2012 New Antibacterial Drug Discovery and Development Gordon Research Conference

描述(申请人提供)：本次戈登会议针对的是一个严重的国内和国际问题：缺乏治疗多重耐药细菌感染的新抗菌剂。在重症监护病房(ICU)和社区中，通常会导致严重感染的微生物已经对我们许多最有效的抗生素产生了抗药性。在社区中，肺炎链球菌等生物对内酰胺类抗生素的不敏感率超过20%。其他有效的药物，如大环内酯类，耐药率约为40%。社区获得性耐甲氧西林金黄色葡萄球菌在美国和全球的流行率呈爆炸性增长，在急诊室很常见。在ICU，MRSA约占所有金黄色葡萄球菌感染的50%，我们已经看到多重耐药革兰氏阴性菌的出现，因此即使是常见的病原体，如克雷伯氏菌和大肠杆菌，也可能携带超广谱内酰胺酶，使它们对我们许多最好的药物耐药，在KPC-内酰胺酶的情况下，这种耐药谱包括碳青霉烯类。在铜绿假单胞菌和不动杆菌的情况下，感染病原体对所有许可的抗生素都具有抗药性现在是相当常见的。临床绝望的一个衡量标准是，我们已经让有50年历史的相对有毒的药物(粘菌素/多合剂)死灰复燃，至少有一种可用的治疗干预措施。在这次戈登研究会议上，我们有一个独特的跨学科方法来解决这个问题，化学家、基础生物学家和转化科学家聚集在一起，工业界、学术界、监管机构和政治观察员都是利益相关者，并被邀请为交流做出贡献。我们过去的会议在科学上是严格和开放的，新科学的提出和确定这一进程中的瓶颈都是这一进程的一部分。我们有一个会议，我们致力于最广泛的参与，具体地说，我们希望将该领域的年轻成员纳入博士后水平，为正在审查的问题带来新的视角。会议地点非常适合这种交流，会议的结构遵循经典的戈登会议形式。选择讨论领导者的目的是为了在演讲后产生强有力的、有洞察力的讨论。这种形式是民主的，因此所有的声音都将被听到，重点将是展示最好和最新的科学并提出正确的问题来推动该领域的发展。在这项赠款申请中，我们要求提供部分财政支持，以支付与这项重要任务相关的费用。 与公共卫生相关：抗生素耐药性在全球普遍存在，给临床带来了日常挑战；然而，随着大型制药公司退出该领域，未来几代抗生素的发现和开发前景黯淡。多年来，已经没有新的革兰氏阴性抗生素类别，有效治疗革兰氏阳性细菌感染的前景也越来越渺茫。这场危机在国内和国际上都有影响，本次戈登研究会议的重点是将所有利益相关者聚集在一起，确定新抗菌剂发现和开发的最佳前进方向。

DESCRIPTION (provided by applicant): This Gordon Conference is aimed at a serious national and international problem: the lack of new antimicrobial agents for treatment of multi-resistant bacterial infections. In both the Intensive Care Unit (ICU) and the community, organisms commonly causing serious infections have become resistant to many of our most effective antibiotics. In the community, organisms such as Streptococcus pneumonia have a rate of non- susceptibility to ¿-lactam antibiotics exceeding 20%. Other effective agents, such as macrolides, have resistance rates on the order of 40%. Community-Acquired MRSA has exploded in prevalence across the United States and the globe and is commonly seen in emergency rooms. In the ICU, MRSA makes up approximately 50% of all Staphylococcus aureus infections and we have seen the advent of multi-resistant Gram-negative organisms, so that even common pathogens such as Klebsiella and E. coli may carry extended-spectrum ¿-lactamases, rendering them resistant to many of our best agents and, in the case of KPC ¿-lactamases, this resistance profile includes carbapenems. In the case of Pseudomonas aeruginosa and Acinetobacter species, it is now reasonably common for an infecting pathogen to be resistant to all licensed antibiotics. A measure of the clinical desperation is that we have resurrected 50-year old, relatively toxic agents (colistin/polymixins) to have at least one available therapeutic intervention. In this Gordon Research Conference, we have a unique cross-disciplinary approach to the problem, where chemists, basic biologists and translational scientists meet and where Industry, Academia, Regulatory Agencies and political observers are all stakeholders and are invited to contribute to the interchange. Our past meetings have been scientifically rigorous and open, with both new science coming forward and the identification of bottlenecks in the process being part of the process. We have a conference where we are dedicated to the broadest participation and, in specific, are desirous of inclusion of younger members of the field at the post-doctoral level, to bring fresh perspectives to the problems being examined. The site of the meeting is well-suited for this interchange and the structure of the conference follows the classical Gordon Conference format. The Discussion Leaders have been chosen with an eye toward generating robust, insightful discussion after the presentations. The format is democratic, so that all voices will be heard and the emphasis will be on presenting the best and newest science and asking the correct questions to push the field forward. In this grant application, we ask for partial financial support to defray the costs associated with this importan undertaking. PUBLIC HEALTH RELEVANCE: Antibiotic resistance is widespread globally, creating daily challenges clinically; yet prospects for discovery and development of future generations of antibiotics are bleak, as Big Pharma is exiting the field. There have been no new classes of Gram-negative antibiotics for many years and prospects for effective treatment of infections by Gram-positive bacteria are diminishing too. This crisis has national and international repercussions and it is the focus of this Gordon Research Conference to bring all the stakeholders together to identify the best way forward in the discovery and development of new antimicrobial agents.