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Expert Opin Ther Targets. 2014 Aug;18(8):851-61. doi: 10.1517/14728222.2014.925881. Epub 2014 May 31.

Counteracting antibiotic resistance: breaking barriers among antibacterial strategies.

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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 ;



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.


antibiotic resistance; antimicrobial drugs; compartmentalized therapy; global risks; integrative therapy; multi-target therapy; public health

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