Abstract：
Ninety-five years after Fleming\'s discovery of penicillin, a bounty of antibiotic compounds have been discovered, modified, or synthesised. Diversification of target sites, improved stability and altered activity spectra have enabled continued antibiotic efficacy, but overwhelming reliance and misuse has fuelled the global spread of antimicrobial resistance (AMR). An estimated 1.27 million deaths were attributable to antibiotic resistant bacteria in 2019, representing a major threat to modern medicine. Although antibiotics remain at the heart of strategies for treatment and control of bacterial diseases, the threat of AMR has reached catastrophic proportions urgently calling for fresh innovation. The last decade has been peppered with ground-breaking developments in genome sequencing, high throughput screening technologies and machine learning. These advances have opened new doors for bioprospecting for novel antimicrobials. They have also enabled more thorough exploration of complex and polymicrobial infections and interactions with the healthy microbiome. Using models of infection that more closely resemble the infection state in vivo, we are now beginning to measure the impacts of antimicrobial therapy on host/microbiota/pathogen interactions. However new approaches are needed for developing and standardising appropriate methods to measure efficacy of novel antimicrobial combinations in these contexts. A battery of promising new antimicrobials is now in various stages of development including co-administered inhibitors, phages, nanoparticles, immunotherapy, anti-biofilm and anti-virulence agents. These novel therapeutics need multidisciplinary collaboration and new ways of thinking to bring them into large scale clinical use.
摘要：
弗莱明发现青霉素95年后,发现了大量的抗生素化合物，已修改,或合成。目标站点的多样化，改善的稳定性和改变的活性谱使抗生素能够持续有效，但是压倒性的依赖和滥用助长了抗菌素耐药性（AMR）的全球传播。2019年，估计有127万人死于抗生素耐药细菌，这对现代医学构成了重大威胁。尽管抗生素仍然是治疗和控制细菌性疾病的核心，AMR的威胁已经达到灾难性的程度，迫切需要新的创新。在过去的十年里，基因组测序取得了突破性的进展，高通量筛选技术和机器学习。这些进展为新型抗菌剂的生物勘探打开了新的大门。它们还能够更彻底地探索复杂和多微生物感染以及与健康微生物组的相互作用。使用更接近体内感染状态的感染模型，我们现在开始测量抗菌治疗对宿主/微生物群/病原体相互作用的影响.然而,需要新的方法来开发和标准化合适的方法以测量在这些情况下的新型抗微生物组合的功效。一系列有前途的新型抗菌剂现在处于不同的开发阶段，包括共同施用的抑制剂，噬菌体,纳米粒子，免疫疗法，抗生物膜和抗毒剂。这些新的疗法需要多学科合作和新的思维方式来将它们带入大规模临床应用。
