Efeito de concentração subterapêutica de vancomicina sobre Staphylococcus aureus, no contexto do tratamento de bacteremias no paciente em hemodiálise
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Data
2016-06-20
Autores
Chagas, Rodrigo Altoé
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Universidade Federal do Espírito Santo
Resumo
In most patients undergoing hemodialysis treatment, due to the high rate of Staphylococcus aureus resistant to methicillin (MRSA) in bloodstream infections (BSI), vancomycin has been the antibiotic of choice for the empirical treatment of these infections. Failure in dose adjustment and drug dosing interval makes these patients often display a below therapeutic level (<10μg/mL) serum concentrations of vancomycin. The objective of this study was to investigate the effects of vancomycin subtherapeutic dose in some aspects of physiology and virulence factors of S. aureus. Strains of S. aureus with different susceptibility to vancomycin were exposed to subtherapeutic dose of the drug (<10mg / ml) to kill curve experiment. Then, the bacterial strains were cultured in the presence of drug for 5 consecutive days on Müller Hinton agar containing (0 a 10µg/mL), simulating the pattern empiric therapy of BSI in hemodialysis patients. Control cultures (without drug exposure) of the same bacterial strains were included in all experiments. At the end of the fifth day, the cultures were evaluated (i) for the minimum inhibitory concentration of vancomycin, daptomycin and oxacillin; (ii) biofilm production capacity and (iii) resistance to bactericidal activity of whole blood. In conclusion we reported that vancomycin overdose was not able to eliminat S. aureus and had limited effect against strains in exponential phase of growth. However, overdose of vancomycin has led to changes in the physiology of the microorganism as: (i) reduced susceptibility to vancomycin and daptomycin; (ii) increased resistance to the bactericidal action of the immune system and (iii) induction of a different response biofilm production among clinical isolates of S. aureus. These findings are consistent with therapeutic failure reports associated with underdosing vancomycin documented in the literature.
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Subtherapeutic dose , Hemodialysis , Bacterial virulence , Vancomycin , Vancomicina , Dose subterapêutica , S. aureus , Virulência bacteriana