Antibiotic failure: Beyond antimicrobial resistance

IF 15.8 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Cesar de la Fuente-Nunez , Angela Cesaro , Robert E.W. Hancock
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引用次数: 0

Abstract

Despite significant progress in antibiotic discovery, millions of lives are lost annually to infections. Surprisingly, the failure of antimicrobial treatments to effectively eliminate pathogens frequently cannot be attributed to genetically-encoded antibiotic resistance. This review aims to shed light on the fundamental mechanisms contributing to clinical scenarios where antimicrobial therapies are ineffective (i.e., antibiotic failure), emphasizing critical factors impacting this under-recognized issue. Explored aspects include biofilm formation and sepsis, as well as the underlying microbiome. Therapeutic strategies beyond antibiotics, are examined to address the dimensions and resolution of antibiotic failure, actively contributing to this persistent but escalating crisis. We discuss the clinical relevance of antibiotic failure beyond resistance, limited availability of therapies, potential of new antibiotics to be ineffective, and the urgent need for novel anti-infectives or host-directed therapies directly addressing antibiotic failure. Particularly noteworthy is multidrug adaptive resistance in biofilms that represent 65 % of infections, due to the lack of approved therapies. Sepsis, responsible for 19.7 % of all deaths (as well as severe COVID-19 deaths), is a further manifestation of this issue, since antibiotics are the primary frontline therapy, and yet 23 % of patients succumb to this condition.

抗生素失效:超越抗生素耐药性。
尽管抗生素的发现取得了重大进展,但每年仍有数百万人死于感染。令人惊讶的是,抗菌治疗未能有效消除病原体,这通常不能归因于基因编码的抗生素耐药性。这篇综述旨在阐明导致抗菌疗法无效(即抗生素失效)的临床情况的基本机制,强调影响这一未被充分认识的问题的关键因素。探索的方面包括生物膜的形成和败血症,以及潜在的微生物组。研究了抗生素之外的治疗策略,以解决抗生素失效的规模和解决方案,积极促成了这场持续但不断升级的危机。我们讨论了抗生素失效的临床相关性,包括耐药性、治疗的可用性有限、新抗生素无效的可能性,以及迫切需要新的抗感染药物或直接解决抗生素失效的宿主导向疗法。特别值得注意的是,由于缺乏批准的治疗方法,生物膜中的多药适应性耐药性占感染的65%。脓毒症导致19.7%的死亡(以及严重的新冠肺炎死亡),是这一问题的进一步表现,因为抗生素是主要的一线治疗方法,但23%的患者死于这种疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Drug Resistance Updates
Drug Resistance Updates 医学-药学
CiteScore
26.20
自引率
11.90%
发文量
32
审稿时长
29 days
期刊介绍: Drug Resistance Updates serves as a platform for publishing original research, commentary, and expert reviews on significant advancements in drug resistance related to infectious diseases and cancer. It encompasses diverse disciplines such as molecular biology, biochemistry, cell biology, pharmacology, microbiology, preclinical therapeutics, oncology, and clinical medicine. The journal addresses both basic research and clinical aspects of drug resistance, providing insights into novel drugs and strategies to overcome resistance. Original research articles are welcomed, and review articles are authored by leaders in the field by invitation. Articles are written by leaders in the field, in response to an invitation from the Editors, and are peer-reviewed prior to publication. Articles are clear, readable, and up-to-date, suitable for a multidisciplinary readership and include schematic diagrams and other illustrations conveying the major points of the article. The goal is to highlight recent areas of growth and put them in perspective. *Expert reviews in clinical and basic drug resistance research in oncology and infectious disease *Describes emerging technologies and therapies, particularly those that overcome drug resistance *Emphasises common themes in microbial and cancer research
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