The urgent need for metallo-β-lactamase inhibitors: an unattended global threat.
The urgent need for metallo-β-lactamase inhibitors: an unattended global threat.
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DOI：
10.1016/s1473-3099(20)30868-9
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Bonomo RA
中科院分区：
文献类型：
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作者：
Mojica MF;Rossi MA;Vila AJ;Bonomo RA
由于其上级耐受性和有效性，β-内酰胺类抗生素是临床上最有效和处方最多的抗生素。对这些抗生素的耐药性的出现，主要是由于称为β-内酰胺酶的细菌酶的产生，已经通过引入β-内酰胺酶抑制剂而部分解决，β-内酰胺酶抑制剂恢复了原本过时的分子的活性。这种解决方案是有限的，因为目前可用的β-内酰胺酶抑制剂仅对丝氨酸β-内酰胺酶起作用，而金属β-内酰胺酶继续扩散、进化并赋予对所有β-内酰胺类（包括碳青霉烯类）的耐药性。此外，增加使用抗生素治疗重症COVID-19患者的继发性细菌性肺炎可能会加剧抗菌素耐药性问题。在这个个人观点中，我们总结了在这一研究领域取得的主要进展，强调了需要解决的主要挑战，以及在当前流行病中研究金属-B-内酰胺酶抑制剂的重要性。
Due to their superior tolerability and efficacy, β-lactams are the most potent and prescribed class of antibiotics in the clinic. The emergence of resistance to those antibiotics, mainly due to the production of bacterial enzymes called β-lactamases, has been partially solved by the introduction of β-lactamase inhibitors, which restore the activity of otherwise obsolete molecules. This solution is limited because currently available β-lactamase inhibitors only work against serine β-lactamases, whereas metallo-β-lactamases continue to spread, evolve, and confer resistance to all β-lactams, including carbapenems. Furthermore, the increased use of antibiotics to treat secondary bacterial pneumonia in severely sick patients with COVID-19 might exacerbate the problem of antimicrobial resistance. In this Personal View, we summarise the main advances accomplished in this area of research, emphasise the main challenges that need to be solved, and the importance of research on inhibitors for metallo-B-lactamases amidst the current pandemic.