficacy of cannabigerol in a murine systemic infection model caused by MRSA. We also show that cannabinoids are effective against Gram-negative organisms whose outer membrane is permeabilized, where cannabigerol acts on the inner membrane. Finally, we demonstrate that cannabinoids work in combination with polymyxin B against multidrug resistant Gram-negative pathogens, revealing the broad-spectrum therapeutic potential for cannabinoids.


Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Cannabinoides/farmacología , Cannabis/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Animales , Antibacterianos/química , Membrana Celular/efectos de los fármacos , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana , Polimixina B/farmacología , Infecciones Estafilocócicas/sangre , Infecciones Estafilocócicas/tratamiento farmacológico
2.
Artículo en Inglés | MEDLINE | ID: mdl-29204272

RESUMEN

Effective strategies to manage Burkholderia cepacia complex (Bcc) infections in cystic fibrosis (CF) patients are lacking. We tested combinations of clinically available antibiotics and show that moxifloxacin-ceftazidime could inhibit 16 Bcc clinical isolates at physiologically achievable concentrations. Adding low dose of colistin improved the efficacy of the combo, especially at conditions mimicking CF respiratory secretions.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Burkholderia/tratamiento farmacológico , Complejo Burkholderia cepacia/efectos de los fármacos , Antibacterianos/farmacología , Infecciones por Burkholderia/etiología , Infecciones por Burkholderia/microbiología , Complejo Burkholderia cepacia/aislamiento & purificación , Fibrosis Quística/complicaciones , Quimioterapia Combinada , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/etiología
3.
Eur J Pharm Biopharm ; 79(1): 108-18, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21396444

RESUMEN

The structure and functions of polymer nanofibers as wound dressing materials have been well investigated over the last few years. However, during the healing process, nanofibrous mats are inevitably involved in dynamic interactions with the wound environment, an aspect not explored yet. Potential active participation of ultrafine fibers as wound dressing material in a dynamic interaction with wound bacteria has been examined using three wound bacterial strains and antimicrobial fusidic acid (FA)-loaded electrospun PLGA ultrafine fibers (UFs). These were developed and characterized for morphology and in-use pharmaceutical attributes. In vitro microbiological studies showed fast bacterial colonization of UFs and formation of a dense biofilm. Interestingly, bacterial stacks on UFs resulted in a remarkable enhancement of drug release, which was associated with detrimental changes in morphology of UFs in addition to a decrease in pH of their aqueous incubation medium. In turn, UFs by allowing progressively faster release of bioactive FA eradicated planktonic bacteria and considerably suppressed biofilm. Findings point out the risk of wound reinfection and microbial resistance upon using non-medicated or inadequately medicated bioresorbable fibrous wound dressings. Equally important, data strongly draw attention to the importance of characterizing drug delivery systems and establishing material-function relationships for biomedical applications under biorelevant conditions.


Asunto(s)
Antibacterianos/química , Antiinfecciosos/química , Sistemas de Liberación de Medicamentos , Ácido Fusídico/química , Ácido Láctico/química , Ácido Poliglicólico/química , Polímeros/química , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Bacterias , Vendajes , Biopelículas/efectos de los fármacos , Composición de Medicamentos , Evaluación Preclínica de Medicamentos , Ácido Fusídico/farmacocinética , Ácido Fusídico/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/metabolismo , Pruebas de Sensibilidad Microbiana , Nanofibras , Tamaño de la Partícula , Plancton/efectos de los fármacos , Plancton/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/metabolismo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/metabolismo , Propiedades de Superficie , Cicatrización de Heridas/fisiología , Infección de Heridas/microbiología
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