Novas alternativas de reposicionamento de fármaco frente Acinetobacter baumannii multirresistente

Abstract

Bacterial resistance has relevant impacts on the health service. Complications related to hospital health care lead to increased length of stay, costs, morbidity, and mortality. Drug repositioning has been studied as an alternative for the treatment of infections caused by multi-resistant bacteria. The objective of this study was to evaluate the antimicrobial and antibiofilm activity of non-antibiotic drugs against the multidrug-resistant Acinetobacter baumannii clinic. The library of 234 drugs funded by the Food and Drug Administration (FDA) was acquired by Apex-Bio-. Microplate susceptibility tests advanced that 22 non-antibiotic drugs and 04 antibiotics inhibited more than 50% to 64 µg/mL-1 of bacterial growth of A. baumannii. Among these, the antihistamine desloratadine (with activity greater than 90% inhibition) was selected for the next experiments, due to its greater clinical safety and lower cost, when compared to other drugs. The combination study shows that desloratadine increases by twice the effectiveness of meropenem in inhibiting planktonic growth by eight times the effectiveness of desloratatine in inhibiting bacterial biofilm formation. In the bacterial death kinetics assay shown in 8 hours, the combination reduces approximately 100% of the bacterial load, when compared to desloratadine (reduces less than 10% of the bacterial load) and meropenem (does not reduce the bacterial load) alone. However, this combination effect was bacteriostatic after 16 hours. Scanning Electron Microscopy (SEM) images confirmed the results obtained, showing complete inhibition of the cellular integrity of bacterial growth A. baumannii under the interaction of the drugs desloratadine (0.5 µg. mL- 1 ) and meropenem (128 µg. mL-1 ). The in vivo infection model using the nematode Caenorhabditis elegans revealed that a combination of desloratadine and meropenem was able to protect 83% of infected nematodes against A. baumannii when compared to treatments using the compounds during. Our results indicate that desloratadine may be a safe and low-cost alternative to increase the activity of meropenem against clinicians who are multiresistant to this antibiotic. Thus, this antihistamine has the potential for antimicrobial and antibiofilm repositioning.