RESUMO
The widespread use of antibiotics created selective pressure for the emergence of strains that would persist despite antibiotic toxicity. The bacterial resistance mechanisms are several, with efflux pumps being one of the main ones. These pumps are membrane proteins with the function of removing antibiotics from the cell cytoplasm. Due to this importance, the aim of this work was to evaluate the inhibitory effect of tannic acid against efflux pumps expressed by the Staphylococcus aureus RN4220 and IS-58 strains. The efflux pump inhibition was assayed using a sub-inhibitory concentration of efflux pump standard inhibitors and tannic acid (MIC/8), observing their capacity to decrease the MIC of Ethidium bromide (EtBr) and antibiotics due the possible inhibitory effect of these substances. The MICs of EtBr and antibiotics were significantly different in the presence of tannic acid, indicating the inhibitory effect of this product against efflux pumps of both strains. These results indicate the possible usage of tannic acid asan inhibitor and an adjuvant in the antibiotic therapy against multidrug resistant bacteria (MDR).
Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Eritromicina/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Taninos/farmacologia , Tetraciclina/farmacologia , Antibacterianos/química , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana/genética , Eritromicina/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenótipo , Staphylococcus aureus/genética , Relação Estrutura-Atividade , Taninos/química , Tetraciclina/químicaRESUMO
The degradation products of the macrolide antibiotic erythromycin A (ERY) arising from direct ozone attack and hydroxyl radical attack are presented for the first time. Ozone treatment was carried out by spiking ozone stock solutions to solutions containing ERY-ERY:O3 = 1:5 and 1:10 (M:M), while, in parallel, t-BuOH was used as a hydroxyl radical (*OH) scavenger. The advanced oxidation processes (AOPs) O3/UV, O3/H2O2, and UV/H2O2 were carried out to recognize and verify possible differences between their primary degradation products; the initial concentrations were ERY:O3 = 1:5 (M:M), ERY:O3:H202 = 1:5:5 (M:M:M), or ERY:H202 = 1:5 (M:M), respectively. Six degradation products were identified from ozonation-one originates from direct ozone attack on the tertiary amine group, while the others arise from radical ion attack, which might be formed during degradation of O3 in water. Fewer primary degradation products were observed arising from *OH-based treatments (AOP) than from ozonation, possibly because the reaction of *OH radicals is non-selective and typically is diffusion-controlled. Four degradation products were detected by *OH radical attacks; two of them already were observed during ozonation, with one as an oxidized ERY molecule and the other as a non-oxidized fragment of the ERY molecule.
Assuntos
Eritromicina/química , Ozônio/química , Poluentes Químicos da Água/química , Estrutura Molecular , Oxirredução , Purificação da Água/métodosRESUMO
The agar diffusion method, widely used in antibiotic dosage, relates the diameter of the inhibition zone to the dose of the substance assayed. An experimental plan is proposed that may provide better results and an indication of the assay validity. The symmetric or balanced assays (2 x 2) as well as those with interpolation in standard curve (5 x 1) are the main designs used in the dosage of antibiotics. This study proposes an alternative experimental design for erythromycin microbiological assay with the evaluation of the validation parameters of the method referring to linearity, precision, and accuracy. The design proposed (3 x 1) uses 3 doses of standard and 1 dose of sample applied in a unique plate, aggregating the characteristics of the 2 x 2 and 5 x 1 assays. The method was validated for erythromycin microbiological assay through agar diffusion, revealing its adequacy to linearity, precision, and accuracy standards. Likewise, the statistical methods used demonstrated their accordance with the method concerning the parameters evaluated. The 3 x 1 design proved to be adequate for the dosage of erythromycin and thus a good alternative for erythromycin assay.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Técnicas de Química Analítica/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Eritromicina/farmacologia , Testes de Sensibilidade Microbiana/métodos , Bioensaio/métodos , Calibragem , Química Farmacêutica/métodos , Eritromicina/química , Micrococcus luteus/metabolismo , Modelos Estatísticos , Padrões de Referência , Reprodutibilidade dos Testes , Projetos de PesquisaRESUMO
O autor apresenta as perspectivas de progressos, no campo da terapêutica antimicrobiana, representadas pelo aparecimento de novos antibióticos macrolídicos com propriedades que os diferenciam, e muitas vezes os tornam mais atraentes, relativamente aos membros mais antigos da família. Compara esses novos antibióticos com a eritromicina, destacando as diferenças de propriedades farmacocinéticas e de espectro antimicrobiano. Por fim, apresenta as indicaçöes terapêuticas especiais que esses medicamentos poderäo vir a ter