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The global challenges presented by drug-resistant bacterial infections have stimulated much activity in finding new treatments. This review summarizes the progress and setbacks of non-traditional approaches intent on circumventing bacterial drug resistance. These approaches include targeting virulence via toxin production and virulence factor secretion, impeding bacterial adhesion to host cells and biofilm formation, interrupting or inhibiting bacterial communication, and downregulating virulence. Other strategies include immune evasion, microbiome-modifying therapies, and the employment of phages as treatments or carriers. Finally, the prospects of nanoparticles, immunotherapy, antisense RNA, and drug-resistance-modulation approaches are discussed. The development of non-traditional treatments suffers similar challenges faced by developers of conventional antibiotics; however, most of these new …