Widespread excessive dispensing and irresponsible use of antibiotics has resulted in the development of resistant strains. Since the discovery of penicillin by Fleming in 1929, a large number of antibacterial agents have been developed and have had a huge impact on human health and the mortality rates of humans around the world. Throughout history, natural products have been utilized to treat a variety of diseases cinchona tree containing quinine to treat malaria, penicillin for the treatment of infectious diseases, and others. Another promising trend was by referring to nature to develop naturally derived agents with antibacterial activity on novel targets, agents such as bacteriophages, DCAP(2-((3-(3,6-dichloro-9 H-carbazol-9-yl)-2-hydroxypropyl)amino)-2(hydroxymethyl)propane1,3-diol, Odilorhabdins (ODLs), peptidic benzimidazoles, quorum sensing (QS) inhibitors, and metal-based antibacterial agents. Research efforts have been made to meet the urgent need for new treatments some have succeeded to yield activity against resistant Gram-negative bacteria by deactivating the mechanism of resistance, like the action of the β-lactamase Inhibitor antibiotic adjuvants. Several strategies have been reported to fight and control resistant Gram-negative bacteria, like the development of antimicrobial auxiliary agents, structural modification of existing antibiotics, and research into and the study of chemical structures with new mechanisms of action and novel targets that resistant bacteria are sensitive to. Due to their distinctive structure, Gram-negative bacteria are more resistant than Gram-positive bacteria, and cause significant morbidity and mortality worldwide. The majority of the WHO list is Gram-negative bacterial pathogens. In 2017, the World Health Organization (WHO) has published a list of antibiotic-resistant priority pathogens, pathogens which present a great threat to humans and to which new antibiotics are urgently needed the list is categorized according to the urgency of need for new antibiotics as critical, high, and medium priority, in order to guide and promote research and development of new antibiotics. Therefore, new antibacterial agents are crucially needed to overcome resistant bacteria. Some bacterial strains have acquired resistance to nearly all antibiotics. Antimicrobial resistance represents an enormous global health crisis and one of the most serious threats humans face today.
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