Antimicrobial growth promoter use in livestock: a requirement to understand their modes of action to develop effective alternatives

Antimicrobial agents (AMAs) have been used in agriculture since the 1950s as growth-promoting agents [antimicrobial growth promoters (AGPs)]. They have provided benefits to the agricultural industry by increasing production efficiencies and maximising livestock health, yet the potential risks surrounding resistance to AMAs in medically important pathogenic bacteria have enhanced public and government scrutiny regarding AMA use in agriculture. Although it is recognised that AGP administration can select for resistance to AMAs in enteric bacteria of livestock, conclusive evidence showing a link between resistant bacteria from livestock and human health is lacking (e.g. transmission of resistant zoonotic pathogens). Livestock production output must be increased significantly due to the increase in global population, and thus the identification of non-AMA alternatives to AGP use is required. One strategy employed to identify alternatives to AGPs is an observational empirical methodology, but this approach has failed to deliver effective alternatives. A second approach is aimed at understanding the mechanisms involved in AGP function and developing alternatives that mimic the physiological responses to AGPs. New evidence indicates that AGP function is more complex than merely affecting enteric bacterial populations, and AGPs likely function by directly or indirectly modulating host responses such as the immune system. As such, a more comprehensive understanding of the mechanisms associated with AMA function as AGPs will facilitate the development of effective alternatives. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.