Critically important antibiotics: criteria and approaches for measuring and reducing their use in food animal agriculture

Abstract

Globally, increasing acquired antimicrobial resistance among pathogenic bacteria presents an urgent challenge to human and animal health. As a result, significant efforts, such as the One Health Initiative, are underway to curtail and optimize the use of critically important antimicrobials for human medicine in all applications, including food animal production. This review discusses the rationale behind multiple and competing "critically important antimicrobial" lists and their contexts as created by international, regional, and national organizations; identifies discrepancies among these lists; and describes issues surrounding risk management recommendations that have been made by regulatory organizations on the use of antibiotics in food animal production. A more harmonized approach to defining criticality in its various contexts (e.g., for human versus animal health, enteric diseases versus other systemic infections, and direct versus indirect selection of resistance) is needed in order to identify shared contextual features, aid in their translation into risk management, and identify the best ways to maintain the health of food animals, all while keeping in mind the wider risks of antimicrobial resistance, environmental impacts, and animal welfare considerations.

Keywords: animal agriculture; antimicrobial resistance; antimicrobials; critically important antimicrobials.

Figure 1

WHO list (5th revision, 2017) of critically important antimicrobials for human medicine. Adapted from Ref. 36.

Figure 2

Domestic sales and distribution of antimicrobial drugs approved for use in food‐producing animals in 2016. Reproduced from U.S. FDA 2016 Summary Report. ¹Includes antimicrobial drug applications, which are approved and labeled for use in both food‐producing animals (e.g., cattle and swine) and nonfood‐producing animals (e.g., dogs and horses). ²kg = kilogram of active ingredient. Antimicrobials, which were reported in International Units (IU) (e.g., penicillins), were converted to kg. Antimicrobial class includes drugs of different molecular weights, with some drugs reported in different salt forms. ³Guidance for Industry #213 states that all antimicrobial drugs and their associated classes listed in Appendix A of FDA's Guidance for Industry #152 are considered “medically important” in human medical therapy. ⁴Not Medically Important refers to any antimicrobial class not listed in Appendix A of FDA's Guidance for Industry #152. ⁵NIR = Not Independently Reported. Antimicrobial classes for which there were fewer than three distinct sponsors actively marketing products domestically are not independently reported. These classes include the following: amphenicols, diaminopyrimidines, polymyxins, and streptogramins. ⁶NIR = Not Independently Reported. Antimicrobial classes for which there were fewer than three distinct sponsors are not independently reported. These classes include the following: aminocoumarins, glycolipids, orthosomycins, pleuromutilins, polypeptides, and quinoxalines.