Efeitos da prometazina sobre biofilmes de cocos gram positivos associados à endocardite infeccicosa

Abstract

Infectious endocarditis is a disease of the endothelial face of the cardiovascular structure, where the growth of vegetations composed of microbial biofilms, platelets and fibrin is observed. The most involved etiologic agents are Gram positive cocci, such as Streptococcus spp. and Staphylococcus spp. which are difficult to treat because they are in the form of biofilms. Therefore, it is necessary to study new compounds capable of defeating bacterial biofilms. Promethazine (PMZ), an efflux pump inhibitor of the phenothiazine family, has shown good results against biofilms of several microbial species. The present study aimed to evaluate the action of PMZ, isolated and associated with antimicrobials, on the dynamics of biofilm formation and maturation by Gram positive cocci associated with endocarditis, as well as to establish an ex vivo model of infectious endocarditis with fragments of porcine valves. For this purpose, 11 isolates were included, 4 Staphylococcus aureus, 4 S. epidermidis, 3 from S. mutans. The experiments followed the following steps: evaluation of the sensitivity of strains in planktonic form and biofilm for determination (CIM and CEMB), respectively, of PMZ and the antimicrobials vancomycin (VAN), oxacillin (OXA) and ceftriaxone (CRO); evaluation of the interaction of PMZ with antimicrobials using the Checkerboard method in planktonic form; investigation of the effect of PMZ on the formation and maintenance of mature biofilms; evaluation of PMZ combined with antimicrobials in the form of biofilms and, finally, to establish an ex vivo model of infective endocarditis. PMZ presented CIMs ranging from 97.65 - 195.31, from 24.4 - 97.65 and 97.65 - 195.31 μg / mL for S. aureus, S. epidermidis and S. mutans and CEMBs ranging from 781, 25 - 3,125 μg / m, respectively. PMZ associated with VAN in planktonic form, had a synergistic effect on all strains of S. mutans. The PMZ CIM reduced the biomass of biofilms in formation by 43% and in mature biofilm by 25%. When PMZ's MIC is combined with VAN's CEMB, there is a synergistic effect on all Staphylococcus spp. the same was repeated in the analysis of CIM of PMZ combined with CEMB of CRO, which had a synergistic effect on the three strains of S. mutans in the form of biofilm. The results demonstrate that ex vivo biofilms have more cells in 48h, defined as the best growth time. In this way, PMZ sensitizes biofilms of Gram positive coconuts to the antimicrobials used to treat infectious endocarditis, opening perspectives for the redirection of this drug and the ex vivo model presents a promising model bringing new possibilities for studies