Introduction: The drying up of antibiotic pipeline has necessitated the development of alternative therapeutic strategies to control the problem of antimicrobial resistance (AMR) that is expected to kill 10-million people annually by 2050. Newer therapeutic approaches address the shortcomings of traditional small-molecule antibiotics - the lack of specificity, evolvability, and susceptibility to mutation-based resistance. These 'non-traditional' molecules are biologicals having a complex structure and mode(s) of action that makes them resilient to resistance.
Areas covered: This review aims to provide information about the non-traditional drug development approaches to tackle the problem of antimicrobial resistance, from the pre-antibiotic era to the latest developments. We have covered the molecules under development in the clinic with literature sourced from reviewed scholarly articles, official company websites involved in innovation of concerned therapeutics, press releases from the regulatory bodies, and clinical trial databases.
Expert opinion: Formal introduction of non-traditional therapies in general practice can be quick and feasible only if supported with companion diagnostics and used in conjunction with established therapies. Owing to relatively higher development costs, non-traditional therapeutics require more funding as well as well as clarity in regulatory and clinical path. We are hopeful these issues are adequately addressed before AMR develops into a pandemic.
Keywords: Non-traditional; antibiotics; antibodies; antimicrobial resistance; microbiome engineering; peptides; phages; vaccines.