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Adv Drug Deliv Rev. 2014 Nov 30;78:14-27. doi: 10.1016/j.addr.2014.10.027. Epub 2014 Oct 28.

Therapeutic strategies to combat antibiotic resistance.

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Wasatch Microfluidics, Salt Lake City, UT 84112, USA.
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND58108, USA. Electronic address:


With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance.


Antibiotics; Antimicrobial polymers; Biofilm; Combination therapy; Nanoparticle delivery; Quorum sensing

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