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抗生素耐药性:全球危机、问题与解决方案。

Antibiotic resistance: a global crisis, problems and solutions.

机构信息

School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA.

出版信息

Crit Rev Microbiol. 2024 Sep;50(5):896-921. doi: 10.1080/1040841X.2024.2313024. Epub 2024 Feb 21.

Abstract

Healthy state is priority in today's world which can be achieved using effective medicines. But due to overuse and misuse of antibiotics, a menace of resistance has increased in pathogenic microbes. World Health Organization (WHO) has announced ESKAPE pathogens (, spp.) as the top priority pathogens as these have developed resistance against certain antibiotics. To combat such a global issue, it is utmost important to identify novel therapeutic strategies/agents as an alternate to such antibiotics. To name certain antibiotic adjuvants including: inhibitors of beta-lactamase, efflux pumps and permeabilizers for outer membrane can potentially solve the antibiotic resistance problems. In this regard, inhibitors of lytic domain of lytic transglycosylases provide a novel way to not only act as an alternate to antibiotics but also capable of restoring the efficiency of previously resistant antibiotics. Further, use of bacteriophages is another promising strategy to deal with antibiotic resistant pathogens. Taking in consideration the alternatives of antibiotics, a green synthesis nanoparticle-based therapy exemplifies a good option to combat microbial resistance. As horizontal gene transfer (HGT) in bacteria facilitates the evolution of new resistance strains, therefore identifying the mechanism of resistance and development of inhibitors against it can be a novel approach to combat such problems. In our perspective, host-directed therapy (HDT) represents another promising strategy in combating antimicrobial resistance (AMR). This approach involves targeting specific factors within host cells that pathogens rely on for their survival, either through replication or persistence. As many new drugs are under clinical trials it is advisable that more clinical data and antimicrobial stewardship programs should be conducted to fully assess the clinical efficacy and safety of new therapeutic agents.

摘要

在当今世界,健康是首要任务,可以通过使用有效的药物来实现。但是,由于抗生素的过度使用和滥用,致病微生物的耐药性威胁已经增加。世界卫生组织 (WHO) 已将 ESKAPE 病原体(、 spp.)列为优先病原体,因为这些病原体已经对某些抗生素产生了耐药性。为了应对这一全球性问题,至关重要的是要确定新的治疗策略/药物作为抗生素的替代品。某些抗生素佐剂包括:β-内酰胺酶抑制剂、外膜流出泵和通透剂,可以潜在地解决抗生素耐药性问题。在这方面,溶菌酶裂解域抑制剂不仅为抗生素的替代品提供了一种新方法,而且还能够恢复先前耐药抗生素的效率。此外,噬菌体的使用是另一种有前途的策略,可以应对抗生素耐药性病原体。考虑到抗生素的替代品,基于纳米颗粒的绿色合成治疗方法是对抗微生物耐药性的一个不错选择。由于细菌中的水平基因转移 (HGT) 促进了新耐药菌株的进化,因此确定耐药机制并开发针对该机制的抑制剂可以成为对抗这些问题的一种新方法。在我们看来,宿主定向治疗 (HDT) 是对抗抗菌药物耐药性 (AMR) 的另一种有前途的策略。这种方法涉及针对宿主细胞内病原体生存所依赖的特定因素,无论是通过复制还是持续存在。由于许多新药正在临床试验中,建议进行更多的临床数据和抗菌药物管理计划,以充分评估新治疗药物的临床疗效和安全性。

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