Discovery and preclinical development of new antibiotics.
Discovery and preclinical development of new antibiotics.
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DOI：
10.3109/03009734.2014.896437
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发表时间：
2014-05
影响因子：
3.4
通讯作者：
Karlén A
中科院分区：
文献类型：
--
作者：
Hughes D;Karlén A
抗生素是我们这个时代的医学奇迹，但关键病原体之间日益频繁的耐药性使它们的有效性降低。如果这种趋势继续下去，对癌症患者、器官移植患者以及整个社会的后果可能是灾难性的。这个问题很复杂，涉及滥用和过度使用抗生素（选择耐药细菌的频率越来越高），以及缺乏对发现和开发的投资（导致几乎干燥的药物开发管道）。解决这一问题的补救办法应包括采取措施减少产生耐药性的选择性压力，并采取措施激励对抗生素发现和开发的新投资。将新的抗生素引入临床至关重要，因为这是目前唯一现实的治疗方法，可以确保许多医疗程序所需的感染控制水平。在这里，我们概述了一个复杂的过程，从最初发现一个命中分子，通过铅和候选药物的开发，到其进入I期临床试验的潜在的新型抗生素。成功的药物必须满足严格的标准，平衡体内对广谱病原体的高功效，对人类目标的责任最小，这解释了为什么即使有足够的投资，这个过程也容易失败。这强调了需要建立一个资金充足的抗生素发现和开发管道，以维持新型候选药物持续进入临床试验，以确保我们目前认为理所当然的先进医疗程序的维持。
Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted.
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影响因子：
3.2
作者：
Seeland, Swen;Toeroek, Michael;Huwyler, Joerg
通讯作者：
Huwyler, Joerg
影响因子：
56.3
作者：
Laxminarayan, Ramanan;Duse, Adriano;Cars, Otto
通讯作者：
Cars, Otto
影响因子：
4.9
作者：
Hernandez, Vincent;Crepin, Thibaut;Plattner, Jacob J.
通讯作者：
Plattner, Jacob J.
DOI：
10.3181/00379727-55-14461
发表时间：
1944-01-01
影响因子：
--
作者：
Schatz, A;Bugie, E;Waksman, SA
通讯作者：
Waksman, SA
影响因子：
14.2
作者：
Craig, WA
通讯作者：
Craig, WA