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Métodos Terapêuticos e Terapias MTCI
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1.
ACS Infect Dis ; 6(3): 338-346, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-32017534

RESUMO

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.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Canabinoides/farmacologia , Cannabis/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Antibacterianos/química , Membrana Celular/efeitos dos fármacos , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Polimixina B/farmacologia , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/tratamento farmacológico
2.
Artigo em Inglês | MEDLINE | ID: mdl-29204272

RESUMO

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.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Burkholderia/tratamento farmacológico , Complexo Burkholderia cepacia/efeitos dos fármacos , Antibacterianos/farmacologia , Infecções por Burkholderia/etiologia , Infecções por Burkholderia/microbiologia , Complexo Burkholderia cepacia/isolamento & purificação , Fibrose Cística/complicações , Quimioterapia Combinada , Humanos , Testes de Sensibilidade Microbiana , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/etiologia
3.
Eur J Pharm Biopharm ; 79(1): 108-18, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21396444

RESUMO

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.


Assuntos
Antibacterianos/química , Anti-Infecciosos/química , Sistemas de Liberação de Medicamentos , Ácido Fusídico/química , Ácido Láctico/química , Ácido Poliglicólico/química , Polímeros/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Bactérias , Bandagens , Biofilmes/efeitos dos fármacos , Composição de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Ácido Fusídico/farmacocinética , Ácido Fusídico/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/metabolismo , Testes de Sensibilidade Microbiana , Nanofibras , Tamanho da Partícula , Plâncton/efeitos dos fármacos , Plâncton/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo , Propriedades de Superfície , Cicatrização/fisiologia , Infecção dos Ferimentos/microbiologia
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