Avaliação do perfil de sensibilidade de Klebsiella pneumoniae resistente aos carbapenêmicos e à polimixina B frente a polimixina B modificada pela complexação ao íon metálico cobre
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Data
2019-07-29
Autores
Vecchi, Rafael
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Universidade Estadual Paulista (Unesp)
Resumo
Devido ao crescente isolamento de espécimes de Klebsiella pneumoniae resistentes a praticamente todas as classes de drogas antimicrobianas, a busca por novas drogas que sejam alternativa terapêutica para o tratamento das infecções por eles causadas se torna relevante. Nesse contexto, a complexação de íons metálicos a drogas antimicrobianas é uma das abordagens empregadas, uma vez que é possível gerar novas drogas com atividade superior as drogas já existentes. No presente estudo, foi realizada a síntese de metalofármaco por reação de coordenação entre sulfato de polimixina B e cobre (II). O produto desta reação foi caracterizado e sua atividade antimicrobiana frente a espécimes de K. pneumoniae resistentes aos carbapenêmicos e à polimixina B foi avaliada. Os resultados demonstraram que as concentrações inibitórias mínimas (MIC) do complexo sintetizado foram menores em relação aos MICs de polimixina B para 44,44% dos espécimes avaliados; para 33,33% dos espécimes os MIC’s foram equivalentes, e para 22,23% dos espécimes os MIC’s do complexo foram superiores aos MIC’s da polimixina B. Esses resultados são promissores, uma vez que houve um incremento na atividade bacteriana da polimixina complexada ao metal para quase metade dos espécimes avaliados, mostrando que a síntese de novas drogas antimicrobianas através da complexação de íons metálicos é uma técnica que deve ser mais explorada. Além disso, nossos resultados devem conduzir a novos estudos que visem a melhor compreensão da estrutura, mecanismos de ação, toxicidade e atividade biológica, para determinar se o complexo gerado pode, de fato, ser uma alternativa terapêutica para o tratamento de infecções causadas por tais microrganismos multidroga-resistentes.
Due to the increasing isolation of Klebsiella pneumoniae specimens resistant to virtually all classes of antimicrobial drugs, the research for new drugs that are alternative therapeutics for the treatment of infections caused by them becomes relevant. In this context, the complexation of metal ions to antimicrobial drugs is one of the approaches used, since it is possible to generate new drugs with higher activity than existing drugs. In the present study, metallodrugs synthesis was performed by a coordination reaction between polymyxin B sulfate and copper (II). The product of this reaction was characterized and its antimicrobial activity against specimens of K. pneumoniae resistant to carbapenems and polymyxin B was evaluated. The results showed that the minimum inhibitory concentrations (MIC) of the synthesized complex were lower than the polymyxin B MICs for 44.44% of the evaluated specimens; for 33.33% of the specimens the MICs were equivalent, and for 22.23% of the specimens the MICs of the complex were superior to the MICs of polymyxin B. These results are encouraging, since there was an increase in the bacterial activity of metal complexed polymyxin for almost half of the evaluated specimens, showing that the synthesis of new antimicrobial drugs through the complexation of metallic ions is a technique that should be further explored. In addition, our results should lead to further studies aiming to a better understanding of the structure, mechanisms of action, toxicity and biological activity to determine if the complex generated may indeed be a therapeutic alternative for the treatment of infections caused by such multidrug-resistant microorganisms.
Due to the increasing isolation of Klebsiella pneumoniae specimens resistant to virtually all classes of antimicrobial drugs, the research for new drugs that are alternative therapeutics for the treatment of infections caused by them becomes relevant. In this context, the complexation of metal ions to antimicrobial drugs is one of the approaches used, since it is possible to generate new drugs with higher activity than existing drugs. In the present study, metallodrugs synthesis was performed by a coordination reaction between polymyxin B sulfate and copper (II). The product of this reaction was characterized and its antimicrobial activity against specimens of K. pneumoniae resistant to carbapenems and polymyxin B was evaluated. The results showed that the minimum inhibitory concentrations (MIC) of the synthesized complex were lower than the polymyxin B MICs for 44.44% of the evaluated specimens; for 33.33% of the specimens the MICs were equivalent, and for 22.23% of the specimens the MICs of the complex were superior to the MICs of polymyxin B. These results are encouraging, since there was an increase in the bacterial activity of metal complexed polymyxin for almost half of the evaluated specimens, showing that the synthesis of new antimicrobial drugs through the complexation of metallic ions is a technique that should be further explored. In addition, our results should lead to further studies aiming to a better understanding of the structure, mechanisms of action, toxicity and biological activity to determine if the complex generated may indeed be a therapeutic alternative for the treatment of infections caused by such multidrug-resistant microorganisms.
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Palavras-chave
polimixina B, complexo com cobre, Klebsiella pneumoniae, multirresistência, polymyxin B, copper complex, multidrug-resistance