Ramón y Cajal University Hospital, Ramón y Cajal Institute for Health Research (IRYCIS), Department of Microbiology, CIBERESP, and The Spanish Network for Research in Infectious Diseases (REIPI) , C. Colmenat km 9,100, 28034 Madrid , Spain +34 913368832 ; +32 913368809 ;
Expert Opin Ther Targets. 2014 Aug;18(8):851-61. doi: 10.1517/14728222.2014.925881. Epub 2014 May 31.
To fight against antibiotic resistance, prevention-only is no longer an acceptable strategy. The old concept 'one-infection, one-bug, one-drug', genocentrism in antibiotic discovery, and lack of integration between different antimicrobial strategies have probably contributed to current weaknesses in confronting antibiotic resistance. Resistance should be combatted in all fronts simultaneously, in the patient (complex therapy), the group (where resistance is maintained), and the significant environment (polluted by resistance).
This paper is reviewing why specific 'therapeutic' approaches are needed in each of these fronts, using different types of 'drugs' directed to a variety of targets, in the goal of inhibiting antibiotic resistant bacteria. Multi-target integrated combination strategies and therapies should be more extensively evaluated, not only in the infected patient (using novel formats for clinical trials), but as associations of 'therapeutic strategies' in the different compartments where antibiotic resistance emerges and flows (measuring global effects in resistance).
Multi-targeted therapeutic approaches require a relaxation of barriers among the various compounds, including systemic and topic antibiotics, antiseptics, biocides, anti-resistant clones vaccination, phages, decontamination products, and in general eco-evo drugs acting on factors influencing ecology and evolution of resistant bacteria. The application of methods of systems biology will facilitate such a multi-lateral attack to antibiotic resistance. Such advances should be paralleled by a simultaneous progress in regulatory sciences and close coordination among all stakeholders.
为了对抗抗生素耐药性,仅仅预防已经不再是一个可行的策略。旧的概念“一种感染,一种细菌,一种药物”、抗生素发现中的人类中心主义以及不同抗菌策略之间缺乏整合,可能导致了目前对抗抗生素耐药性的弱点。应该在所有方面同时对抗耐药性,包括患者(综合治疗)、群体(耐药性得以维持的地方)和重要环境(被耐药性污染的环境)。
本文探讨了为什么在这些方面中的每一个方面都需要特定的“治疗”方法,使用不同类型的“药物”针对各种目标,以抑制抗生素耐药细菌。多靶点综合联合策略和疗法应该更广泛地评估,不仅在感染患者中(使用新的临床试验形式),而且在抗生素耐药性出现和传播的不同环境中作为“治疗策略”的组合(测量耐药性方面的全球影响)。
多靶点治疗方法需要放宽各种化合物之间的障碍,包括全身和局部抗生素、防腐剂、杀菌剂、抗耐药克隆疫苗、噬菌体、去污产品,以及一般影响耐药细菌生态和进化的生态进化药物。系统生物学方法的应用将促进这种对抗生素耐药性的多方攻击。在监管科学方面取得同步进展并在所有利益相关者之间密切协调,应与这些进展并行。